An essay commenting on the musical Bouncers by John Gober. Comments on the drama, effects and touching comedy.

An essay commenting on the musical Bouncers by John Gober. Comments on the drama, effects and touching comedy. JOHN GODBER'S "BOUNCERS" - SCRIPTED ASSESMENTBouncers - an ensemble by John Godber portrays lager-swilling lads, lipsticked, lacquered girls, all gyrating to the pulse of the dance floor; whilst out in the freezing cold skulk the ever watchful, ever ready, ever observant yet brutish bouncers - Lucky Eric, Jud, Les and Ralph. And so begins the journey into the secrets of a Friday night.John Godber along with "Bouncers" also wrote the acclaimed play "teechers". Two plays which require the actors to perform a variety of age, sex and stances; exploring the stage space with minimal props. Bouncers, set within the 1980s, explore themes such as stereotypes, prejudice and discrimination. Godber undermines this seriousness with comments such as "Lucky Eddie's first speech" or a chorus of "social comment". Beneath the comedy however, lies some very serious "social comment", not so much the voiced comment but the impression of the desperately empty lives of all the characters, male and female, bouncers and clubbers.English: Ralph Roister Doister, main character of ...Both plays are similar to each other, not just in staging but also in textual context.A favourable character throughout "Bouncers" was the character Les, also know as Kev and Cheryl. Kev I would describe as a stereotypical lad, not that bright with a fondness for lager. Les, a man of very little words and as for Cheryl, a clich ©d ditzy northern lass with a good heart.Each character was interesting in their own rightThe whole cast came across as very enthusiastic and portrayed a variety of ideas.The opening "Bouncers" introduced the lads and the girls, which smoothly ran into the opening scene at the hairdressers.With each character I saw a certain item that the audience could associate with. For example as Cheryl her top would be tied up, however as a bouncer...

Dreams essays

Dreams essays We all have dreams. They are our hopes and aspirations. We all dreams of something, whether it be growing up to be rich and famous, marrying that one person of our dreams, or anything else we wish to accomplish. Dreams are the pleasant images that pass through our mind during slumber. The bottom line is we all have dreams and one day we hope to accomplish them For the most part people believe the cliche that dreams do come true. Obviously everyone wants their dreams to come true, because we have this impression that dreams are supposed to be these wonderful and magical visions. When we have a bad dream, we give it a totally different name, we call it a nightmare. When we have a good dream, we do not have a separate name for that. So this gives dreams a positive connotation. Most people are fine with this, and do not think anything of it. The etymology of the word actually means something quite different. The word dream originates from a German word, which actually means to deceive or delude. It also has to do with ghost or apparition. Somewhere along the way the word changed from something that had negative connotation to a more peaceful and happy word. I do not believe that the phrase dream should keep its positive association with out having some negative side. What I find very strange is, the meaning of the German word that dream derives from is not found in any English dictionary today. It can only be found when searching for the etymology of the word. So dream used to have a semi-negative connotation and now it is very positive. I believe that the meaning of the word dream should not have been changed. It makes sense, dreams are something that are delusions. In reality most dreams do not come true. Yet we are raised to believe if you want it bad enough it will come. In my opinion that is bullshit. Ive had many realistic dreams, and worked hard at them, but most of the time nothing com ...

Four Questions 2 Assignment Example | Topics and Well Written Essays - 2000 words

Four Questions 2 - Assignment Example Essentially, it is these social coalitions that modify and determine the state ‘preferences’ or rather foreign policy in global politics at any moment in time. Political institutions form the basic channels through which these social interests of both individuals and civil society groups find their way into the political realm. The second basic assumption of liberalism is that the interdependence among of state preferences influence state behavior. Unlike realists who insists on constancy of preferences, liberalists hold that the state preferences are dynamic in nature and they play a critical role in influencing the world politics. The variations in state policy and behavior is a function of exact distribution of preferences and nature of the ‘stakes’ in consideration. States, as argued out by liberals, align their behavior to the exact nature of these preferences (compatible or conflictual) and their scope. A â€Å"social purpose† is a pre-requisite for any state to pay any attention to international matters, let alone trigger conflict, initiate cooperation, or consider any other crucial foreign policy undertaking. In the absence of this interdependence among the objectives of different states, a rational state will not engage in any international relations, hence exist as an isolated and autarkic entity. Basically, liberalists argue that conflictual goals promote political disputes whereas convergence of underlying preference form a platform for peaceful cooperation. Burchill (2009) describes liberalism as an optimistic approach to international relations that advocates for freedom, human rights, free market capitalism, and constitutionalism. Liberalists hold the fundamental belief that peace and freedom are the basic questions of domestic and international order. The recent trends in world politics has seen increased calls for nations to cooperate with international bodies for the mutual interest of global peace. In another example, United States has been undertaking solitary interventional actions in world affairs. However, with the advent of modern liberalism, calls to cooperate with multinational bodies such as NATO in conducting interventional plans has been on the increased. This is based evidenced in the recent French Military intervention in Mali and the NATO intervention in Libya. Liberalists advocate for the adherence to human rights and free market capitalism. China and U.S. offer examples of how liberalists’ perspectives of free trade is gradually permeating the international markets. China has recently expanded its market to the developing world especially in Africa. Most of its products are sold in these nations in exchange of other natural resources and agricultural produce. United States has equally expanded its trade across the globe. Nonetheless, China has come under sharp criticism from other players in the global economy for their engagements in activities that are thought to hinder free trade. WTO other nations continuously urge China to embrace the spirit of free and fair cooperation in trade. SECTION 2 Question A:. Identify and discuss at least three social, economic, and/or environmental activities of the UN and other intergovernmental organizations. Do you agree that each of these activities should fall under the realm of an organization such as the UN? Why or why not? Through international bodies such as International Monetary Fund (IMF) and World Bank, the United Nations plays a critical role in ensuring

(Book Proposal) Neurotheology in Review Essay Example | Topics and Well Written Essays - 2500 words

(Book Proposal) Neurotheology in Review - Essay Example Its primary objectives are to establish comprehensive, interdisciplinary approaches to understand beliefs and to explain, interpret and predict the influences of beliefs to thought, feeling, behavior and experience. The purpose of this volume is to provide scope and definition to the new discipline of Neurotheology. Current scholarship in Neurotheology offers perspectives from Darwinian evolution and neuroscience (studies in frontal, parietal lobes and temporal lobe epilepsy), neuropsychology, genetics, cognitive science, cellular biology, chemistry, physics, mindfulness, electromagnetic field effects, and varying perspectives from psychology like conditioning, attachment and learning theories. Other perspectives on science and beliefs are developing from neuroeconomics, neuropolitics, and neuroethics while other fields of science need greater inclusion like astronomy, ecology, engineering, geology, linguistics and mathematics. Neurotheology acknowledges the complexity and diversity of human beliefs by providing a broad conceptual framework to encompass beliefs whether mystical or religious, economic or environmental, political or social, or some other. Each dimension of beliefs affords critical, creative study of the science(s), beliefs and/or belief systems involved. Both the science and beliefs intersect through a four-fold methodology that provides the basis to unpack the complexity of their relationship and intimate the relationship’s influence to human thought, feeling, behavior and experience. The proposed book â€Å"Neurotheology† attempts to summarize the complexities of this science to provide a general understanding of what neurotheology is and investigate some of the diversity of disciplines to which it is applicable. The book is primarily intended for college students but will serve also as an introductory text for anyone interested in learning more about

Health Organization Essay Example | Topics and Well Written Essays - 750 words

Health Organization - Essay Example The healthy centre has been in existence since 1965 despite the numerous challenges that it faces. Saint Anthony centre for diabetes handles various cases that are related to nutrition, obesity, and metabolism. In addition, the hospital handles chronic conditions that affect diabetes patients. This paper will therefore analyse the marketing strategies of Saint Anthony’s hospital. The marketing mix (4 Ps) is one of the most common tools used to explain marketing phenomenon. The 4 Ps of marketing are products, place, price and promotion. The main product that the centre offers is treatment of diabetes and related complications. This is done through medication, or putting the patients (clients) on diet programs. The hospital also offers counselling services to patients with chronic conditions or those who are suffering from depression because of their ailments. Other products that the hospital offers are testing kits that are used by patients to test the level of sugars in their blood. Unlike other health organizations, saint Anthony diabetes centre offer comprehensive services to its customers. The hospital not only treats the medical condition by giving its patients control and regulation medications, but it offers counselling service to its patient. This is a critical aspect, since diabetes is a chronic disease that leaves its patients exposed to psychological depressions. The hospital has also enabled its patient to be able to monitor their health condition using the blood-sugar level test kits. This enables patients to monitor their health condition constantly without going to the health centre. Finally, the hospital offers its services in both English and Spanish. This has enabled the hospital to serve a wide range of customers. Saint Anthony serves its patient through its main centre in Chicago and other affiliated centres and clinics that are found in other major cities. In addition, the hospital has outreach programs that targets corporate and scho ols. Through the outreach programs, the hospital offers education on healthy nutrition and the significance of physical exercise. Price is a critical factor that affects the sustainability of business. The price of the products also determines the class of customers that a business attracts. The centre has compressive price strategies that cater for all its customers. The government and other organizations that are concerned with diabetes subsidize treatment for diabetic patients. Promotion involves informing the customers about the products offered by the business. The hospital markets its products through the media and field practice. Outreach programs in schools and corporate are some of the strategies that the hospital use to market its products. The centre mainly promote its services and products through partnership with schools and corporate. Relationship with these marketing partners is based on the special requirement of each of the marketing centres. For instance, a corpora te has requirements and expectations that are different from those of schools. In addition, the marketing collaborates benefits from the partnerships and the services offered by the centre. Affiliate schools use the partnership as a platform to promote healthy behaviours among their students. For instance, drug abuse and poor eating habits promote chronic conditions such as depression and cancer. These factors are also known to promote diabetes. Thus, schools consider this partnership as an opportunity to educate their students on healthy lifestyles. Similarly, the partnership benefits both the hospital and the corporate. Most professionals are faced with the challenge of balancing their professional life and social life leading to health complications. Corporate have the responsibility of ensuring that

The Connection Between Homelessness And Social Issues Social Work Essay

The Connection Between Homelessness And Social Issues Social Work Essay Essay Question What is the connection between homelessness, unemployment, drug use and mental illnesses in Australian society today? Unfortunately, in Australian society today, it is assumed that all Australians have access to a safe and secure environment, and are able to seek and gain employment; however this is not always the case for many Australians, with these social detriments being exacerbated by mental health issues and alcohol and drug abuse. However, in saying this not everyone that experiences one or more of these detriments necessarily experiences another. Alternatively, evidence has shown that there is an obvious link between each of these social and health detriments of health, with each intricately leading to another. This essay will discuss the intricate links between homelessness, unemployment, drug use and mental illness in todays society. On any given night in Australia it is estimated that over 100,000 people are homeless and living without essential human rights. (MHCA, 2009. p.5) While the reasons for peoples homelessness are varying, the abuse of alcohol, drugs and other harmful substances can exacerbate the situation and lead to further problems. The use of harmful substances by many homeless people is often seen as functional, this meaning that the use of these substances is helping them cope with their situation, and provide them with a sense of belonging in the Australian street culture. While many of the homeless people may start using soft drugs , this often opens the gateway to harder substances to which they can come completely reliant upon. The prevalence of heroin use in the homeless community is ten times higher than the general Australian community. (Australian National Council on Drugs, 2008) (Johnson Chamberlin, 2008, p.347) Australias homeless population, exhibit higher rates of emotional and physical health issues, anxiety, poor nutrition and difficulties in maintaining relationships (Lady Bowen Trust). 1 in 200 Australians in todays society dont have access to adequate housing and employment. It is estimated that 75 percent of this homeless population is suffering from some kind of mental illness, (MHCA, 2009, p.5) and that at least forty three percent engaged in substance abuse. (Johnson Chamberlin, 2008, p.347) A safe and secure environment is essential to physical and mental health. Mental health symptoms can often be worsened by unstable housing and social isolation. Homelessness significantly affects a persons ability to successfully maintain employment and relationships. When referring to mental illness, generally speaking it is an illness that has some kind of influence and effect on how a person, thinks, feels and acts. (MHCA, 2009, p.10) These can include mental health issues such as depression, anxiety personality disorders, schizophrenia and stress disorders. It is estimated that 1 in 5 people will experience a mental illness of varying degrees at some point in their lives. (MHCA, 2009, p.10) Although the exact cause of many mental illnesses are unknown, along with biological factors it is believed that environmental factors, stressful and abusing situations, substance or drug abuse and negative thought patterns all contribute to a persons mental health. Domestic violence, mental health, unemployment and substance abuse are among the leading causes of homelessness in Australia, along with critical shortages of affordable housing. However it is important to note that there are many contributing factors to a person becoming homeless such as family breakdown, sexual assault, gambling, mental illness, financial difficulties and social isolisation and broader social processes. (Homelessness Australia, 2010) Having a mental illness reduces a persons quality of life; the symptoms can make it difficult for individuals to cope with the daily demands of work and home life. In some cases this can lead to people becoming socially isolated, and even losing their jobs. This loss of employment often means people are no longer able to afford housing and a lack of social support can mean these people may become homeless. The unemployed are also less likely to receive medical treatment for symptoms of mental illness. If they do seek treatment of these illnesses they then face the problems of being able to pay for expensive prescriptions. (www.informahealthcare.com) The current economic climate has also placed increased stress on individuals and there has been a spike in Medicare claims for mental health consultations due to unemployment (Dragon, 2009). Studies have shown that homeless people have a higher prevalence of mental illness and substance abuse, with a Melbourne study showing 30 percent of homeless people surveyed had mental health issues and 43 percent suffered substance abuse issues. (MHCA, 2009, p.14) Substance abuse is also linked to homelessness, unemployment and mental illness, as substance abuse can take hold and damage a persons quality of life. Substance abuse begins to interfere with a individuals work and social life and this commonly leads to the destruction of relationships and loss of employment. Rather than this slide from positive relationships and employment being instant, many people tend to slide into homelessness as a result of their substance abuse. As they begin to come more dependent on these substances the transition becomes more rapid. ((Johnson Chamberlin, 2008, p.348) Having a mental illness can increase a persons likelihood of abusing drugs, which may in the short term make the symptoms of their mental illness feel better, while other peoples drug use can trigger the symptoms of mental illness. (MHCA, 2009, p.22) The link can also be made in terms of unemployment and homelessness, if a person is unemployed they can experience financial difficulties that can result in being homeless, alternatively if a person is homeless it becomes difficult to gain employment and break the cycle. The relationship between homelessness and substance abuse is well researched and documented; there is debate however on the direction of this relationship, and whether substance abuse is the cause or consequence of an individual becoming homeless. The focus of substance abuse as a consequence of homelessness is the social adaption model. Entering into homelessness often exposes individuals to a subculture where substance abuse is accepted and common place. This model also identifies that many people start to abuse substances as a method of coping with their situation, which can often be very stressful, uncertain and traumatic. (Johnson Chamberlin, 2008, p.343) Johnson and Chamberlain (2008, p.350) report that thirty four percent of individuals have engaged in substance abuse before becoming homeless, while sixty six percent first start abusing substances after becoming homeless.es as they struggle to pay for their addiction. Loss of employment then leads individuals looking for alternative income which can often lead to bad loans and illegal behaviours. (Johnson Chamberlin, 2008, p.p347-350) The social selection approach focuses on substance abuse as a cause of homelessness rather than a consequence. Substance abuse can be a leading factor into homelessness, as when a person becomes addicted to harmful substances they tend to start self damaging behaviours which affect social and work relationships. As their substance abuse increases, this often leads to financial difficulties and destruction of social networks. Psychological trauma and post traumatic stress disorder have been found to be contributing factors for many of the homeless population. There is no specific way in which each of these social detriments of health contributes to each other. For example, mental health issues may contribute or lead to people becoming homeless, while for others their mental health issues may be a result of being homeless or compounded by it. (MHCA, 2009, p.22) The homeless population can face discrimination when trying to find and apply for housing, especially when they have experienced a mental illness. (DHA, 2005) Many landlords are something about having people with a mental illness in their accommodation, due to the negative stigma that is attached with mental illness. Having a mental illness or past substance abuse problem can also follow a person and impact upon their lives even after they have overcome these issues. As in todays society many jobs and housing applications require police, credit and background checks. (MHCA, 2009, p.18) Webster (2007) reports that drug abusers with mental illnesses are likely to experience high rates of employment difficulties. Stating that individuals with mental illnesses have fewer work-related skills, poor interpersonal skills, impulse control and poor time management, therefore having less success in the workforce than individuals without mental illness and substance abuse issues. (Webster et al., 2007) Webster (2007) also reports that employment is a key factor in breaking the cycle of drug abuse, as employment occupies time, increases self esteem, promotes a sense of belonging and responsibility and provides structure. (Webster et al., 2007) In Australian society a quarter of the homeless population are children aged between 12 and 18, as these children age and mature they are at a higher risk of unemployment and being stuck in a vicious cycle of homelessness, unemployment, substance abuse and mental illness. (Graham, 2010, p.24) Children are more likely to face unemployment if they are from low socioeconomic status, left school early leading to low literacy and numeracy skills, are indigenous, live with one or more unemployed person, or live in remote areas. (Graham, 2010, p.20) A longitudinal study of Australian youth with mental health issues found that they did not suffer from mental health issues prior to unemployment. This shows the importance of employment and the effect that unemployment can have. (Graham, 2010, p.23) In 1991, Fischer Breakey developed three pathways into homelessness. The first being social selection which involves a breakdown in the capacity for living independently due to mental illness. The second pathway details socioeconomic adversity in which a person experiences unemployment, low levels of education and declining income. The third pathway described involves the inability to develop socially normative roles and support systems. (Kim Ford, 2010, p.40) The sociological imagination uses a sociological approach to analysing issues such as homelessness, substance abuse, unemployment and mental illness. This approach analyses associations of public issues and personal problems by looking at the Historical, structural, critical and cultural factors which contribute to a person experiencing issues such as homelessness. A better understanding of the causes can be found and thus leading to a better understanding of how to return to normal societal function and reducing the risk of relapse into past behaviours. . (Germov, 2009, p.7). The amount of structure and agency an individual holds in situations of homelessness, drug abuse, unemployment and mental illness is also important to note. The structure agency debate explores the amount of control a individual has over their behaviour and how much influence the social structure to which they belong plays. (Germov, 2009, p.7). Children that have grown up in an environment which is socioeconomically disadvantaged, high levels of drug abuse and unemployment, and poor work ethic, are more likely to follow in this pattern than children that have been brought up in higher socioeconomic conditions and have been instilled with a strong work ethic. Sue is 17 years of age and has been living away from home for two years, having left her family home due to conflict and violence with parents and physical assault between siblings. In the past two years Sue has lived a typically transient lifestyle, residing in crisis accommodation, various boarding arrangements and in an accommodation program to assist young people who are homeless and in need of specialist support. Sue has lived independently in a small unit as well as with a number of friends in their accommodation and in squats. Over the past two years Sue has engaged in self-harming behaviour and been violent and aggressive towards peers, herself and family, which has on occasion resulted in cautions from the legal system. Sue has also engaged in petty theft, auto-theft and break and enters, all resulting in legal cautions. Sue uses alcohol, marijuana and amphetamines and has been diagnosed with depression resulting in anti-depressants being prescribed (Mission Australia, 2005). In December 2008, the Australian Government released a White Paper on Homelessness: The Road Home: A National Approach to Reducing Homelessness. This paper recognises that maintaining the current approach to homelessness will see the homeless population of Australia significantly increase in the coming years. The paper takes a holistic view and aims to find solutions in address the varying needs of the homeless population, for example employment needs, education and training, health and social support. This report has three main initiative areas. They are to ensure that services intervene early to stop people becoming homeless, making services more connected and responsive across a range of areas not limited to housing, such as health and economic and social participation and strategies to assist people who become homeless to move quickly through the crisis system to stable housing, and providing the support they need so that they do not re-enter homelessness. Through the implementat ion on many straggles under these initiatives and 1.2 billion dollars in funding the Australian Government aims to have a fifty percent reduction in homelessness by 2020. (MHCA, 2009, pp.12-13) Todays society has negative stigma and labelling associated with homelessness. Due to this attributes, the skills they poses, their personality, past achievements are often disregarded and overrun by the fact they are homeless. (Mission Australia, 2005) As homelessness is not a social norm, it can be seen is deviant behaviour. With the rise of the medical model of health, importance is placed on the individual receiving treatment in order to restore health and conformity. (Roach Anleu, 2010, pp.242-260) Under the therapeutic model deviant individuals which can include the homeless, mentally ill, drug and alcohol abusers and those experiencing adjustment problems require psychiatric intervention, with little emphasis in the social and environmental conditions that contribute to these issues. (Roach Anleu, 2010, pp.242-260) Homelessness, unemployment, drug use and mental illness are all intricately connected in todays society. These social determinants of health all coexist and can each weigh largely upon another. These linkages can lead to a viscous cycle which can be hard to break. Conclusion What was discussed Reaffirm argument http://www.health.qld.gov.au/research_information/social_determinants.asp

Urban Legend of Ghostly Dreams :: Urban Legends

Ghostly Dreams of Owners Passed The following ghost story was told to me by a friend when I had a small group of friends over to my house in Massachusetts during spring break. He is a 20-year-old white male. The story was told at night after we had finished watching the show Lost on television, so the atmosphere was a little bit tense. It did not simply come up in context; I prompted all of my friends to tell any ghost stories or urban legends that they knew. I wrote the story down a few hours later after my friends left. This is as close to the story he told as I could remember at that time: My friend’s house is wicked old. Built in the 1700s, there’s a lot of really old stuff there. It may have been involved in the Underground Railroad. It has secret passageways and windows for servants to look in and talk to their masters. They originally lived in Springfield, Mass. and he [his friend’s Dad] knew the two people in the house in Agawam, Massachusetts previously. When he found out it was going on the market he decided to go buy it. Before they managed to complete the sale one of the two ladies died. And the other lady either died or left. At least one of them died in a room in the house. So after that they still decided to take the house. There were a few times when he tried to find things. And one time in particular he was looking for a ladder. He looked everywhere around the house including inside, outside, and in the shed. That night he had a dream and the dead previous owner came to him in the dream and told him to look in the shed aga in. The next day when he looked in the shed, the ladder was sitting right directly in the middle of it just like she had said in his dream. There was no way he could have missed it the day before. This happened on a couple different occasions with other items as well. As he told the story he used small hand motions to emphasize main points of the story and he paused after important points to allow the information to sink in; he did not sound nervous while telling the story, but he did try to convey a spooky atmosphere in an attempt to scare the audience.

Alkaloids Case Study Essay

Alkaloids are the most diverse group of secondary metabolites and over 5000 compounds are known. They are most commonly encountered in the plant kingdom, but representatives have been isolated from most other orders of organisms ranging from fungi to mammals. For years, there has been interest in their pharmacological activities, and for a long time selected plant products (containing alkaloids) have been used as poisons for hunting, murder, euthanasia, a euphoriants, psychedelics, and stimulants (e.g. morphine and cocaine) or as medicines (e.g. ephedrine). Many of our modern drugs now contain the same compound or synthetic analogues, and the pharmacological and toxicological properties of these compounds are thus of immense interest and importance. Almost two centuries have elapsed since Serturner isolated the first organic base clearly recognised as such, a crystalline substance that he obtained from the opium poppy, Papaver somniferum, and called morphine. The name alkaloid is applied to the members of a class of natural products of basic nature, and is derived from the name â€Å"vegetable alkali† first applied to these substances. They all owe their basic nature to an amino nitrogen. It is more difficult than at first might be supposed to define the term alkaloid. The work was coined in 1818 by Meissner and implies a compound similar to an alkali, referring to the basic properties of this class of substance. Meyer’s Konversations- Lexikon of 1896 states, â€Å"Alkaloids (plant bases) occur characteristically in plants and are frequently distinguished by their remarkable physiological activity. They contain carbon, hydrogen and nitrogen and in most cases oxygen as well; in many cases they resemble the alkalisà ¢â‚¬ . Modern dictionary definitions only differ in minor details from those of the older nontechnical literature. A definition due to Pelletier in 1982 includes cyclic nitrogen- containing molecules which are true secondary metabolites (i.e. of limited occurrence and produced by living organisms. Simple acyclic derivatives of ammonia and simple amines are thus excluded, and the additional requirement, that the nitrogen atom must have a negative oxidation state, excludes nitro and nitroso compounds. As for other natural products, no uniform system of nomenclature has so far been devised for alkaloids. In most cases the name of the alkaloid has been derived from the plant name. Thus, papaverine was called after the Papaver species from which it was isolated. The names cocaine (from Erythoxylum coca) and atropine (from Atropa belladonna) are other examples. Frequently several alkaloids are obtained from the same plant, and the names devised for them will depend on the inspiration of the natural products chemist who isolated them. Alkaloids as a class have interested organic chemists partly on account of their physiological action on the animal organism, and partly on account of the complex structural and synthetical puzzles that they pose. The chemistry of the alkaloids is but a branch of the wide chemistry of nitrogenous heterocyclic compounds, but the methods by which the structures of individual bases are deduced from degradative evidence and confirmed by total synthesis are typical of the methods applied for these purposes whole field the chemistry of natural products are illustrative of the general fundamental principles of organic chemistry. Structural types Alkaloids are usually classified according to the amino acids (or their derivatives) from which they arise. Thus, the most important classes are derived from the following Amino acids: * Ornithine and Lysine * Aromatic amino acid phenylalanine and tyrosine * Tryptophan and a moiety of mevalonoid origin Also a number of compounds are also derived from: * Anthranilic acid * Nicotinic acid This classification however, fails to include the alkaloids derived from a polyketide or a terpenoid, with the incorporation of a nitrogen atom, ultimately from ammonia. Examples are Conine and batrachotoxin which are often known as ‘pseudoalkaloids’. Other compounds covered by Pelletier’s definition also exist. Examples are the antibiotic cycloserine, mitomycin C, mushroom toxin muscimol and the purine alkaloids such as caffeine. There is another classification of the alkaloids according to the location of the nitrogen atom in certain structural features: 1. Heterocyclic alkaloids 2. Alkaloids with exocyclic nitrogen and aliphatic amines 3. Putrescine, spermidine and spermine alkaloids 4. Peptide alkaloids 5. Terpene and steroidal alkaloids Classifying the whole range of alkaloids according to this system result in them being dividing them up unequally as the great majority fall into the heterocyclis group and the smallest group is the putrescine, spermidine and spermine alkaloids. Occurrence Of the more than 5000 alkaloids known, most occur in flowering plants, although the distribution is far from uniform. Thus, although 40% of all plant families have at least one species containing alkaloids, when the 10000 plant genera are considered, only about 9% of these have been shown to produce alkaloids. Increasing numbers of alkaloids have been isolated from animals, insects, and microorganisms. Although mammalian alkaloids are rare, two examples are (-)-castoramine (a) from the Canadian beaver; and muscopyridine (b) from the musk deer. Both compound have a role in communication as territorial marker substances. Insects produce a variety of structural types which include the 2,6- dialkylpiperidines of the fire ant (c), the tricyclic N-oxides of the ladybird (d) and the quinazolines of the European milliped (e). Tese compounds are used for defence. During the last three decades Marine organisms have been investigated. Amongst the alkaloids are the exceedingly complex Saxitoxin (f) produced by a red coloured dinoflagellate. The ‘red tides’ contain mass aggregations of such organisms, and food poisoning when he toxic alkaloids are passed along the food chain to man. The Japanese puffer fish is highly valued as a culinary delicacy, but it is hazardous because its liver and ovaries contain the highly toxic tetrodotoxin. Fungi also produce alkaloids, and these too, present potential hazards as food contaminants. The ergot alkaloids, for example, Chanoclavine (g) produced by the fungus Claviceps purpurea, were a frequent soure of misery and death during the Middle Ages through the contamination of rye bread. Some of these were neurotoxic whilst others caused vasocontriction. During the last 40 years most of these non plant alkaloids have been isolated and their structures elucidated. The introduction of modern chromatographic and spectroscopic techniques facilitated this. Isolation Work on the constitution of alkaloids is often prefaced by the problem of their isolation from plant material or from residues after commercially important constituents have been removed. The isolation of each alkaloid is an individual problem there are a variety of procedures which may be entitled to generic rank. There are few plants which produce a single alkaloid so the main problem is the separation of mixtures. Many alkaloids are basic and occur as salts of 2-hydroxybutane-1, 4-dioic acid (malic acid), or of 1,3,4,5-tetrahydroxycyclohexane (quinic acid). They can thus be extracted into acid solution using aqueous hydrochloric, tartaric, or citric acids. Neutral alkaloids such as colchicines or piperine, which are in fact amides, remain in the organic phase, whilst most other alkaloids are isolated after basification and extraction into ethyl acetate. Steam distillation can be used also be used with low molecular weight alkaloids; but almost invariably sudsequent purification of the crude alkaloid mixtures is effected by chromatography using silica or alumina, and then recrystallisation of the partially purified compounds from solvent systems like aqueous ethanol, methanol/chloroform, or methanol/acetone. Structure elucidation Classical era: The classical era for structural studies on alkaloids was the 19th Century, though this could be extended to the 1930’s (advent of x-ray crystallography) or even to the 1970’s (advent of high resolution NMR facilities and modern methods of mass spectroscopy. Two case histories will be discussed, those of morphine and atropine. Opium has been used by man for thousands of years, so it is not suprising that the major active ingedient, morphine, was the first alkaloid to be isolated in pure state (by Serturner in 1805). It was not until 1923 that Sir Robert Robinson established the stucture of morphine. Chemical evidence for the structure is as follows: Standard showed that the nitrogen atom was fully substituted, and that the phenolic hydroxyl was present as it gave a positive FeCl3 test. Two hydoxyls were present as a diacetate and dibenzoate could be formed. Both compounds contained one olefinic double bond as codeine absorbed one. It was found that a reduced phenanthrene with a two-carbon bridge containing a tertiary nitrogen atom (with methyl as on substituent) was present, and the structure of morphine and codeine were first proposed in 1923 and 1925 respectively by Robinson and Gulland. Synthesis of morphine was carried out in 1956 by Gates. Atropine on the other hand, is not generally a natural product but arises through racemisation of (-)-hyoscyamine (see (a) below) and purification, and is thus ( )-hyoscyamine. (-)-hyoscyamine is the most common tropane alkaloid. In 1833 atropine was isolated from Atropa belladonna. Hydrolysis with warm barium hydroxide solution produced racemic tropic acid and tropine. Degradative studies and then through synthesis found the structure of tropic acid: Exhaustive degradation of tropine, carried out by Willstlter between 1985 and 1901, provided evidence for the bicyclic structure of tropine. The most widely used process in degradative studies of alaloids is exhaustive methylation, known as Hofmann degradeation. . This involves the pyrolysis of a quaternary ammonium hydroxide to form and olefin an a tertiary base: To ensure the complete removal of the nitrogen atom when it constitutes part of a ring, two degrdations must be carried out. When exhaustive methylation of of cyclic compounds might be expected to give 1,4-dienes, the alkaline conditions of the reaction may result in the migration of one of the double bonds to give a 1,3-diene. For example, the exhaustive methylation of N-methylpiperidine gives 1,3-pentadiene (piperylene) and not 1,4-pentadiene. The diene is then easily hydrogenated to form a saturated hydrocarbon. If Hofmann degradation fails to bring about ring fission of cyclic amines, Emde degradation, invoving catalytic reduction of a quaternary salt by sodium amalgam or sodium in liquid ammonia, may be applied. For example, attempted Hofmann degradation of N-methyltetrahydroquinoline methoxide results in regeneration of the parent base, while Emde reduction with sodium amalgam affords the ring-opened amine. Alkaloids containing diphenyl ether linkages, for example, bis-benzylisoquinoline, are cleaved into two fragments by reduction with sodium in liquid ammonia. For example, the structure of the alkaloid dauricine was established by reductive cleavage of O-methyl-dauricine. Modern era: During the last 30 years, structure elucidation has benn facilitated by the use of mass spectroscopy, and 1H and 13C NMR techniques. It is now possible to determine the structure in days with a few milligrams or less of pure compound. It took 118 years to determine the structure of morphine. The mass spectrum data for morphine is highly informative and is shown below and would have helped enormously years ago. Once the structure of an alkaloid is known, partial or total synthesis can be attempted. Biosynthesis It is possible to determine the amino acid from which an alkaloid is derived just by looking at the structure. Before availability of radio-isotopes 14C and tritium, and more recently the stable isotopes 13C and 15N it was only possible to speculate about the likely biosynthetic pathways. This was sometimes successful as for example, the suggested pathway to the isoquinoline alkaloid is as follows: It is possible to divide the biosynthesis of the alkaloids into two categories according to whether products are obtained from the amino acids ornithine and lysine, or the aromatic amino acids phenylalanine, tyrosine, tryptophan. Alkaloids derived from ornithine and lysine: Pyrrolidine alkaloids – hygrine, cocaine, tropinone, hyoscyamine etc Piperidine alkaoids – piperine, (-)-lobeline etc Quinolizidine alkaloids – sparteine, cytosine, (-)-lupinine etc Pyridine alkaloids – nicotine, anabasine, anatabine etc Alkaloids derived from phenylalanine and tyrosine: Monocyclic compounds – hordenine etc Tetrahydroisoquinoline alkaloids – morphine, codeine, thebaine, noscapine (narcotine), papaverine, heroin etc Alkaloids derived from tryptophan: Simple indole derivatives: psilocybin, dimethyltryptamine, physostigmine etc Complex indole derivatives : harmaline, echinulin, ergonovine etc No class of naturally occurring organic substances shows such an enormous range of structures as the alkaloids with over 5000 known. It would be impossible to discuss each one of these within the time limit. Therefore, this project is concerned with the following alkaloids: Morphine ( including codeine and heroin), Cocaine, Nicotine and Caffeine (including theophylline). These alkaloids are present in enormous quantities in the world and seem appropriate to be discussed due to the current interest in their effects particularly when used illegally. They are some of the most well known alkaloids. Morphine (Codeine and Heroin) When the unripe seed capsules of the opium poppy, Papaver somniferum, is cut or pricked, a viscous liquid is exuded. After the exudates dries and darkens with exposure to air, a hard but still partly sticky mass is obtained. This is opium, which has been used for many centuries by some for medicinal purposes. Opium is important as a painkilling drug in its own right, but is also the source of other analgesic drugs such as morphine and heroin. Mankind had discovered the use of opium by the time of the earliest written records. In fact, the first recorded use of opium as a painkiller was around 6000 years ago by the Sumerians, and the Babylonian and Egyptian writings contain many references to the value of opium preparations for the relief of pain. Thomas Sydenham, the 17th Century pioneer of English medicine wrote, â€Å"Among the remedies which it has pleased Almighty God to give to man to relieve its sufferings, none is so universal and so efficacious as opium†. Nowadays, alt hough opium is no longer regareded as a universal analgesic, it is still a very important source of morphine. The pharmacologically active constituents of opium have been employed in medicine for many thousand of years. During the 19th century these constituents were isolated as pure chemical entities. Morphine is a naturally occurring substance and is the major constituent of opium, constituting about 10% (sometimes up to 20%) of its weight. Morphine was first isolated in 1805 by Friedrich Sertrner. However, its basic structure was not correctly determined until 120 years later. Morphine provides symptomatic relief of moderately severe to severe pain. Morphine acts as an anesthetic without decreasing consciousness, and it is one of the most powerful analgesics known. However, it also suppresses the repiratory system, and high doses can cause death by respiratory failure. Its analgesic properties are related to the ability of the molecule to fit into and block a specific sit on a nerve cell. This eliminates the action of the pain receptor Cocaine Cocaine is obtained from coca leaves (Erythryloxum coca) and has the formula C17H23O4N and a molecular weight of 303.39. The anaesthetic properties of cocaine were first recognised by Koller in 1882, but it has now been largely replaced in the clinic by synthetic analogues due to its widespread abuse as a narcotic. It is, however, still much used as a stimulant by Andean Indians. After chewing the leaves, they are easily fatigued and can go on for long periods without food. Cocaine is shipped and sold in the form of the water-soluble hydrochloride salt, which may be ingested through the nasal passages by ‘snorting’ orally and intravenously. There are severe physical and psychological side effects of the drug, such as brain seizures, respiratory collapse, heart attack, paranoia, and depression. Cocaine may be hydrolysed by acids or alkalis to methyl alcohol, benzoic acid, and (-)-ecgonine, C9H15O3 N; only partial hydrolysis, to benzoyl- (-)-ecgonine, C16 H19O4 N, and methyl alcohol when the alkaloid is boiled with water. Cocaine can be regarded as being derived from ornithine. Willsttter worked on a tortuous synthesis (of about 20 steps) of tropinone between 1900 and 1903, but in 1917 Robinson reported his ‘one-pot’ synthesis and also provided what was probably the first example of a formal retrosynthetic analysis. He stated: ‘By imaginary hydrolysis at the points indicated by the dotted lines, the substance may be resolved into succinaldehyde, methylamine and acetone’. The yield of this reaction was poor but Schpf and Lehmann reported optimised conditions (buffered solution at pH5 and 25C) which allowed 85% yield. A variety of mechanisms are possible and the one shown below envisages a reaction between the enol form of acetone dicarboxylate and the condensation product from succinaldehyde and methylamine. Willsttter made his own contributions based on this type of chemistry, and completed simple synthesis of tropinone in 1921 and a synthesis of cocaine in 1923. The synthesis of cocaine is as follows: A Robinson- type reaction yielded the expected azabicyclo structure but with a fortuitous axial stereochemistry for the carbomethoxyl group. Racemic cocaine was formed after separation of the diastereoisomeric products on the reduction of the ketone and benzoylation of the mixture of alcohols. An important aspect of Robinson’s route is that it represented the first biomimetic synthesis of an alkaloid. He provided inspiration for others to consider possible biosynthetic pathways, before planning their synthetic routes to alkaloids. Nicotine Nicotine, present in dried tobacco leaves of the plant nicotiana tabacum in 2-8% concentration, is the active ingredient in cigarettes and other tobacco products. The reason tobacco is used by so many people is because it contains this powerful drug nicotine. When tobacco is smoked, nicotine is absorbed by the lungs and quickly moves into the bloodstream, where it is circulated throughout the brain. All of this happens very rapidly. In fact, nicotine reaches the brain within 8 seconds after someone inhales tobacco smoke. Nicotine can also enter the blood stream through the mucous membranes that line the mouth or nose, or even through the skin. Smoking and chewing tobacco have been connected to heart and lung disease and cancer, mainly a result of the presence of carcinogens, carbon monoxide and other toxins. Nicotine affects the entire body. Nicotine acts directly on the heart to change heart rate and blood pressure. It also acts on the nerves that control respiration to change breathing patterns. In high concentration, nicotine is deadly. In fact, one drop of purified nicotine on the tongue will kill a person. It’s so lethal that it has been used as a pesticide for centuries. So why do people smoke? The mode of action of nicotine is complex. Ingestion of the molecule may stimulate or calm the user and it may affect his or her mood, appetite, and cognition. There appears to be little doubt that nicotine is an addictive drug, and the debate about how to regulate its availability is ongoing. Nicotine is part of the pyridine alkaloids and is the chief alkaloid of tobacco. It can therefore be classed as a tobacco alkaloid. Nicotine has the empirical formula C10 H14 N2, a molecular weight of 162.26 and was first observed by Vanquelin in 1809 and isolated 19 years later by Posselt and Reimann. Its structure is as follows: It is a colourless liquid with a boiling point of 246.1-246.2C and is miscible in all proportions with water below 60 and above 210. It is less soluble between these temperatures. When oxidised with chromic acid it yields an amino acid, C6H5O2N, which may be decarboxylated to pyridine–carboxylic acid. Nicotine is therefore a 3-substituted pyridine and that the substituent is a saturated group containing five carbon atoms and one nitrogen atom. The alkaloid forms a crystalline addition compound with zinc chloride, and when this is heated with lime pyridine, pyrrole and methylamine are obtained, suggesting that the structure be as above (1). This was supported by the degradation of the alkaloid to N-methylproline (1) to (5) (below), the oxidation of dibromocotinine (6) to nicotinc acid, malonic acid and methylamine (6) to (7). Also, by the reductive hydrolysis of bromocotinine to methylamine and the dihydroxy-acid (8). The structure of nicotine was finally confirmed by synthesis. Three syntheses of nicotine have been recorded. The first was based on the discovery that N-acetylpyrrole is transformed by heat to C-acetylpyrrole shown to be ?-acetylpyrrole. Pictet and Crepieux applied this reaction to N- pyridylpyrrole (3) (below) obtained by the reaction of -aminopyridine1 with mucic acid (2). The compound 31- pyridyl-2-pyrrole (4) was formed. An attempt to methylate the pyrrole nitrogen by heating the potassium derivative with yielded (5) (methiodide of 31- pyridyl-N-methyl-2-pyrrole). Distillation of this with calcium oxide gave nicotyrine (6). Selective hydrogenation of the pyrrole nucleus with a palladium-carbon catalyst converted nicotyrine (6) to nicotine with about a 25% yield. PICTET’S SYNTHESIS: Pictet’s classical synthesis involves two steps at high temperatures, one of which is a rearrangement. It cannot therefore be regarded as unambiguous. However, a second synthesis by Spth and Bretschneider involves no rearrangement at high temperature and are thus structurally specific. SPATH’S SYNTHESIS: (1) (Above) was converted into (2) via electrolytic reduction, which on treatment with potassium and methyl sulphate gave (3) (N-methylpyrrolidone). Ethyl nicotinate was then condensed with (3) in the presence of sodium ethanoate and the resulting -pyridyl-1- -(N1 – methyl-?1- pyrrolidonyl) – ketone (4) was hydrolysed with fuming hydrochloric acid at 130. The derived amino ketone (5) was reduced with zinc and sodium hydroxide to the corresponding alcohol (6), which was converted to nicotine on treatment with hydrogen iodide and potassium hydroxide. A third synthesis of nicotine by Craig was also carried out: CRAIG’S SYNTHESIS: Nicotinonitrile (1) (above) was reacted with ?- ethoxypropylmagnesium bromide. The product of the reaction (2) (3-pyridyl-?-ethoxypropylketone) formed an oxime (3), which was reduced to an amino derivative (4). On heating to 150-155 with 48% hydrobromic acid this was converted to nornicotine (5), which in turn was methylated to nicotine. The pyridine ring in nicotine is derived from nicotine acid, which itself is derived from aspartic acid and glyceraldehyde-3- phosphate: The remaining steps en route to nicotine are shown below: Caffeine The purine system occurs widely in nature. Two purines, adenine and guanine, are constituents of the nucleic acids; adenine is a component of coenzymes I and II, of flavin adenine dinucleotide and of adenosine with 3 distinguished compounds: caffeine, theophylline and theobromine. They are physiologically active constituents of coffee, cocoa, and tea. The compounds have different biochemical effects, and are present in different ratios in different plant sources. These compounds are very similar and differ only by the presence of methyl groups in two positions of chemical structure as shown below: They are easily oxidised to uric acid and other methyluric acids, which are also similar in chemical stucture. CAFFEINE – 1,3,7- trimethylxanthine SOURCES – Coffee, tea, cola nuts, mate, guarana EFFECTS – Stimulant of the central nervous system, cardiac muscle and respiratory system, diuretic, delays fatigue. THEOPHYLLINE – 1,3 – dimethylxanthine SOURCES – Tea EFFECTS – Cardiac stimulant, smooth muscle relaxant, diuretic, vasodilator. THEOBROMINE – 3,7- dimethylxanthine SOURCES – Principle alkaloid of the cocoa bean (1.5-3%), cola nuts and tea. EFFECTS – Diuretic, smooth muscle relaxant, cardiac stimulant, vasodilator. Theophylline has a stronger effect on heart and breathing than caffeine. For this reason it is the drug of choice in home remedies for treating asthma, bronchitis and emphysema. Theophylline found in medicine is made from extracts from coffee or tea. Theobromine is weaker than caffeine and theophylline – has one tenth of the stimulating effect. When isolated in pure form, caffeine is a white crystalline powder that tastes very bitter. Recreationally, it is used to provide a ‘boost in energy’ or a feeling of heightened alterness. It’s often used to stay awake longer. Caffeine inhibits the action of an enzyme, phosphodiesterase, whose job it is to inactive a molecule called cyclic adenosine monophosphate (AMP). Cyclic -AMP is involved in the formation of glucose in the bloodstream. Deactivation of phosphodiesterase by caffeine frees cyclic – AMP to do its job, more glucose appears, and we feel more energetic. Caffeine is an addictive drug. Among its many actions it operates using the same mechanisms that amphetamines, cocaine and heroin use to stimulate the brain. Caffeine’s effects are milder but it is manipulating the same channels and that it is one of the things that give caffeine its addictive qualities. It is one of the most widely used drugs. More than 90% of the population Britain consume it everyday and its long-term effects are of current interest. Purines are usually synthesised by Traube’s method in which a 4, 5 – diaminopyrimidine is treated with formic acid or, better, sodium dithioformate.4, 5- diaminopyrimidines are themselves obtained from 4- aminopyrimidines by nitrosation followed by reduction or via diazonium coupling of activated methylene compounds followed by cyclisation and reduction. Two examples are as follows: Uric acid (an 8-Hydroxypurine) are made using ethyl chloroformate in place of formic acid: Uric acid is then the starting material for other purines: Summary The term alkaloid refers to any Nitrogen containing compound extracted from plants, although the word is used loosely and some compounds of non-plant origin are also commonly known as alkaloids. The name is derived from their characteristic basic properties (alkali-like), which are induced by the lone-pair of electrons on nitrogen. The basic nature of the alkaloids, in conjunction with their particular three-dimensional architecture, gives rise to often-potent physiological activities, e.g. the narcotics morphine and heroin. The laboratory synthesis of an alkaloid can be a challenging problem. The goal nowadays is not only to synthesise the natural product, but also to do so from simple molecules by a short elegant pathway. Such syntheses have practical importance because many alkaloids are desirable drugs. Large amounts of these alkaloids are often difficult to obtain from natural sources. A simple synthesis can provide an alternative supply of such a drug. The 19th century was the heyday for structural studies on the alkaloids and the 20th century was notable for the large number of elegant syntheses that have been accomplished. Virtually all of the major alkaloids have now been synthesised.

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