Amphetamine, structure synthesis

Fig. 1. A. Chemical structure of key molecules involved in the key steps in intracerebral synthesis and metabolism of dopamine. The successive steps are regulated by the enzymes tyrosine hydroxylase (TH), aromatic amino acid decarboxylase (AADC), monoamine oxidase (MAO) and dopamine-p-hydroxylase (DBH). B. Structure of key toxins and other drugs acting on dopamine neurones, including 6-hydroxydopamine (6-OHDA), a-methyl tyrosine, and amphetamine. For further details see Iversen and Iversen (1981) or Cooper et al. (1996).

METHYL-MA is a well studied drug, at least in animals. In both mice and rats, it is an exceptionally potent agent in creating the state of catatonia. Animal studies, prompted by the clandestine synthesis of METHYL-MA, have shown that there is indeed locomotor stimulation and some central effects, but these effects are somehow different than those of a simple amphetamine-like agent. The experimenter s conclusions, based on its structural resemblance to 4-MA and its proclivity to produce catatonia in some animal species and the ever-present possibility that there might be unsuspected neurochemical changes to be seen with its use, are that human experimentation should be discouraged. I have come to the same conclusion, but in my case this is based on a much more succinct observation I tried it and I didn t like it. 

This phase saw continuous advances in chemistry and medicine. Organic chemistry was now capable of the synthesis of relatively complex targets by multistep sequences. The concept of systematically preparing a compound series and testing it for a biological effect became common, as exemplified in Ehrlich s quest for antisyphilitic agents. More and more pure natural products were identified and their structures elucidated. Synthetic mimics became a reahty. For example, amphetamines were inspired by the natnral prodnct lead, ephedrine. 

Non-Phenethylamine Derivatives - The search for compounds which bear no structural relationship to phenethylamlnes and have anorectic properties continues. Current studies on Wy-5244 (XIV) show it to possess only weak sympathomimetic activity in isolated cat atria and rabbity aortic strips however the compound apparently does alter adrenergic receptor mechanisms since the actions of substances such as norepinephrine, d-amphetamine, phenoxybenzamine, and Imlpramine were profoundly influenced by Wy-5244.31 The synthesis of (XIV) and related compounds has been described.32... 

Indeed, PDC catalyzes mainly the reaction of pyruvate with benzaldehyde for the formation of (R)-PAC 27. This C—C bond formation, a two-carbon unit elongation, is coupled to the concomitant decarboxylation of pyruvate 26. This reaction is industrially developed for the synthesis of (—)-ephedrine by adding a second step, a reductive amination. Ephedrine (marketed by Merck especially) is a sympathomimetic amine commonly used as a stimulant, appetite suppressant, concentration aid, and decongestant, and it is used to treat hypotension associated with anesthesia. It is similar in structure to the (semisynthetic) derivatives amphetamine and meth-amphetamine. Chemically, it is an alkaloid derived from various plants in the genus Ephedra (family Ephedra-ceae). It works mainly by increasing the activity of noradrenaline on adrenergic receptors. ... 

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