Structure and Stereochemistry of the a-Amino Acids

L. patella from Fiji contained patellins 1-5 (50-54) [82] and earlier, solution- and solid-state conformational studies were carried out on patellin 2 (51), and the structure was determined by X-ray analysis [83]. A Lissoclinum sp. from the Great Barrier Reef yielded patellins 3 (52), 5 (54) and 6 (55) and the heptapeptide trunkamide A (56) [82]. Compounds 50-56 were all identified by interpretation of spectral data and through use of Marfey s method to determine the absolute stereochemistry of the constituent amino acids [82]. A total synthesis of the proposed structure of trunkamide A (56) revealed that the structure... 

The diazabicycloheptane 14 obtained from cyclopentadiene and dibenzoyldiazene isomer-izes slowly to c/.s-bicyclic oxadiazine 15 when heated in a polar solvent48 50 or treated with an acid catalyst51. The structure and stereochemistry of the product 15 was confirmed by conversion to c/.v-2-amino- and c/.v-2-hydrazinocyclopentanol derivatives and comparison with authentic samples48,50. 

Some of the most interesting applications of organic structural theory to the elucidation of biosynthetic pathways were stimulated by efforts to formulate mechanisms for the biosynthesis of alkaloids. Conversely, consideration of implied biogenetic relations have occasionally helped structural determination. An important aspect of theories concerning alkaloid biosynthesis has been the assumed role of the aromatic amino acids in their formation. Only limited experimental evidence is available in this area. The incorporation of tyrosine- 8-C into morphine has been shown to be in accordance with a theory for its formation from 3,4-dihydroxyphenyl-alanine plus 3,4-dihydroxyphenylacetaldehyde. A stimulating theory of the biosynthesis of indole alkaloids, based on a condensation between trypt-amine and a rearrangement product of prephenic acid, has recently been published. The unique stereochemistry of C15 of these alkaloids had an important part in the formulation of the theory. Experimental proof of this theory would be valuable for several areas of alkaloid chemistry and biosynthesis. 

The dipole stereochemistry is sensitive to both structural change in the a-amino acids and aldehydes, and reaction temperature (87CC49). The reaction of 1,2,3,4-tetrahydroisoquinoline-l-carboxylic acid with benzaldehyde and Af-methylmaleimide gives a 1 1 mixture of the maleimide cycloadducts 244 and 245 of anti- and syn-dipoles 242 at 120°Cin DMF(1 hr), and a 2.7 1 mixture at 21°C in the same solvent (120 hr). Because MNDO calculations on the related anti- and syn-ylides 240 show that syn-240 is 1.8 kcal/mol more stable than anti-240, the preference of the anti-ylide cycloadducts 245 must be a kinetic result. 

A more complex member of the kainoid amino acid class of natural products is isodomoic acid G. This structure lacks the C4 stereocenter but instead possesses an exocycUc tetrasubstituted alkene. The core structure was constructed in a single step by nickel-catalyzed cycUzation of 10 with the vinylzirconium alkylating reagent 11 in 74% yield (Scheme 8.12) [34]. Notably, the pyrrolidine five-membered ring, C2/C3 relative stereochemistry, and 1,3-diene motif were assembled in a completely stereoselective fashion in a single operation. Sequential deprotection and oxidation steps afforded isodomoic acid G. 

Although Miller has shown that the passage of an electric discharge through mixtures of methane, ammonia and water vapour (possible constituents of a primeval atmosphere), results in the production of some a-amino acids, these always occur as racemic mixtures of the l and d forms. In biological systems, both structural and functional proteins are built almost exclusively from L-amino acids. It is clearly easier to construct a well-ordered macromolecule from residues having the same stereochemistry, but the original selection of one-handed residue over the other is as yet unexplained. 

Structural information chemical formula and stereochemistry in the case of a New Chemical Entity (NCE) or amino acid sequence and glycosylation sites in the case of a biotech product... 

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