[Diversity and selectivity in biomolecules].
Nature provides molecular constructions in inexhaustible richness. She combines small building blocksacks, and from the great variety of the possible structures, the really existing molecules are selected by kinetic (actually enzymic) and thermodynamic control. The operation of this fundamental principle is demonstrated by means of the graph analysis, in the large community of the monoterpenoid indole alkaloids isolated from the species of the Apocynaceae, Loganiaceae and Rubiaceae plant families. Strictosidine, an alkaloid glucoside, is formed from a single enantiomer of secologanin and tryptamine by enzymic catalysis and with complete diastereoselectivity. It is the exclusive precursor of more than 2200 alkaloids. The configuration of one or more analogous centers of chirality of them is identical, i.e. homochiral, insofar it will be lost or changed in subsequent reactions. Strictosidine exists in a single, most stable conformer of the possible 324 ones. On simple secologanin derivatives it was proved, that the removal of the glucosyl unit by enzyme results, under kinetic control, in the formation of the epimer pair of the primary aglucone. However, proton catalysed hydrolysis gives, under thermodynamic control, the most stable epimer pair of the possible 48 aglucones formed in 368 elementary steps. In the deglucosylation of the strictosidine type compounds, in 2 series, 1 tricyclic, 8 tetracyclic and 16 pentacyclic aglucone types are formed by further oxa-, carba- and/or azacyclizations. The alkaloids derived from strictosidine can be grouped into one unrearranged (I) and two rearranged (II and III) skeletons, in normal and iso series as well as along a and b lines. The processes are directed partially by proton migrations. The really existing alkaloids are formed in subsequent chemical reactions. The rich molecular library obtained by that way reveals the fundamental unity of Nature in the material multiplicity, i.e. it lets shine up the beauty in the world of the biomolecules, too.
Semmelweis Egyetem, Szerves Vegytani Intézet, Hógyes Endre u. 7., Budapest, H-1092. szalasz@szerves.sote.hu
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D000470:Alkaloids / Q000737:chemistry / Q000627:therapeutic use; D004358:Drug Therapy / Q000379:methods; D006801:Humans; D004364:Pharmaceutical Preparations / Q000138:chemical synthesis / Q000737:chemistry*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000470:Alkaloids; D004364:Pharmaceutical Preparations