Biomedical subjects

L F Szabó

Publications and source records attributed to L F Szabó.

4 recordsLinked to original sources

PubMed2001

Why are the terpenoid indole alkaloids of type I homochiral?

In the presence of the enzyme strictosidine synthase, the coupling reaction of secologanin and tryptamine is completely stereoselective and affords strictosidine with 3S configuration, exclusively. The stereoselectivity is transferred and retained in most indole alkaloids of type I in which C-3 is not involved in subsequent reactions. By using results of model reactions, the stereoselectivity was interpreted by the bulkiness of the enzyme temporarily attached to the N-4 atom in the formation of the indolenine intermediate. 3S configuration is kept in the subsequent 1,2-rearrangement into the beta-carboline structure. In the formation of the oxindole derivatives, the 3S configuration is preferred, but not necessarily complete.

Alkaloids↗

PubMed2001

Regio- and stereoselectivity in the coupling reaction of secologanin with dopamine derivatives.

The coupling reaction of tetraacetylsecologanin with dopamine and its N-benzyl derivative was investigated. In both series, stereoisomers at C-1, as well as regioisomer normal and neo compounds, were formed. Moreover, the N-unsubstituted products were partially lactamized, and the N-benzyl derivatives epimerized at C-1. In the products, the R configuration of C-1 over the S and the formation of the normal structure over the neo one predominated. The epimerization of both epimers gave an equilibrium of R and S in a ratio of 7:3 and was interpreted by cleavage of the C-1-N-2 bond. The fact that lactamization was much faster in the R than in the S series was explained on the basis of the supposed transition states. The structure, the configuration of C-1, and in several cases the conformations were established by detailed NMR studies and supported by chemical correlations.

Dopamine↗

PubMed2001

Investigation of the coupling reaction of tetraacetylsecologanin with oxotryptamine and its derivative.

The coupling reaction of tetraacetylsecologanin with 2,3-dihydro-2-oxotryptamine and its N(b)-benzyl derivative was investigated. With the benzylated amine, the reaction was stopped at the tetracyclic ester level, and with the unsubstituted amine it was immediately followed by lactamization. In both cases, the products were formed with high stereoselectivity at C-3, but as an epimeric pair of 7R and 7S in a ratio of 1:3. The bulky benzyl substituent at N-4 directed the stereoselectivity at C-3 in favor of the S configuration. In the nonbenzylated compounds, the reversible coupling reaction is probably nonstereoselective, but in lactamization the 3R epimer is sterically favored and faster and gives the final lactam in this configuration. The formation of the spiro compounds may serve as a model reaction in the interpretation of the stereoselectivity of the coupling reaction of secologanin with tryptamine in the presence of strictosidine synthase.

Alkaloids↗

PubMed2001

[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.

Alkaloids↗