[Stereochemistry of the reductive amination of 4-oxoproline derivatives with glycine esters]. / Stereokhimiia vosstanovitel'nogo aminirovaniia proizvodnykh 4-oksoprolina éfirami glitsina.

An amination of 4-oxoproline derivatives with glycine methyl or benzyl ester and sodium cyanoborohydride led to the mixtures of corresponding diastereomeric 4-cis- and 4-trans-glycinoproline derivatives. We found that the ratio of diastereomers mainly depends on the structure of 4-oxoproline ester groups and, to a lesser extent, on the structure of N-acyl substituents. The best results were achieved with tert-butyl ester group; it ensured good yields of the amination products and the greatest prevalence of 4-cis-isomers. The structure of ester group in glycine molecule only scarcely affected the resulting ratio of N-(N-benzyloxycarbonylglycyl)-4-glycinoprolines. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2002, vol. 28, no. 6; see also http://www.maik.ru.

[Hydrolysis of primary amide groups in Asn/Gln-containing peptides]. / Gidroliz pervichnykh amidnykh grupp v Asn/Gln-soderzhashchikh peptidakh]

Peptides Boc-Ala-Asn/Gln-OH and Boc-Asn/Gln-Ala-OH were saponified with barium hydroxide to corresponding Asp/Glu-containing peptides. Under the conditions of saponification, Boc-Asn-Ala-OH additionally afforded Boc-Asp-OH, isopeptide Boc-Asp(Ala)-OH, and Boc-NHSuc > Ala-OH, with the third being the key intermediate in these transformations. Boc-Asp(OMe)-Ala-OMe underwent similar transformations under treatment with diazomethane or triethylamine. Saponification with barium hydroxide was accompanied by a high epimerization of N-terminal amino acid residues, whereas the products of the diazomethane treatment of Boc-Asp(OMe)-Ala-OMe had a low degree of epimerization.

[Synthesis isomeric 4-prolylamines and 4,4'-diprolylamines]. / Sintez izomernykh 4-prolinilaminov i 4,4'-diprolinilaminov.

Starting from the previously described tert-butyl esters of 4-epimeric N-benzyloxycarbonyl-4-hydroxyprolines and N-benzyloxycarbonyl-4-trans- and 4-cis-trifluoroacetamidoproline tert-butyl esters, the corresponding un-protected 4-aminoprolines and a number of their partially protected derivatives were synthesized via the intermediate 4-O-mesyl and 4-azide derivatives. The reductive amination of N-benzyloxycarbonyl-4-oxoproline tert-butyl ester with ammonium acetate led to N-benzyloxycarbonyl-4-cis-4'-cis- and 4-cis-4'-trans-diprolinylamines. The 1H NMR and CD spectra of the synthesized compounds are described.

[Synthesis and biological activity of 7,8-dihydro derivatives of batrachotoxinin interacting with fast sodium channels]. / Poluchenie i issledovanie biologicheskoi aktivnosti 7,8-digidroproizvodnykh batrakhotoksinina, vzaimodeistvuiushchikh s bystrymi natrievymi kanalami.

7,8-Dihydrobatrachotoxinin (A) (I) was synthesized from 11 alpha-hydroxyprogesterone (III) by a 37-stage procedure. Trimethylpyrrolcarboxylate, benzoate as well as 2-azido-benzoate derivatives of (I) were obtained by mixed anhydride technique, the latter two derivatives being prepared also with tritium atoms in aromatic rings (sp. radioactivity about 28 Cu/mmol). Upon interaction with rat brain synaptosomes the apparent Kd of 7,8-dihydrobatrachotoxinin A 20 alpha-[4-3H]benzoate (Iv) was about 2,5 x 10(-6) M. The (Iv) specific binding was inhibited by aconitine with K0,5 = 1,3 x 10(4) M. Anemonia sulcata toxin II (ATX II) enhanced (Iv) affinity for the receptor up to 7 x 10(-7) M, the maximum binding capacity being 2,5 pmol/mg of protein. Benzocaine and tetracaine competitively displaced specifically bound toxin with K0,5 = 3,1 x 10(-4) M and 5,7 x 10(-7) M, respectively, in the presence of 10(-5) M ATX II. 2-Azido[5-3H]benzoate derivative (Id) was shown to be an effective probe for covalent labeling of the alkaloid toxin receptor of the sodium channel.