[Total synthesis and properties of prostaglandins. XXI. Synthesis of a 4,4-dimethyl-4-sil analog of 11-deoxyprostaglandin E1]. / Total'nyi sintez i svoistva prostaglandinov. XXI. Sintez 4,4-dimetil-4-sila-analoga 11-dezoksiprostaglandina E1.

Total synthesis of a new prostaglandin analogue, 11-deoxy-4,4-dimethyl-4-sil-prostaglandin E1, is carried out through synthesis of a silicon-containing alpha-chain precursor and a 2-substituted cyclopentenone derivative followed by their cuprate-induced interaction.

[Cyclic analogs of des-Arg9-[Leu8]bradykinin]. / Tsiklicheskie analogi Dez-Arg9-[Leu8]bradykinina.

Four cyclic derivatives of des-Arg9[Leu8]bradykinin have been obtained by classical methods of peptide chemistry. They are cyclo-(-X-Arg-Pro-Pro-Gly-Phe-Gly-Pro-Leu-), where X=Lys or none, and cyclo-(Y-Arg-Pro-Pro-Gly-Phe-Ser-Pro-Leu-), where Y= Lys or Orn. Peptide bonds have been formed by the pentafluorophenylester method, and cyclization has been carried out in a diluted dioxane solution with 40% yield. Subsequent cleavage of protecting groups was made by treatment with hydrogen fluoride. The products obtained were purified by droplet counter-current chromatography. These substances liberate histamine from the rat mast cells comparably to bradykinin and fail to produce myotripic and vascular effects.

[Cyclic analogs of substance P. I. Cyclo(11----epsilon 5)-[Lys5] substance P-(5-11)]. / Tsiklicheskie analogi veshchestva P. I. Cyclo(11----epsilon 5)- [Lys5] veshchestvo P-(5-11).

Two solution syntheses of cyclo(11----5 epsilon)-[Lys5]substance P-(5-11) (CLP) were carried out. The first synthesis involved the stepwise elongation of the peptide chain starting from glycine tert-butyl ester. At the stage of hexapeptide deprotection, the cleavage of Boc and But groups was accompanied by tert-butylation of the Met residue. Cyclization was carried out via a pentafluorophenyl ester intermediate. The benzyloxycarbonyl-cyclopeptide (Z-CLP) formed was deprotected by catalytic transfer hydrogenation. A (3 + 4) block coupling strategy was used in course of the repeated preparation of the linear precursor of CLP. Optimization of the cyclization and subsequent deprotecting stages lead to increased yields and facilitated the synthetic procedure. Z-CLP was found to possess myotropic activity on isolated guinea pig ileum (alpha = 0.55 +/- 0.18; pD2 = 7.97 +/- 0.20), whereas CLP was inactive in these experiments. Z-CLP causes a slight two-phase effect on arterial pressure in rats, CLP being inactive. Similar to substance P, CLP displays an antidepressant-like effect in mice as indicated by the swimming test.