Katalin Nogradi

Synthesis of vinca alkaloids and related compounds—XVII: Chiral synthesis of vinca alkaloids from l-Tryptophan

Abstract Starting from l -tryptophan two chiral syntheses of the 3S, 17S-lactam 11, an intermediate for the preparation of (+)-vincamine and its derivatives, were elaborated in good overall yield and with an optical purity of 96%.

A 13C and 1H nuclear magnetic resonance study of some diastereoisomeric homoeburnane derivatives

Several 14-hydroxy-E-homoeburnane diastereoisomers have been synthesized and studied by 1H and 13C n.m r spectroscopy. The relative configurations and predominating conformations have been established. It has been shown that previous assignments of C-17 and C-20 signals of trans-D/E-ring-fused Vinca alkaloids must be reversed.

The influence of 5-HT(2A) activity on a 5-HT(2C) specific in vivo assay used for early identification of multiple acting SERT and 5-HT(2C) receptor ligands.

As a result of our exploratory programme aimed at elaborating dually acting compounds towards the serotonin (5-HT) transporter (SERT) and the 5-HT2C receptor a novel series of 3-amino-1-phenylpropoxy substituted diphenylureas was identified. From that collection two promising compounds (2 and 3) exhibiting highest 5-HT2C receptor affinity strongly inhibited the 5-HT2C receptor agonist 1-(3-chlorophenyl)piperazine (mCPP) induced hypomotility in mice. In further pursuance of that objective (2-aminoethyl)(benzyl)sulfamoyl diphenylureas and diphenylpiperazines have also been elaborated. Herein we report the synthesis of potent multiple-acting compounds from this new class. However, when two optimized representatives (6 and 14) possessing the desired in vitro profile were tested neither reduced the motor activity of mCPP treated animals. Comparative albeit limited in vitro structure-activity relationship (SAR) analysis and detailed in vivo studies are discussed and explanation for their intricate behaviour is proposed.