Studies on the synthesis and biological evaluation of the metabolite of clausenamide CM₂ and its stereoisomers.

The synthesis and biological evaluation of 5-hydroxy clausenamide (CM₂), one of the major metabolites of clausenamide, and its stereoisomers have been carried out. The absolute configurations of (-)- and (+)-CM₂ were assigned as 3S,4S,5S,6S and 3R,4R,5R,6R respectively based on (1)H NMR spectroscopic investigation and their chemical correlation to (-)- and (+)-clausenamidone (3). Electrophysiological assay showed that compound (+)-CM₂ and its C₆ epimer (+)-8a had significant effects on synaptic transmission and thus induced the long-term potentiation of the dentate gyrus.

Synthesis of N-substituted Clausenamide analogues.

A practical synthesis of N-substituted Clausenamide analogues, including (-) and (+) CM1, Piracetam analogue 1 and Nefiracetam analogue 2, have been developed.

[Studies on the synthesis and antitumor activity of the derivatives of cephalotaxine alkaloid esters].

Aim: To design and synthesize some cephalotaxine and drupacine derivatives with different substituentes on C3'-N of taxol side chain.

Methods: Protective side chain acid VI (4'S,5'R) was prepared from optically active (2'R,3'S) methyl beta-phenyl glycidate I in five steps. The desired acids were coupled with cephlotaxine and drupacine respectively in the presence of 2-DPC/DMAP, followed by acidic hydrolysis and acylating to give novel alkloid esters with different substitutes on C3'-N.

[Synthesis and anti-inflammatory analgesic activities of sinomenine derivatives].

Aim: To provide basic data for the synthesis of new sinomenine derivatives.

Methods: The C ring in sinomenine was modified.

Results: Seven compounds were prepared and screened for anti-inflammatory and analgesic activities.

[Synthesis and antitumor activity of the derivatives of cephalotaxine and drupacine].

Aim: To make full use of cephalotaxus plant resources and search for antitumor agents with higher activities and lower side effects.

Methods: The C3 hydroxy groups of the cephlotaxine and drupacine were acylated by taxol side chain and its isomers to give a series of derivatives of cephlotaxine and drupacine.

Results: Six novel alkaloid esters were designed and synthesized.