Olivier Duclos

A highly efficient route to taxotere by the β-Lactam Synthon Method

Taxotere, a highly promising anticancer drug, is synthesized through an efficient coupling of 7,10-diTroc-10-deacetylbaccatin III with enantiomerically pure (3R,4S)-1-tBOC-3-EEO- 4-phenylazetidin-2-one which is obtained via chiral ester enolate - imine cyclocondensation.

SYNTHESIS AND BIOLOGICAL ACTIVITY OF 3'-ALKYL- AND 3'-ALKENYL-3'-DEPHENYLDOCETAXELS

Abstract 3-Alkyl- and 3′-alkenyl-3′-dephenyldocetaxels are synthesized from 10-deacetylbaccatin III based on the β-lactam synthon method in good yields. The cytotoxicity of the new taxoids are evaluated against different human tumor cell lines and their ability to inhibit the microtubules disassembly examined. The 3′-isobutenyl, 3′-crotyl, and 3′-isobutyl analogs possess very strong cytotoxicity as well as antitumor activity in vivo . 3′-Isobutenyl- as well as 3′-crotyl-3′-dephenyl-10-acetyldocetaxel shows ca. 20 times stronger activity against an adriamycin-resistant human breast cancer cell line (MCF7-R) than those o docetaxel and paclitaxel.

N-acyl-3-hydroxy-β-lactams as key intermediates for taxotere and its analogs

Abstract (3 R ,4 S )-3-(protected hydroxy)-4-substituted β-lactams bearing N -alkoxycarbonyl, N -arloxycarbonyl, and N -carbamoyl groups are found to be useful for the synthesis of taxotere and its analogs through coupling with baccatin III.

A versatile new synthesis of 4-aryl- and heteroaryl-[3,4-c]pyrrolocarbazoles by [4+2] cycloaddition followed by palladium catalysed cross coupling

Abstract 4-Bromo- and 4-trifluorosulfonyloxypyrrolo[3,4-c]carbazoles were prepared in five steps via a [4+2] cyclo-addition and were used as key intermediates in palladium-catalysed cross coupling reactions allowing the rapid generation of structurally diverse protein kinase C inhibitors.

Synthesis and SAR of 3- and 4-substituted quinolin-2-ones: discovery of mixed 5-HT1B/5-HT2A receptor antagonists

Quinolin-2-ones bearing a heteroaryl-piperazine linked by a two carbon chain at the 3- or 4-position were synthesised and evaluated as mixed 5-HT1B/5-HT2A receptor antagonists. Potent mixed antagonists were obtained with thieno[3,2-c]pyridine derivatives. In this series, compound 2.1 (SL 65.0472) proved to be functional antagonist at both the 5-HT2A receptor (rat in vivo 5-HT-induced hypertension model) and the 5-HT1B receptor (dog in vitro saphenous vein assay).