Semisynthesis of D-ring modified taxoids: novel thia derivatives of docetaxel.
Two novel 5(20)-thia analogues of docetaxel have been synthesized from 10-deacetylbaccatin III or taxine B and isotaxine B. The key step of these syntheses is the concomitant thietane ring formation and acetylation of the tertiary alcohol at C-4. Both compounds are less cytotoxic than docetaxel but have divergent activity on microtubule disassembly.
Mercklé
L
L
Institut de Chimie des Substances Naturelles, CNRS 91198 Gif sur Yvette Cedex, France.
Dubois
J
J
Place
E
E
Thoret
S
S
Guéritte
F
F
Guénard
D
D
Poupat
C
C
Ahond
A
A
Potier
P
P
D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis* / Q000494:pharmacology; D000077143:Docetaxel; D006801:Humans; D007202:Indicators and Reagents; D007624:KB Cells; D008870:Microtubules / Q000187:drug effects; D017239:Paclitaxel / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology; D018515:Plant Leaves / Q000737:chemistry; D010946:Plants, Medicinal / Q000737:chemistry*; D043823:Taxoids
D000972:Antineoplastic Agents, Phytogenic; D007202:Indicators and Reagents; D043823:Taxoids; D000077143:Docetaxel; D017239:Paclitaxel