Synthetic studies towards D-modified paclitaxel analogues
Sintetičke studije analoga paklitaksela sa modifikovanim D-prstenom
Abstract
A synthetic sequence has been developed for the preparation of 9,10- di-O-diacetyl-4-desmethylene-4β-(3-butenyl)-4α-hydroxy-5-O-mesyltaxicin I- -1,2-carbonate 3, an intermediate in an attempted synthesis of a cyclobutane paclitaxel analogue. A series of reactions of 3 were investigated, including the protection of the sterically hindered C-4α-hydroxy group and the oxidative cleavage of the terminal double bond. Cyclization of 13 to the cyclobutane-containing intermediate failed due to the unexpected instability of the dimethylsilane protecting group under basic conditions.
Razvijena je sintetička sekvenca za dobijanje 9,10-di-O-acetil-4-desmetilen-4β-(3-butenil)-4α-hidroksi-5-O-meziltaksicin I-1,2-karbonata (3), intermedijera u pokušanoj sintezi ciklobutanskog analoga paklitaksela. Ispitivana je mogućnost dalje hemijske transformacije jedinjenja 3, kao što je zaštita sterno izrazito zaštićene C-4α hidroksilne grupe i oksidativna fragmentacija terminalne dvostruke veze. Ciklizacija jedinjenja 13 nije dala željeni rezultat - intermedijer sa ciklobutanovim prstenom, što je posledica neočekivane nestabilnosti DMS-zaštitne grupe u baznim reakcionim uslovima.
Keywords:
taxoids / taxanes antitumor agents / radical allylation / silyl protecting groupsSource:
Journal of the Serbian Chemical Society, 2012, 77, 11, 1529-1539Publisher:
- Serbian Chemical Soc, Belgrade
Projects:
DOI: 10.2298/JSC120626094F
ISSN: 0352-5139