BMS-200532, MC-134-248

Chemical Name: 3(S)-Benzamido-2(R)-hydroxybenzenepropionic acid (2aR,4S,4aS,6R,9S,11S, 12S,12aR,12bS)-6-acetoxy-12b-(cyclopropylcarbonyloxy)-12-(2,4-difluorobenzoyloxy)-4,11-dihydroxy-4a,8,13,13- tetramethyl-5-oxo-2a,3,4,4a,5,6,9,10,11,12,12a,12b-dodecahydro-1H-7,11- methanocyclodeca[3,4]benz[1,2-b]oxet-9-yl ester
CAS No. 230972-99-3
项目整合开发状态: Biological Testing
项目研究机构: Bristol-Myers Squibb (Originator), Virginia Tech (Originator)
合成路线:Paclitaxel (I) was sequentially protected at the 2'-O with tert-butyldimethylsilyl chloride and imidazole and then at the 7-O with triethylsilyl chloride to afford the bis-silyl derivative (II).Selective hydrolysis of the benzoate ester group of (II) using Triton B provided (III).The vicinal 1,2-diol group of (III) was protected as the cyclic carbonate (IV) by treatment with either triphosgene or carbonyldiimidazole.The remaining free hydroxyl group of (IV) at position 4 was then acylated with cyclopropanecarbonyl chloride (V) in the presence of lithium hexamethyldisilazide to furnish the corresponding ester (VI).Subsequent deprotection of the cyclic carbonate ester of (VI) was achieved by selective hydrolysis with LiOH to afford diol (VII).Regioselective acylation of (VII) on the 2-hydroxyl with 2,4-difluorobenzoic acid (VIII) and DCC produced ester (IX).The final desilylation step was performed by treatment with HF-pyridine.