-药物合成数据库

【药物名称】

化学结构式(Chemical Structure):

参考文献No.	21574
标题:	Avermectin difluoro derivs.
作者:	Meinke, P.T.; Mrozik, H.; Fisher, M.H. (Merck & Co., Inc.)
来源:	EP 0638078; JP 1995506361; US 5229416; WO 9322307

合成路线图解说明: Protection of the 5- and 4''-secondary alcohols of avermectin B2a (I) with tert-butyldimethylsilyl chloride (TBDMS-Cl) and Et3N in DMF-CH2Cl2 gave the bis(silylether) (II). Subsequent Swern oxidation of the C-23 hydroxyl group with DMSO and oxalyl chloride at -78 C furnished ketone (III).

合成路线图解说明: The tertiary alcohol at position 7 of (III) was protected as the trimethylsilyl ether (V) with N,O-bis(trimethylsilyl)trifluoroacetamide (IV) in DMF (1). Then, the ketone carbonyl group was converted into the gem-difluoride (VI) by treatment with diethylaminosulfur trifluoride, and the silyl protecting groups of (VI) were finally removed using a solution of HF in pyridine-THF.

参考文献No.	483534
标题:	Synthesis of gem-difluoro-avermectin derivatives: Potent anthelmintic and anticonvulsant agents
作者:	Meinke, P.T.; Shoop, W.L.; Michae, B.F.; Blizzard, T.A.; Dawson, G.R.; Fisher, M.H.; Mrozik, H.
来源:	Bioorg Med Chem Lett 1998,8(24),3643

合成路线图解说明: Protection of the 5- and 4''-secondary alcohols of avermectin B2a (I) with tert-butyldimethylsilyl chloride (TBDMS-Cl) and Et3N in DMF-CH2Cl2 gave the bis(silylether) (II). Subsequent Swern oxidation of the C-23 hydroxyl group with DMSO and oxalyl chloride at -78 C furnished ketone (III).

合成路线图解说明: The tertiary alcohol at position 7 of (III) was protected as the trimethylsilyl ether (V) with N,O-bis(trimethylsilyl)trifluoroacetamide (IV) in DMF (1). Then, the ketone carbonyl group was converted into the gem-difluoride (VI) by treatment with diethylaminosulfur trifluoride, and the silyl protecting groups of (VI) were finally removed using a solution of HF in pyridine-THF.