新产品编号:54297
Chemical Name: (2'S,5'S,6S,6'R,7S,11R,13S,15S,17aR,20R,20aR,20bS)-7-[2,6-Dideoxy-4-O-(2,6-dideoxy-3-O-methyl-alpha-L-mannopyranosyl)-3-O-methyl-alpha-L-mannopyranosyloxy]-4',4'-difluoro-20,20b-dihydroxy-5',6,8,19-tetramethyl-6'-(1-methylpropyl)-3',4',5',6',6,7,10,11,14,15,17,17a,20a,20b-tetradecahydrospiro[11,15-methano-2H,13H,20H-furo[4,3,2-pq][2,6]benzodioxacyclooctadecino(13,2')-2H-pyran]-17-one
CAS No. 150896-00-7
项目整合开发状态: Preclinical
项目研究机构: Merck & Co. (Originator)
合成路线: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: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.
📌 参考资料/链接：
参考文献标题:Avermectin difluoro derivs.
文献作者:Meinke,P.T.; Mrozik,H.; Fisher,M.H.(Merck & Co.,Inc.)
参考来源:EP 0638078; JP 1995506361; US 5229416; WO 9322307
📄 详细内容
合成路线: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: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.
参考文献标题:Synthesis of gem-difluoro-avermectin derivatives: Potent anthelmintic and anticonvulsant agents
文献作者:Meinke,P.T.; Shoop,W.L.; Michae,B.F.; Blizzard,T.A.; Dawson,G.R.; Fisher,M.H.; Mrozik,H.
参考来源:Bioorg Med Chem Lett 1998,8(24),3643