新产品编号:84355
Chemical Name: (1R,9S,12S,13R,14S,17R,21S,23S,24R,25S,27R)-17-Ethyl-1,14-dihydroxy-23,25-dimethoxy-12-[2-[4(R)-[2(S)-hydroxy-2-(2-naphthyl)ethoxy]-3(R)-methoxycyclohex-1(R)-yl]-1(E)-methylvinyl]-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0(4,9)]octacos-18-ene-2,3,10,16-tetrone
CAS No. 160583-67-5 (non-specified steroch.)
项目整合开发状态: Preclinical
项目研究机构: Merck & Co. (Originator)
合成路线:Protection of ascomycin (I) by means of tert-butyldimethylsilyl trifluoromethanesulfonate in the presence of 2,6-lutidine provided the 14,4''-disilylated derivative (II).Selective removal of the 4''-silyl group of (II) with para-toluenesulfonic acid in MeOH-CH2Cl2 yielded the 14-protected compound (III).This was converted to allyl ether (V) upon treatment with allyl trichloroacetimidate (IV) and trifluoromethanesulfonic acid.Dihydroxylation of the allyl double bond of (V) with OsO4 and N-methylmorpholine-N-oxide,followed by oxidative cleavage of the resulting diol (VI) with sodium metaperiodate furnished aldehyde (VII).
合成路线:Addition of 2-naphthylmagnesium bromide (VIII) produced the corresponding carbinol as a diastereomeric mixture,from which the required isomer (IX) was isolated by preparative TLC.Finally,the silyl protecting group was cleaved by treatment with HF in pyridine.
📌 参考资料/链接：
参考文献标题:Potent immunosuppressive C32-O-arylethyl ether derivatives of ascomycin with reduced toxicity
文献作者:Armstrong,H.M.; Wong,F.; Holmes,M.A.; Sinclair,P.J.; Goulet,M.T.; Dumont,F.J.; Staruch,M.J.; Koprak,S.; Peterson,L.B.; Rosa,R.; Wilusz,M.B.; Wiederrecht,G.J.; Cryan,J.G.; Wyvratt,M.J.; Parsons,W.H.
参考来源:Bioorg Med Chem Lett 1999,9(14),2089-94
📄 详细内容
合成路线:The condensation of the 32-OH of ascomycin (I) with the diazoketone (II) by means of a Rh catalyst gives the addition product (III),which is silylated at the 24-OH with TES-Cl yielding the silyl ether (IV).The reduction of the new carbonyl group of (IV) with the chiral reducing agent (S)-OAB/BH3 and TEA affords the silylated target compound (V),which is finally treated with HCl to eliminate the TES- group.
参考文献标题:Rhodium-carbenoid-mediated intermolecular O-H insertion reactions: A dramatic additive effect.Application in the synthesis of an ascomycin derivative
文献作者:Nelson,T.D.; et al.
参考来源:Tetrahedron Lett 2000,41(12),1877
合成路线:Protection of ascomycin (I) by means of tert-butyldimethylsilyl trifluoromethanesulfonate in the presence of 2,6-lutidine provided the 14,4''-disilylated derivative (II).Selective removal of the 4''-silyl group of (II) with para-toluenesulfonic acid in MeOH-CH2Cl2 yielded the 14-protected compound (III).This was converted to allyl ether (V) upon treatment with allyl trichloroacetimidate (IV) and trifluoromethanesulfonic acid.Dihydroxylation of the allyl double bond of (V) with OsO4 and N-methylmorpholine-N-oxide,followed by oxidative cleavage of the resulting diol (VI) with sodium metaperiodate furnished aldehyde (VII).
合成路线:Addition of 2-naphthylmagnesium bromide (VIII) produced the corresponding carbinol as a diastereomeric mixture,from which the required isomer (IX) was isolated by preparative TLC.Finally,the silyl protecting group was cleaved by treatment with HF in pyridine.
参考文献标题:O-Heteroaryl,O-alkylheteroaryl,O-alkenylheteroaryl and O-alkynylheteroarylmacrolides having immunosuppressive activity
文献作者:Sinclair,P.J.; Goulet,J.; Wong,F.; Goulet,M.; Parsons,W.H.; Wyvratt,Matthew,J.
参考来源:US 5349061
合成路线:Protection of ascomycin (I) by means of tert-butyldimethylsilyl trifluoromethanesulfonate in the presence of 2,6-lutidine provided the 14,4''-disilylated derivative (II).Selective removal of the 4''-silyl group of (II) with para-toluenesulfonic acid in MeOH-CH2Cl2 yielded the 14-protected compound (III).This was converted to allyl ether (V) upon treatment with allyl trichloroacetimidate (IV) and trifluoromethanesulfonic acid.Dihydroxylation of the allyl double bond of (V) with OsO4 and N-methylmorpholine-N-oxide,followed by oxidative cleavage of the resulting diol (VI) with sodium metaperiodate furnished aldehyde (VII).
合成路线:Addition of 2-naphthylmagnesium bromide (VIII) produced the corresponding carbinol as a diastereomeric mixture,from which the required isomer (IX) was isolated by preparative TLC.Finally,the silyl protecting group was cleaved by treatment with HF in pyridine.
参考文献标题:O-Aryl,O-alkyl,O-alkenyl and O-alkynylmacrolides having immunosuppressive activity
文献作者:Sinclair,P.J.; Organ,H.M.; Wong,F.; Goulet,M.; Parsons,W.H.; Wyvratt,Matthew,J.
参考来源:US 5565560