合成路线:6) Another route involves acetylation of the anhydro derivative (XVI) to give (XVII),which is converted to (XVIII) by treatment with sodium bromide in sulfuric acid and submitted to elimination with zinc and sodium hydroxide.
参考文献标题:Process for producing 1-(2,3-dideoxy-beta-D-glycero-pent-enofuranosyl)thymine
文献作者:Ikeda,T.; Asamura,K.(Yamasa Shoyu Co.,Ltd.)
参考来源:WO 9209599
合成路线:4) Reaction of thymine (IX) with 1-O-acetyl-2,3,5-tri-O-benzoylribose (X) and hexamethyldisilazane,trimethylsilyl chloride and trifluoromethanesulfonic acid in acetonitrile,followed by cleavage of the protecting groups with sodium methoxide in methanol gives 5-methyluridine (XI).Compound (XI) is converted to (XII) by means of 2-acetoxyisobutyryl bromide in acetonitrile,subsequent reaction of (XII) with zinc-copper in dimethylformamide yields (XIII),which is finally deprotected with sodium methoxide in methanol.5) 5-Methyluridine (XI) can also be converted to (XIV) by means of trimethylorthoacetate in acetic acid.Compound (XIV) is then treated with hydrobromic acid to give (XV),which is treated with zinc in acetonitrile and EDTA or is successively treated with acetic anhydride,zirconium oxide and tributylamine.
参考文献标题:Process for producing 2',3'-dideoxy-2',3'-didehydronucleoside
文献作者:Ebata,T.; Matsushita,H.; Mizutani,N.; Itoh,K.(Japan Tobacco Inc.)
参考来源:WO 9202516
合成路线:4) Reaction of thymine (IX) with 1-O-acetyl-2,3,5-tri-O-benzoylribose (X) and hexamethyldisilazane,trimethylsilyl chloride and trifluoromethanesulfonic acid in acetonitrile,followed by cleavage of the protecting groups with sodium methoxide in methanol gives 5-methyluridine (XI).Compound (XI) is converted to (XII) by means of 2-acetoxyisobutyryl bromide in acetonitrile,subsequent reaction of (XII) with zinc-copper in dimethylformamide yields (XIII),which is finally deprotected with sodium methoxide in methanol.5) 5-Methyluridine (XI) can also be converted to (XIV) by means of trimethylorthoacetate in acetic acid.Compound (XIV) is then treated with hydrobromic acid to give (XV),which is treated with zinc in acetonitrile and EDTA or is successively treated with acetic anhydride,zirconium oxide and tributylamine.
参考文献标题:Nucleoside derivs.and production thereof
文献作者:Shiragami,H.; Uchida,Y.; Izawa,K.(Ajinomoto Co.,Inc.)
参考来源:EP 0519464
合成路线:1) The first method ever reported involves the mesylation of thymidine (I) to give dimesylate (II),which is treated with sodium hydroxide in ethanol to yield oxetane (III).Finally,(III) is converted to stavudine by means of potassium tert-butoxide in DMSO.This process has been modified in order to obtain large quantities or to obtain [2-14C]-stavudine starting from [2-14C]-thymidine.2) A second closely related method,but using a different protecting group strategy,involves tritylation of the primary hydroxyl group of thymidine to give (IVa),which is then mesylated to give (Va).Elimination with TBAF/THF or t-BuOK/DMSO yields compound (VI),which is finally deprotected with acetic acid.3) A third synthesis starting from thymidine involves its protection with monomethoxytrityl chloride or picolyl chloride to give (IVb) or (IVc),respectively,which are mesylated to give (Vb) or (Vc).These are treated with phenyl diselenide and lithium aluminum hydride in tetrahydrofuran to yield compounds (VIIb) or (VIIc),which are treated with m-chloroperbenzoic acid in dichloromethane to afford (VIIIb) or (VIIIc).Finally,(VIIIb) is deprotected with methylamine in water and (VIIIc) is deprotected with acetic acid.
参考文献标题:Pharmaceutical compsn.comprising 3'-deoxythymidin-2'-ene (3'-deoxy-2',3'-didehydrothymidine) in treating patients infected with retrovirus
文献作者:Lin,T.-S.; Prusoff,W.H.(Yale University)
参考来源:EP 0273277
合成路线:1) The first method ever reported involves the mesylation of thymidine (I) to give dimesylate (II),which is treated with sodium hydroxide in ethanol to yield oxetane (III).Finally,(III) is converted to stavudine by means of potassium tert-butoxide in DMSO.This process has been modified in order to obtain large quantities or to obtain [2-14C]-stavudine starting from [2-14C]-thymidine.2) A second closely related method,but using a different protecting group strategy,involves tritylation of the primary hydroxyl group of thymidine to give (IVa),which is then mesylated to give (Va).Elimination with TBAF/THF or t-BuOK/DMSO yields compound (VI),which is finally deprotected with acetic acid.3) A third synthesis starting from thymidine involves its protection with monomethoxytrityl chloride or picolyl chloride to give (IVb) or (IVc),respectively,which are mesylated to give (Vb) or (Vc).These are treated with phenyl diselenide and lithium aluminum hydride in tetrahydrofuran to yield compounds (VIIb) or (VIIc),which are treated with m-chloroperbenzoic acid in dichloromethane to afford (VIIIb) or (VIIIc).Finally,(VIIIb) is deprotected with methylamine in water and (VIIIc) is deprotected with acetic acid.
参考文献标题: Production of 2',3'-dideoxy-2',3'-didehydronucleosides
文献作者:Starret,J.E.Jr.; Mansuri,M.M.; Martin,J.C.; Fuller,C.E.; Howell,H.G.(Bristol-Myers Squibb Co.)
参考来源:EP 0334368
合成路线:1) The first method ever reported involves the mesylation of thymidine (I) to give dimesylate (II),which is treated with sodium hydroxide in ethanol to yield oxetane (III).Finally,(III) is converted to stavudine by means of potassium tert-butoxide in DMSO.This process has been modified in order to obtain large quantities or to obtain [2-14C]-stavudine starting from [2-14C]-thymidine.2) A second closely related method,but using a different protecting group strategy,involves tritylation of the primary hydroxyl group of thymidine to give (IVa),which is then mesylated to give (Va).Elimination with TBAF/THF or t-BuOK/DMSO yields compound (VI),which is finally deprotected with acetic acid.3) A third synthesis starting from thymidine involves its protection with monomethoxytrityl chloride or picolyl chloride to give (IVb) or (IVc),respectively,which are mesylated to give (Vb) or (Vc).These are treated with phenyl diselenide and lithium aluminum hydride in tetrahydrofuran to yield compounds (VIIb) or (VIIc),which are treated with m-chloroperbenzoic acid in dichloromethane to afford (VIIIb) or (VIIIc).Finally,(VIIIb) is deprotected with methylamine in water and (VIIIc) is deprotected with acetic acid.
参考文献标题:1-(2,3-Dideoxy-beta-D-glycero-pent-2-enofuranosyl)thymine.A highly potent and selective anti-HIV agent
文献作者:Mansuri,M.M.; Starrett,J.E.Jr.; Ghazzouli,I.; Hitchcock,M.J.; Sterzycki,R.Z.; Brankovan,V.; Lin,T.S.; August,E.M.; Prusoff,W.H.; Sommadossi,J.P.; et al.
参考来源:J Med Chem 1989,32(2),461-6
产品链接: CAS No. 3056-17-5››