R-102557
Chemical Name: (2R,3R)-2-(2,4-Difluorophenyl)-3-[trans-2-[4-[4-(2,2,3,3-tetrafluoropropoxy)phenyl]buta-1(E),3(E)-dienyl]-1,3-dioxan-5-ylsulfanyl]-1-(1,2,4-triazol-1-yl)-2-butanol
CAS No. 183800-35-3
项目整合开发状态: Preclinical
项目研究机构: Sankyo (Originator)
合成路线:4-Hydroxybenzaldehyde (I) was alkylated with 2,2,3,3-tetrafluoropropyl tosylate (A) to give ether (II).Subsequent Horner-Emmons condensation of (II) with triethyl phosphonocrotonate (III) provided dienoate (IV),that was further reduced to alcohol (V) by means of DIBAL.Oxidation of (V) with activated MnO2 then gave aldehyde (VI).
合成路线:Displacement of tosylate (VII) with sodium thioacetate afforded thioester (VIII) (1).Hydrolysis of the thioester (VIII) in the presence of NaOMe,followed by condensation of the intermediate thiol with the chiral epoxide (IX) furnished the mercapto alcohol (X).Hydrolysis of the cyclic acetal of (X) in methanolic HCl gave triol (XI).This was finally condensed with aldehyde (VI) in the presence of p-TsOH and molecular sieves to yield the title compound.
合成路线:Addition of the thiol liberated from thioester (VII) in the presence of NaOMe to the chiral epoxide (VIII) afforded thioether (IX).Acid hydrolysis of the acetal function of (IX) yielded diol (X).Then,acetalization of diol (IX) with aldehyde (XI) furnished the title compound.
📌 参考资料/链接：
参考文献标题:Triazole antifungal agent
文献作者:Oida,S.; Tanaka,T.; Tajima,Y.; Konosu,T.; Somada,A.; Miyaoka,T.; Yasuda,H.(Sankyo Co.,Ltd.)
参考来源:EP 0841327; JP 1996333350; US 5977152; WO 9631491
📄 详细内容
合成路线:Displacement of tosylate (VII) with sodium thioacetate afforded thioester (VIII) (1).Hydrolysis of the thioester (VIII) in the presence of NaOMe,followed by condensation of the intermediate thiol with the chiral epoxide (IX) furnished the mercapto alcohol (X).Hydrolysis of the cyclic acetal of (X) in methanolic HCl gave triol (XI).This was finally condensed with aldehyde (VI) in the presence of p-TsOH and molecular sieves to yield the title compound.
参考文献标题:Synthesis and antifungal activity of R-102557,a novel dioxane-triazole compound
文献作者:Oida,S.; et al.
参考来源:19th Symp Med Chem (Nov 17 1999,Tokyo) 1999,Abst 2P-15
合成路线:4-Hydroxybenzaldehyde (I) was alkylated with 2,2,3,3-tetrafluoropropyl tosylate (A) to give ether (II).Subsequent Horner-Emmons condensation of (II) with triethyl phosphonocrotonate (III) provided dienoate (IV),that was further reduced to alcohol (V) by means of DIBAL.Oxidation of (V) with activated MnO2 then gave aldehyde (VI).
合成路线:Displacement of tosylate (VII) with sodium thioacetate afforded thioester (VIII) (1).Hydrolysis of the thioester (VIII) in the presence of NaOMe,followed by condensation of the intermediate thiol with the chiral epoxide (IX) furnished the mercapto alcohol (X).Hydrolysis of the cyclic acetal of (X) in methanolic HCl gave triol (XI).This was finally condensed with aldehyde (VI) in the presence of p-TsOH and molecular sieves to yield the title compound.
合成路线:Addition of the thiol liberated from thioester (VII) in the presence of NaOMe to the chiral epoxide (VIII) afforded thioether (IX).Acid hydrolysis of the acetal function of (IX) yielded diol (X).Then,acetalization of diol (IX) with aldehyde (XI) furnished the title compound.
参考文献标题:Synthesis and antifungal activities of R-102557 and related dioxane-triazole derivatives
文献作者:Oida,S.; Tajima,Y.; Konosu,T.; nakamura,Y.; Somada,A.; Tanaka,T.; Habuki,S.; Harasaki,T.; Kamai,Y.; Fukuoka,T.; Ohya,S.; Yasuda,H.
参考来源:Chem Pharm Bull 2000,48(5),694