【药物名称】KFC-431
化学结构式(Chemical Structure):
参考文献No.585847
标题:Novel nikkomycin analogues: Inhibitors of the fungal cell wall biosynthesis enzyme chitin synthase
作者:Obi, K.; Uda, J.-I.; Iwase, K.; Sugimoto, O.; Ebisu, H.; Matsuda, A.
来源:Bioorg Med Chem Lett 2000,10(13),1451
合成路线图解说明:

Protection of D-ribose (I) by refluxing in MeOH, HCl and acetone affords derivative (II), which is oxidized under Collins conditions with CrO3 and pyridine in dichloromethane to provide aldehyde (III). Condensation of (III) with (phenylsulfanyl)nitromethane (IV) in tert-BuOH/THF in the presence of tert-BuOK, followed by treatment with MsCl and DIEA, furnishes nitro alkene (V), which is first treated with potassium trimethylsilanoate (KOTMS) in DMF/MeOH and then ozonolyzed (with hydrolytic work-up with methanolic citric acid) to give thioester (VI). Triflation of alpha-hydroxy thioester (VI) with triflic anhydride (Tf2O) in dichloromethane in the presence of pyridine, followed by hydrolysis with mercurium acetate (Hg(OAc)2) in MeOH, yields methyl ester (VII). Treatment of triflate (VII) with NaI and NaN3 in DMF affords azide (VIII), which is converted into triacetate (IX) by first deisopropylation by treatment with Dowex 50 W H+ in MeOH, acetylation with acetic anhydride (Ac2O) in pyridine and acetolysis with HOAc/Ac2O with catalysis by H2SO4 in dichloromethane. Condensation of triacetate (IX) with uracil derivative (X) by means of TMSOTf in acetonitrile provides beta-nucleoside (XI), which is hydrogenated over Pd/BaSO4 in acidic methanol and then hydrolyzed with Ba(OH)2 in dioxane to furnish uracil polyoxin C (XII). Coupling of (XII) with Boc-protected amino acid (XIII) by means of N-hydroxysuccinimide (HOSu)/DCC furnishes derivative (XIV), which is then converted into the final compound by Boc removal with TFA.

参考文献No.628617
标题:(Phenylthio)nitromethane in the total synthesis of polyoxin C
作者:Lebold, S.A.; Barrett, A.G.M.
来源:J Org Chem 1990,55(12),3853
合成路线图解说明:

Protection of D-ribose (I) by refluxing in MeOH, HCl and acetone affords derivative (II), which is oxidized under Collins conditions with CrO3 and pyridine in dichloromethane to provide aldehyde (III). Condensation of (III) with (phenylsulfanyl)nitromethane (IV) in tert-BuOH/THF in the presence of tert-BuOK, followed by treatment with MsCl and DIEA, furnishes nitro alkene (V), which is first treated with potassium trimethylsilanoate (KOTMS) in DMF/MeOH and then ozonolyzed (with hydrolytic work-up with methanolic citric acid) to give thioester (VI). Triflation of alpha-hydroxy thioester (VI) with triflic anhydride (Tf2O) in dichloromethane in the presence of pyridine, followed by hydrolysis with mercurium acetate (Hg(OAc)2) in MeOH, yields methyl ester (VII). Treatment of triflate (VII) with NaI and NaN3 in DMF affords azide (VIII), which is converted into triacetate (IX) by first deisopropylation by treatment with Dowex 50 W H+ in MeOH, acetylation with acetic anhydride (Ac2O) in pyridine and acetolysis with HOAc/Ac2O with catalysis by H2SO4 in dichloromethane. Condensation of triacetate (IX) with uracil derivative (X) by means of TMSOTf in acetonitrile provides beta-nucleoside (XI), which is hydrogenated over Pd/BaSO4 in acidic methanol and then hydrolyzed with Ba(OH)2 in dioxane to furnish uracil polyoxin C (XII). Coupling of (XII) with Boc-protected amino acid (XIII) by means of N-hydroxysuccinimide (HOSu)/DCC furnishes derivative (XIV), which is then converted into the final compound by Boc removal with TFA.

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