KFC-431

Chemical Name: 5(R)-[2(S)-Amino-3-(9-phenanthryl)propionamido]-1,5-dideoxy-1-(uracil-1-yl)-beta-D-allofuranuronic acid
项目整合开发状态: Biological Testing
项目研究机构: Kyorin (Originator)
合成路线: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.