- 【化学名】[(3aS,8aR)-2-Oxo-8,8a-dihydro-2H-indeno[1,2-d][1,3]oxazol-3(3aH)-yl]lithium
- 【CAS登记号】
- 【结构式】
- 【分子式】C10H8LiNO2
- 【分子量】181.1198
- 【来源】
- 【合成情况】
- 〖目标产物〗Sinefungin, Compound-57926, A-9145, Antibiotic 32232RP
- 〖合成路线〗
- 〖合成方法〗A total synthesis of (+)-sinefungin has been reported: The reaction of D-ribose (I) with acetone and methanol by means of CuSO4 and a catalytic amount of H2SO4 gives methyl 2,3-O-isopropylidene-beta-D-ribofuranoside (II), which is oxidized to the aldehyde (III) with oxalyl chloride in DMSO/dichloromethane. The Wittig condensation of (III) with triethyl phosphonoacetate (IV) by means of NaH in THF affords the unsaturated ester (V), which is hydrogenated with H2 over Pd/C in ethyl acetate and saponified with LiOH in methanol/water to give the propionic acid (VI). The condensation of (VI) with the chiral oxazolidone (VII) by means of pivaloyl chloride and triethylamine in THF yields the oxalidone (VIII). The stereoselective alkylation of (VIII) with allyl bromide by means of lithium hexamethyldisylazide in THF affords the 2(S)-allyl derivative (IX), which is hydrolyzed with LiOH in THF/water to the corresponding free acid (X). The Curtius degradation of the acid (X) by means of diphenyl phosphorazidate and benzyl alcohol gives the corresponding benzyloxycarbonylamino derivative (XI), which is benzylated with benzyl bromide to the fully protected compound (XII). The ozonolysis of the allyl double bond of (XII) with O3 in methanol/dichloromethane yields the aldehyde (XIII).
- 〖参考〗Ghosh, A.K.; Liu, W.M.; Total synthesis of (+)-sinefungin. J Org Chem 1996, 61, 18, 6175
新药研发行业门户网站
制药行业专业信息平台
