- 【來源】ICN Biomedical Research Products; Sigma Chemical Company; Toronto Research Chemicals, Inc.
- 〖目標產物〗Sinefungin, Compound-57926, A-9145, Antibiotic 32232RP
- 〖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).
- 〖參考〗Ghosh, A.K.; Liu, W.M.; Total synthesis of (+)-sinefungin. J Org Chem 1996, 61, 18, 6175
- 〖合成方法〗The oxidation of 1-O-mehyl 2,3-isopropylidene-D-ribofuranoside (I) gives the corresponding aldehyde (II), which is condensed with methyltriphenylphosphonium bromide by means of butyllithium in THF yielding methyl 5-deoxy-2,3-isopropylidene-5-methylene-D-ribofuranoside (III). Elimination of the isopropylidene protecting group by passing through an Amberlyst resin (acid form) affords the free ribofuranoside (IV), which is benzoylated with benzoyl chloride and triethylamine in dichloromethane to afford the dibenzoyl derivative (V). The methyl ribofuranoside (V) was converted into the 1-O-acetyl derivative (VI) and condensed with 2,6-dichloro-9H-purine (VII) by heating at 150 C to provide the dichloropurine derivative (VIII), which is treated with O-methylhydroxylamine and triethylamine to afford 2',3'-di-O-benzoyl-2-chloro-5'-deoxy-N-methoxy-5'-methyleneadenosine (IX). Finally, this compound is debenzoylated with ammonia in methanol.
- 〖參考〗Lau, J.; Knutsen, L.J.S. (Novo Nordisk A/S); Chemical cpds., their preparation and use. EP 0719275; JP 1999511436; US 5589467; WO 9507921
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