Citrinin, (3R,4S)-( -)-I 2,3-Dimethyloxirane, trans-(-)-and cis-I Synthesis of erythro-and threo-3-arylbutan-
2-01s
The fungal metabolite (-)-citrinin (1) was synthesized for the first time. Reaction of the Grignard reagent of 2,4-bis(benzyloxy)-6-bromotoluene (3) with (2S)-trans-(-)-2,3-dimethyloxirane (6) in the presence of 1,5-cyclooctadienecopper(I) chloride as catalyst leads to the formation of (2S,3S)-(-)-7 with erythro configuration. Compound (-)-7 could be transformed into (2R,3S)-(-)-9 with threo configuration via the formate (1R,2S)-(+)-8 by a Mitsunobu reaction. Reaction of the Grignard reagent of 3 with the achiral cis-2,3-dimethyloxirane yielded directly (f)-9. The starting material 3 was readily available from 1,3-bis(benzyloxy)-5-bromobenzene (4). Formylation of 4 furnished the aldehyde 5 which could be reduced to 3 with borane. Hydrogenolysis of the benzyl ether groups in (-)-9 gave (-)-2 with threo configuration. The remaining steps to produce citrinin [(-)-11 from (-)-2 required carboxylation to 11, formylation and in situ ring closure with ethyl orthoformate to produce the required quinomethide structure. Application of the same reactions to (+)-9 and (f)-2 afforded (f)-citrinin in 40 % overall yield.