The fungal metabolite (R)‐(+)‐pulvilloric acid [(+)‐1] was synthesized for the first time. Reaction of the Grignard reagent of 5 with 2‐pentyloxirane (S)‐(−)‐4 in the presence of 1,5‐cyclooctadienecopper(I) chloride as the catalyst led to (S)‐(+)‐6. The enantiomer (S)‐(−)‐4 was prepared from dimethyl L‐malate via the dioxolane (S)‐(+)‐3. The alcohol (S)‐(+)‐6 was transformed into (R)‐(−)‐6 via the benzoate (R)‐(−)‐7 by a Mitsunobu reaction. Hydrogenolysis of (−)‐6 gave the resorcyl alcohol (R)‐(+)‐2. The remaining steps to produce (R)‐(+)‐1 from (+)‐2 required carboxylation to (R)‐(−)‐8, formylation and in situ ring closure with triethyl orthoformate to furnish the required quinomethide structure. Application of the same reactions to (S)‐(+)‐6 afforded (S)‐(−)‐1 via the intermediates (S)‐(−)‐2 and (S)‐(+)‐8. With (±)‐6 as starting material (±)‐2, (±)‐8 and (±)‐1 were prepared.
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‐dimethyl‐oxirane yielded directly (±)‐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 [(−)‐1] 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 (±)‐2 afforded (±)‐citrinin in 40% overall yield.
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