Stereoselective Total Synthesis of (±)-Peribysin E

Radical cyclization of iodoketone 3 afforded cis-hydrindanone 8. Compound 8 was converted into key intermediate 5 via conventional
transformations. Annulation of a spiro-lactal unit to 5 was pursued with three different approaches. In the first approach,
radical cyclization of propargyl ester 17 provided spiro-lactone 18 with an undesired stereochemistry. Attempts to invert the
stereochemistry at the spiro-center via retro-aldol and aldol condensation
of compound 20 failed. In the second approach, key intermediate 5 was transformed into 23. Acylation of compound 23 gave 24 as a single diastereomer with the
desired stereochemistry but in low yield. NBS bromination of 24 followed by lactone formation gave 26 in low
yield. Alternatively, allylic oxidation of 24 with SeO2 followed by lactonization gave 26 also in low
yield. Finally, a third approach employing a semipinacol-type rearrangement
of epoxy-alcohol 33 gave aldehyde 34 with
the desired stereochemistry. Treatment of compound 34 with HCl in MeOH effected spiro-lactal formation and provided (±)-peribysin
E. The overall yield of our synthesis is 3.2% from 2-methylcyclohenen-1-one.

碘酮3的激进环化反应得到顺式-水合二氢萘酮8。通过常规转化将化合物8转化为关键中间体5。尝试通过螺环萘单元与5的环合反应，采用三种不同的方法。在第一种方法中，丙炔酯17的激进环化反应提供了具有不期望立体化学的螺环内酯18。通过逆α-酮-β-烯醇缩合和α-酮缩合化合物20，试图翻转螺环中心的立体化学未能成功。在第二种方法中，将关键中间体5转化为23。化合物23的酰化反应得到单一构型异构体24，具有期望的立体化学，但产率较低。NBS溴化24随后形成内酯得到26，产率较低。或者，用SeO2对24进行烯丙基氧化，随后进行内酯化也得到26，产率同样较低。最后，采用半缩酮型重排环氧醇33的第三种方法，得到了具有期望立体化学的醛34。将化合物34与HCl在甲醇中处理，实现了螺环萘的形成，并提供了(±)-peribysin E。本合成方法的整体产率为从2-甲基环己烯-1-酮得到的3.2%。