Biomimetic synthesis of acid-sensitive (−)- and (+)-caparrapi oxides, (−)- and (+)-8-epicaparrapi oxides, and (+)-dysifragin induced by artificial cyclases

Asymmetric total syntheses of acid-sensitive (−)- and (+)-caparrapi oxides (1) and (+)-8-epicaparrapi oxide (2) from farnesol (10) are achieved using Sharpless–Katsuki epoxidation and Lewis acid-assisted chiral Brønsted acid (chiral LBA)-induced polyene cyclization as key steps. The relative configuration of (+)-dysifragin (4) is determined by a single-crystal X-ray diffraction and its total synthesis is accomplished by the diastereoselective epoxidation of (+)-1. Furthermore, (−)-1 can be directly synthesized from (S)-nerolidol (3) and (R)-LBA with 88% ds by reagent control, which overcame substrate control, while (−)-2 is obtained from (R)-3 and (R)-LBA with >99% ds by the double asymmetric induction.

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