First total synthesis of 5(S)-hydroxyrecifeiolide

Abstract

The first total synthesis of recently isolated 5(S)-hydroxyrecifeiolide has been described in ten straight forward linear steps with 14% of overall yield. The key reaction involves Jacobsen’s hydrolytic kinetic resolution, Copper catalysed Grignard reaction, Steglich esterification and ring closing metathesis reaction using Grubb's 2nd generation catalyst making the synthesis very elegant and simple. The stereogenic center at C5 was generated via Jacobsen's HKR which was confirmed by the Mandelate ester strategy as well as HPLC purity.

Graphical Abstract

Keywords:

• Antifungal
• Jacobsen’s HKR
• macrolide
• ring closing metathesis
• Steglich esterification

Notes

1 See SI for table of spectroscopic data for natural and synthetic 5(S)-hydroxyrecifeiolide.

Additional information

Funding

KKB thanks for CSIR, New Delhi for financial assistance in the form of fellowship. Authors thanks the Director of CSIR-IICT for the support [IICT/Pubs./2019/318].