Total synthesis of prostaglandin-F2? through homoconjugate addition of an organocuprate reagent to a tricyclo[3.2.0.02,7]heptanone

Abstract

Prostaglandin-Fza has been synthesised from cyclopentadiene in a highly stereoselective ten-step sequence of reactions. The key step involves the coupling of a protected 3-hydroxyoct-1 -enyl unit to 3-dimethyl-t-butylsilyloxytricyclo [3.2.0.02*'] heptan-6-one through the use of a mixed organocuprate reagent.We are grateful to the S.R.C. and Allen and Hanburys Research for financial support (C.A.S.E. award to T. V. L.). Our thanks are due to Mr. John Paton for technical assistance.

Synthesis of the Potent Antiglaucoma Agent, Travoprost

“…We were attracted to a highly convergent approach to prostaglandin analogues involving addition of a cuprate reagent, incorporating the entire ω-side chain, to tricyclo[3.2.0.0 2,7 ]heptanone 5 developed by Roberts and Newton ).…”

Fluorination with ionic liquid EMIMF(HF)2.3 as mild HF source

“…Silyl ethers are readily cleaved by mild acidic hydrolysis [11] or by a fluoride ion generated by TBAF [12]. Hydrogen fluoride (4% solution of 95% HF aq.…”