Solution- and Soluble-Polymer Supported Asymmetric Syntheses of Six-Membered Ring Prostanoids
作者:José A. López-Pelegrín、Kim D. Janda
DOI:10.1002/1521-3765(20000602)6:11<1917::aid-chem1917>3.0.co;2-7
日期:2000.6.2
An asymmetric synthesis of prostanoids containing a six-membered ring core structure (11a-homoprostaglandins), both in solution and using non-cross-linked polystyrene (NCPS) as a soluble support, was developed. Target molecule 1 was generated in a convergent fashion using a three-component coupling strategy, wherein chiral enone (R)-2 was the precursor of the central ring and the cuprate 3 and triflate 4 were used to introduce the side chains. The chiral center of (R)-2 directed the facial selectivity of the conjugate addition reaction which then dictated the stereochemical outcome of the subsequent alpha alkylation. Attachment of a six-membered ring scaffold to NCPS facilitated purification without compromising synthetic yields, still allowed H-1-NMR analysis of the intermediates in the synthesis, and provided an avenue for the construction of six-membered ring prostanoid libraries.