Solution- and soluble-polymer supported asymmetric syntheses of six-membered ring prostanoids.
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 1H-NMR analysis of the intermediates in the synthesis, and provided an avenue for the construction of six-membered ring prostanoid libraries.
López-Pelegrín
J A
JA
Department of Chemistry and The Skaggs Institute for Chemical Biology, La Jolla, CA 92037, USA.
Janda
K D
KD
D011108:Polymers; D011453:Prostaglandins / Q000138:chemical synthesis* / Q000737:chemistry; D012996:Solutions; D013057:Spectrum Analysis
D011108:Polymers; D011453:Prostaglandins; D012996:Solutions