An efficient stereoselective total synthesis of 11β-methoxycurvularin

Abstract

A very short and efficient stereoselective total synthesis of a macrocyclic ketone, 11β-methoxycurvularin was achieved by employing the Sharpless asymmetric epoxidation, formation of propargyl alcohols from an epoxy-chloride, and intramolecular Friedel-Crafts acylation as the key steps.

Total synthesis of two potent anti-inflammatory macrolactones of the oxacyclododecindione type

“…Remarkably, a similar approach only resulted in low yields when applied to the preparation of the less substituted saturated macrolactone (S)-curvularin [4][5][6][7][8][9][10] or 11-methoxycurvularin. 11,12 While the elucidation of the relative configuration at C14 and C15 was uncertain, 1 the (S)-configuration was tentatively assigned to Ring-opening of commercial cis-2,3-epoxybutane (10) with an allyl cuprate yielded 3-methylhex-5-en-2-ol (11a), 13 which was then protected as the PMB-ether 14 (Scheme 2). Subsequent hydroboration with 9-borabicyclo[3.3.1]nonane (9-BBN) and oxidative work-up afforded alcohol 13a.…”

A Unified Synthetic Approach to Optically Pure Curvularin-Type Metabolites

“…To further explore their pharmaceutical activities, a number of strategies were disclosed to synthesize the curvularin-type metabolites using various reactions as the key steps, such as Friedel–Crafts acylation, Diels–Alder cycloaddition, aryne acyl alkylation, umpolung Pd-catalyzed α-arylation, etc. Among these strategies, ring-closing metathesis (RCM) approaches were advantageous in simple operations and easily available starting materials and could be applied to the synthesis of unsaturated curvularin-type metabolites, such as dehydrocurvularin ( 2 ).…”

“…The stereogenic center of 19 would finally be present in the final targets 10 and 11 and induce another stereogenic center to be generated . Enone 18 could be prepared by Friedel–Crafts acylation from the starting material 17 .…”