Stereoselective Synthesis of Microcarpalide

Abstract

The first total synthesis of the naturally occurring nonenolide, microcarpalide, is described. The key step in the synthesis was the ring-closing metathesis of a dienic ester prepared in turn by coupling an acid and an alcohol stereoselectively synthesized from (S,S)-tartaric acid and (R)-glycidol, respectively. [structure: see text]

Synthetic Studies of Natural 10-Membered Lactones, Mueggelone, Microcarpalide, and Sch 642305, Which Have Interesting Bioactivities

“…Connection of two fragments 35 and 37 was carried out under the Yamaguchi conditions, 14) and the resulting ester 38 was subjected to RCM using 1st-generation Grubbs catalyst. 26) High dilution conditions (1.4 mM) brought a result similar to Marco's group, 22,23) giving a 2:1 E/Z mixture of 10-membered lactone 39 in good yield. After purification of E-isomer, deprotection successfully afforded microcarpalide.…”

“…Finally, removal of the MEM group using TiCl 4 resulted in debenzylation to afford microcarpalide. Interestingly, compared with Marco's synthesis, 22) E/Z selectivity at the ring-closing step was greatly improved by changing the protective groups. Similarly, Ghosh et al also reported a total synthesis of microcarpalide using the same precursor 24 for RCM in 2005, 34) in which all four stereocenters were derived from D-mannitol (scheme not shown).…”

“…First synthesis of microcarpalide by Marco et al The first synthesis of microcarpalide was achieved by Marco and co-workers in 2002 (Scheme 2 [1]). 22,23) Their key reaction was the RCM 4) of ester 18 to form 10-membered lactone, and four stereocenters were derived from commercially available chiral pools. (R)-Glycidol was converted to alcohol 16 by epoxide opening with n-pentyl cuprate and subsequent chelation-controlled allylation.…”

“…Since Marco et al achieved the first synthesis of microcarpalide, 22) a number of syntheses have been reported. Similarly to Marco's synthesis, most of them also featured RCM of a diene ester of type 18.…”

“…Banwell's group (2004, entmicrocarpalide), 44) Chavan's group (2005), 45) and Fürst-ner's group (2007) 46) employed precursor 18 (or ent-18), the same intermediate as in Marco's synthesis. 22,23) Synthesis of ent-microcarpalide by Banwell and Loong is shown in Scheme 2 [5]. 44) They constructed the intermediate ent-18 by cross metathesis 4,19) of , -unsaturated ester 44 using 2nd-generation Grubbs catalyst 20) under ethylene, because direct methylenation of hemiacetal 43 (conversion to ent-18) was not successful, and RCM of , -unsaturated ester 44 did not proceed.…”