A Highly Convergent Approach toward (−)-Brevenal

Abstract

Progress toward a highly convergent, asymmetric synthesis of brevenal is reported. Construction of the AB-ring and E-ring cyclic ether fragments was achieved through asymmetric alkylation/ring-closing metathesis strategies. A Horner-Wadsworth-Emmons olefination was used in a key bond-forming step to couple the advanced cyclic fragments and enable rapid access to the AB-E ring system.

Synthesis and biological evaluation of new piplartine analogues as potent aldose reductase inhibitors (ARIs)

“…Hydrolysis of 7 in the presence of LiOH followed by condensation with 9 in the presence of n -BuLi/pivalyl chloride in THF afforded the piplartine in good yields (65%) [16]. The key intermediate 9 was prepared in a two step sequence starting from homoallylamine 10 , which is condensed with acryl chloride to give 11 , subsequent ring closing metathesis (RCM) reaction of 11 using Grubbs II catalyst [17]. …”

Towards Allopumiliotoxins: A Concise Synthesis of the Indolizidine Core

“…[9] This reaction allowed us to install the tertiary asymmetric carbon atom with the required stereochemistry. Methyl ester 11 was obtained in 92 % yield by oxidative cleavage of 6 followed by treatment with diazomethane.…”

Recent Applications of the Horner-Wadsworth-Emmons Reaction to the Synthesis of Natural Products

“…The same author had previously reported a synthesis of the BCDE fragment of the toxin by a similar approach [77]. In 2010 Crimmins reported the synthesis of a putative precursor for (-)-Brevenal [78], which paradoxically behaves as a brevitoxine antidote and as a potential therapeutic agent for cystic fibrosis. A barium hydroxide promoted HWE reaction between phosphonomethylketone 50a and aldehyde 50b was used to establish the C and D ring precursor tether in 50c (Scheme 50).…”