Total synthesis of (-)-microcarpalide, a novel microfilament disrupting metabolite.
The stereoselective total synthesis of (-)-microcarpalide, a recently discovered 10-membered lactone of fungal origin displaying a remarkable disrupting action on actin microfilaments, was accomplished by using ring-closing metathesis (RCM) as the key step for the formation of the medium-sized ring. The diene ester required for the macrocyclization reaction was assembled via DCC-mediated esterification of two suitable partners, each bearing a terminal alkene group. The alcohol fragment was synthesized from n-bromohexane through a seven-step sequence entailing two consecutive stereoselective homologations of chiral boronic esters as strategic transformations for the sequential insertion of the two stereocentres with the final S absolute configuration, using (+)-pinanediol as the chiral director; final elaboration to the desired C(11) framework envisaged treatment with an allyl Grignard reagent and oxidative cleavage of the boronic scaffold. In contrast, the acidic fragment was prepared in ten steps from d-tartaric acid, whose C(4) backbone was elongated to the required C(7) skeleton by means of two distinct Swern-Wittig oxidation-homologation sequences.
Davoli
Paolo
P
Dipartimento di Chimica, Università di Modena e Reggio Emilia, via Campi 183, I-41100 Modena, Italy. davoli.chemistry@unimo.it
Spaggiari
Alberto
A
Castagnetti
Luca
L
Prati
Fabio
F
D008841:Actin Cytoskeleton / Q000187:drug effects; D000473:Alkanes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006573:Heterocyclic Compounds, 1-Ring / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism
D000473:Alkanes; D006573:Heterocyclic Compounds, 1-Ring; C442266:microcarpalide