Enantioselective total synthesis of (-)-microcarpalide

被引：33

作者：

Davoli, P ^{[1
]}

Fava, R ^{[1
]}

Morandi, S ^{[1
]}

Spaggiari, A ^{[1
]}

Prati, F ^{[1
]}

机构：

[1] Univ Modena, Dipartimento Chim, I-41100 Modena, Italy

来源：

TETRAHEDRON | 2005年 / 61卷 / 18期

关键词：

fungal metabolites; nonenolides; actin-targeting compounds; microfilament disrupting activity; asymmetric homologation; boronic esters; ring-closing metathesis;

D O I：

10.1016/j.tet.2005.02.069

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

The enantioselective total synthesis of the actin-targeting metabolite (-)-microcarpalide is described. Key steps include ring-closing metathesis (RCM) for the final construction of the 10-membered lactone framework and stereoselective homologation of boronic esters for the insertion of all stereocentres with the desired absolute configuration. In particular, the acidic fragment was prepared in seven steps from a suitable chiral bromomethane boronate by means of two sequential stereoselective homologations to install the two stereocentres with the correct final R stereochemistry, employing (-)-pinanediol as the chiral director. Subsequent elaboration to the required C-7 backbone entailed nucleophilic displacement with a vinyl Grignard reagent, oxidative cleavage of the boronic scaffold and protection-deprotection manipulations. Interestingly, when the tribenzyloxy diene ester resulting from DCC-mediated coupling of the two key synthons was subjected to RCM in the presence of Grubbs' catalyst, the reaction proceeded stereoselectively to yield the desired trans oxecin-2-one, albeit with poor conversion. (c) 2005 Elsevier Ltd. All rights reserved.

引用

页码：4427 / 4436

页数：10

共 53 条

[1]

Armstrong SK, 1998, J CHEM SOC PERK T 1, P371

[2]

Banwell MG, 2004, HETEROCYCLES, V62, P713

[3] Synthesis of novel simplified eleutheside analogues with potent microtubule-stabilizing activity, using ring-closing metathesis as the key-step [J].