RESUMO
A general protocol to independently access stereoisomerically pure ß'-hydroxy-ß-amino acid derivatives that is based on dibutylboron triflate-mediated aldol reaction of suitably protected ß-amino acids bearing chiral oxazolidinone auxiliary is reported. The method smoothly afforded syn-aldol (α,ß'-syn) products in pure form and excellent isolated yield. Both α,ß-syn and α,ß-anti isomers are readily accessible solely through the choice of the oxazolidinone chirality. This method allows for the preparation of stereoisomeric ß'-hydroxy-ß-amino acid derivatives that were previously unreported.
Assuntos
Aldeídos/química , Aminoácidos/química , Catálise , Técnicas de Química Combinatória , Ésteres/química , Estrutura Molecular , EstereoisomerismoRESUMO
Methyl-branched (Z)-trisubstituted olefins are found in many polyketides with interesting biological activity, such as epothilone D (1), discodermolide (3), and peloruside A (2). Despite the employment of numerous different strategies, this motif has often been the weak point in total synthesis. Thus, we present a novel hydroxide- induced Grob-type fragmentation as an easy access to trisubstituted olefins. In our case, beta-mesyloxy delta-lactones with three stereogenic centers were chosen whose fragmentation underlies a high stereoelectronic control. Major challenges in the syntheses were the installation of quaternary stereocenters, achieved by enzymatic desymmetrization of meso-diesters and by aluminium-promoted stereoselective rearrangement of chiral epoxides, respectively. Different aldol strategies were developed for the formation of the fragmentation precursors. Additionally a short survey about nucleophilic additions to aldehydes with quaternary alpha-centers is presented.
Assuntos
Alcanos/síntese química , Alcenos/síntese química , Compostos Bicíclicos Heterocíclicos com Pontes/síntese química , Carbamatos/síntese química , Epotilonas/síntese química , Lactonas/síntese química , Pironas/síntese química , Alcanos/química , Alcenos/química , Compostos Bicíclicos Heterocíclicos com Pontes/química , Carbamatos/química , Epotilonas/química , Lactonas/química , Estrutura Molecular , Pironas/química , EstereoisomerismoRESUMO
Discriminating elimination: A new method for the synthesis of methyl-branched trisubstituted Z olefins, a structural motif in many polyketides with anticancer activity, relies on an (-)OH-induced decarboxylative Grob-type fragmentation (see scheme; Ms = mesyl). The starting materials are beta-mesyloxy lactones with a quaternary alpha center, which are prepared by aldol reactions in a diastereo- and enantioselective manner.
