Evolution of a Strategy for Concise Enantioselective Total Synthesis of the Salinosporamide Family of Natural Products.
Angew Chem Int Ed Engl
; 61(41): e202210317, 2022 10 10.
Article
em En
| MEDLINE
| ID: mdl-35982530
ABSTRACT
Our first strategy for rapidly accessing pyrrolidinone cores of salinosporamides involved combined use of memory of chirality and dynamic kinetic resolution principles in aldol reactions of the serine-derived 5-oxazolidinone substrate, which was ultimately unsuccessful with respect to enantioselectivity. This failure led us to the revised strategy. The influence of the stereocenter in 5-oxazolidinone enabled selective installation of the C-2 stereocenter. The intramolecular aldol reaction of the C-2 stereodefined aldol substrate was successful. An unexpected hydrolytic dynamic kinetic resolution was observed in hydrolyses of the bicyclic aldol products. This unprecedented substrate-driven hydrolytic dynamic kinetic resolution was utilized in preparing the pyrrolidinone core with excellent efficiency. Through this strategy, the concise total syntheses of salinosporamides A and B as well as cinnabaramides A, E, and F were achieved with high selectivity.
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Base de dados:
MEDLINE
Assunto principal:
Produtos Biológicos
/
Oxazolidinonas
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article