Exploiting the synthetic potentiality of the Morita-Baylis-Hillman reaction towards the synthesis of vicinal tricarbonyl compounds and cyclopenta[b]indole derivatives

Author(s)

Marilia Simão dos Santos

• Document type: Master's Dissertation
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Instituto de Química
• Defense date: 2012-02-28

Examining board members

Fernando Antonio Santos Coelho; Lucia Helena Brito Baptistella; Paulo Roberto Ribeiro Costa

• Advisor: Fernando Antonio Santos Coelho

Abstract

The synthetic potential of Morita-Baylis-Hillman adducts was exploited towards the development of a new strategy for the preparation of vicinal tricarbonyl compounds and cyclopenta [b] indole derivatives. The vicinal tricarbonyl compounds represent a structural pattern of great synthetic interest because they are employed in the synthesis of heterocycles and several biologically active compounds. The three steps methodology involves the the preparation of MBH adducts, followed by two subsequent oxidations. The route proved to be fast, simple and efficient, with overall yields ranging from 15 to 75%. This strategy is operationally ease and sustainable, since a low level of waste is generated. The nuclei cyclopenta [b]indoles are present in the structure of some natural products and bioactive compounds. This has stimulated efforts towards the development of new synthetic routes to prepare this heterocyclic pattern. Our strategy is based on the oxidation of MBH adduct followed by Michael addition using indole as nucleophile to provide a substituted b-ketoester. The keto carbonyl was reduced and the substituted b-hydroxyester was therefore cyclized in acid conditions leading the desired heterocycles. The synthesis was highly diastereoselectivity and mechanism of the cyclization step was monitored by mass spectrometry. The compounds were evaluated against some tumor cell lines exhibiting promising cytotoxic activity (AU)

• FAPESP's process: 10/04716-2 - Synthetic uses of Morita-Baylis-Hillman adducts: new approach to the synthesis of vicinal tricarbonyl compounds
• Grantee: Marília Simão dos Santos
• Support Opportunities: Scholarships in Brazil - Master