Total synthesis of ('+ or -')- 2-amino- 1,3-propanediols and the styryl-lactones ('+ or -')- Leiocarpin A and ('+ or -')- Goniodiol

Author(s)

Paulo Henrique de Souza Paioti

• Document type: Master's Dissertation
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Instituto de Química
• Defense date: 2011-07-22

Examining board members

Fernando Antonio Santos Coelho; Luiz Carlos Dias; Giovanni Wilson Amarante

• Advisor: Fernando Antonio Santos Coelho

Abstract

We report herein new synthetic applications of the Morita-Baylis-Hillman (MBH) reaction. Initially, we have described a new diastereoselective approach to substituted 2-amino-1,3-propanediols from MBH adducts. These structural moieties have been widely used as intermediates of several compounds with relevant pharmacological and synthetic interests. In this work, 2-amino-1,3-propanediols with anti relative stereochemistry were readily prepared via reductive amination of 2-oxo-1,3-propanediols MBH adducts derivatives. The diastereoselectivity of the reductive amination step was indirectly confirmed as leading the synthesis of oxazolidin-2-ones cores. In order to establish the relative stereochemistry of these oxazolidin-2-ones, NMR experiments, based on nuclear Overhauser effect (nOe), and comparison with the literature data, were successfully performed. We have also reported a total synthesis of (±)-Leiocarpin A and (±)-Goniodiol. These natural products belong to the class of styryl-lactones, a new type of interesting substances which have been isolated from Goniothalamus genus of plants. These compounds present potential citotoxicity and selectivity against different types of human tumor cells. In a straightforward strategy, a MBH adduct proceeded a common intermediate, disilyloxyaldehyde, that resulted in the target compounds, (±)-Leiocarpin A and (±)-Goniodiol. Finally, we described a diastereoselective synthesis of (±)-Leiocarpin A based on a selective allylation reaction (AU)

• FAPESP's process: 09/03995-8 - Preparation of substituted alpha-amino-beta-hydroxy esters e 2-amino-1,3-diols from Morita-Baylis-Hillman adducts.
• Grantee: Paulo Henrique de Souza Paioti
• Support Opportunities: Scholarships in Brazil - Master