Carbonylative coupling reactions involving C2-glycosides

Author(s)

Mariana Pompílio Darbem Rocha

• Document type: Doctoral Thesis
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Conjunto das Químicas (IQ e FCF) (CQ/DBDCQ)
• Defense date: 2021-07-22

Examining board members

Helio Alexandre Stefani; Antonio Luiz Braga; Nelson Luis de Campos Domingues; Alcindo Aparecido Benito dos Santos

• Advisor: Helio Alexandre Stefani

Abstract

α,β-unsaturated sugars derivatives are particularly valuable, and they are prone to undergo various chemical transformations. In this context, many natural products can be synthesized following different strategies. Inspired by the rich chemistry of glycals, this work reports methodologies for the functionalization of glycais in the carbonylative synthesis of amidoglycals, glucal esters, glycoalkynones, glyco-thioesters, glyco-selenoesters and glyco-chalcones, which can be attractive to study their biological activities. This thesis was divided into 6 chapters and aimed at the use of molybdenum hexacarbonyl Mo(CO)6 as a solid source of carbon monoxide. In the first chapter the synthesis of the starting materials is presented. The second chapter describes how to obtain amidoglucal and glucal esters from 2-iodo-3,4,6-tri-O-acetyl-D-glucal as a substrate. The synthetic viability of this methodology was shown with satisfactory yields, 29 compounds were obtained with yields that varied from 40-98%. Chapter 3 is dedicated to the synthesis of D-glycoalkynones, the methodology, showed advantages over several others reported in the literature, such as shorter reaction times, milder temperatures in a one pot procedure. It was possible to obtain 18 compounds with yields between 43-99%, with an additional functionalization to obtain D-glyco-1,2,3-triazoles. In chapter 4, the synthesis of thioesters and selenestesters were depicted, 23 thioesters and 6 selenestesters were obtained with moderate to excellent yields. Some compounds derived from thioester have been subjected to biological tests on tumor cells and preliminary tests have shown promise. In this chapter the methodology presented was the first example of carbonylative coupling of nucleophilic species of selenium with carbon nucleophiles (2-iodoglycal). Chapter 5 is dedicated to the synthesis of 2-ketoglycosides through the Heck carbonylative reaction catalyzed by Pd. Different 2-iodoglicals were compatible with the reaction conditions and a total of 19 different enones were synthesized with up to 89% yield. Finally, in Chapter 6, a simple protocol was developed to obtain unprotected glyco-alkynones with moderate to excellent yields through the use of Mo(CO)6 as a catalyst, in addition to glyco-flavones from the cyclization with AuCl3, with yields between (44-77%). Glyco-flavones are compounds with potential activity against Alzheimer\'s. (See scheme in PDF file) (AU)

• FAPESP's process: 16/24396-9 - Triazolic 2-Aryloxazolines: synthesis of small libraries, biological activity, fluorescence and ligands
• Grantee: Mariana Pompilio Darbem Rocha
• Support Opportunities: Scholarships in Brazil - Doctorate