RESUMO
In this work we present an efficient, environmentally friendly approach to the synthesis of a series of hyodeoxycholic acid derivatives applying Biocatalysis. Fifteen acetyl and ester derivatives, twelve of them new, were obtained through an enzymatic strategy in a fully regioselective way and in very good to excellent yield. In order to find the optimal reaction conditions, the influence of several parameters such as enzyme source, alcohol or acylating agent:substrate ratio, enzyme:substrate ratio, temperature and reaction solvent was considered. The excellent results obtained made this procedure very efficient, particularly considering the low amount of enzyme required. In addition, this methodology uses mild reaction conditions and has reduced environmental impact, making biocatalysis a suitable way to obtaining these bile acids derivatives.
Assuntos
Biocatálise , Ácido Desoxicólico/química , Ácido Desoxicólico/síntese química , Lipase/metabolismo , Acetilação , Candida/enzimologia , Técnicas de Química Sintética , EsterificaçãoRESUMO
Natural brassinosteroids are widespread in the plant kingdom and it is known that they play an important role in regulating plant growth. In this study, two new brassinosteroid analogs with shorter side chains but keeping the diol function were synthesized. Thus, the synthesis of 2-deoxybrassinosteroids analogs of the 3α-hydroxy-24-nor, 22,23-dihydroxy-5α-cholestane side chain type is described. The starting material is a derivative from hyodeoxycholic acid (4), which was obtained with an overall yield of 59% following a previously reported five step route. The side chain of this intermediate was modified by oxidative decarboxylation to get a terminal olefin at the C22-C23 position (compound 20) and subsequent dihydroxylation of the olefin. The resulting epimeric mixture of 21a, 21b was separated and the absolute configuration at the C22 carbon for the main product 21a was elucidated by single crystal X-ray diffraction analysis of the benzoylated derivative 22. Finally, lactonization of 21a through a Baeyer-Villiger oxidation of triacetylated derivative 23, using CF3CO3H/CHCl3 as oxidant system, leads to lactones 24 and 25 in 35% and 14% yields, respectively. Deacetylation of these compounds leads to 2-deoxybrassinosteroids 18 and 19 in 86% and 81% yields. Full structural characterization of all synthesized compounds was achieved using their 1D, 2D NMR, and HRMS data.