O piridoxal como precursor de intermediários sintéticos protegidos e halogenados, potenciais blocos de construção de diversidade molecula

Abstract

The reactivity of pyridoxal (PL), pyridoxine (PN) and a furopyridine obtained from pyridoxal against iodination reactions was studied, aiming to obtain vitamin B6 derivatives that can be used as substrates in cross-coupling reactions. The iodination occurred at the C6 carbon of the pyridine ring, and the iodinated derivatives were obtained with yields ranging from 25−73%. The iodinated PL and furopyridine are both novel compounds. In order to obtain precursors of heterocyclic compounds derived from vitamin B6, the work also aimed to obtain chalcones by the Claisen−Schmidt condensation reaction of PL and methylketones. Accordingly, several tests were carried out to protect the PL hydroxymethyl group to prevent the previously reported oxa−Michael addition that would leave to the formation of furopyridines in detriment of chalcones. Attempts to protect the hydroxymethyl group with MsCl, TsCl and Ac2O under several conditions have led to monoprotected and diprotected products in the form of cyclic hemiacetal that are unprecedented in the literature. Reactions involving the hydroxymethyl group of PL with the TMSCl group led to the recovery of part of the substrates used in the reaction and the formation of unidentified products and/or by products. Protection with TBDMSCl from a methodology adapted from the literature, using CH2Cl2 as solvent, imidazole as base, and 3 equivalents of the protection agent led to the selective protection of the hydroxymethyl group in 66% yield. A series of 11 new chalcones was then obtained from the reaction of the protected PL with different ketones. The reaction was carried out in basic medium (NaOH) with EtOH as solvent at room temperature and yields ranged from 53−76%. All compounds were characterized by EMAR, IR and RMN.