Synthesis of Some 3-Aryl-1,2,4-oxadiazoles Carrying a Protected L-Alanine Side Chain

Abstract

A síntese de alguns derivados dos 1,2,4-oxadiazóis (4a-d) partindo das arilamidoximas apropriadas (1a-d) e do ácido N-t-butoxycarbonil-O-benzil-L-aspártico é descrita. As estruturas destes novos compostos foram determinadas por meios espectroscópicos.The synthesis of some 1,2,4-oxadiazole derivatives (4a-d) starting from arylamidoximes 1a-d and N-t-butoxycarbonyl-O-benzyl-L-aspartic acid is described. The structures of these new products have been determined by spectroscopic methods.

Oxadiazoles

“…Research on this class of heterocycles has registered great interest in medicinal chemistry. Many derivatives possess diverse biological activities [121][122][123]. Some 1,2,4-oxadiazoles can reduce pain and inflammation in rats and mice [124,125]; for example, N-[3-aryl-1,2,4-oxadiazol-5-yl-methyl]phthalimides have been found to be analgesic, and one of them, namely, N-[3-phenyl-1,2,4-oxadiazol-5-yl-methyl]phthalimide, possesses highly enhanced analgesic activity compared to aspirin [124].…”

Synthesis of new 1,2,4-oxadiazoles carrying (1'S,2'S)-t-butyloxycarbonyl-1-amino-2- methyl-1-butyl and (1'S)-t-butyloxycarbonyl-1'-amino-1'-ethyl groups at C-5

“…Since the reaction conditions in the present work are mild and similar to the one reported earlier, 10 it is assumed that no racemization occurred during the synthesis of these 1,2,4-oxadiazoles. This conclusion is supported by the 1 H NMR spectra, which showed the presence of only one H-3 absorption for 3a-f; had there been racemization, one would expect two diastereomers hence more than one absorption.…”

“…We have already published one paper relating to the synthesis of 3-aryl-1,2,4-oxadiazoles carrying a protected L-alanine side chain, starting from arylamidoximes and protected aspartic acid, 10 and it has been established that the products obtained from the condensation of arylamidoximes and an appropriately protected amino acid didn't lead to isomerization. Applying a similar strategy, but using Bocprotected L-isoleucine or L-alanine and arylamidoximes, we synthesized seven 1,2,4-oxadiazoles, six containing two asymmetric centers 4a-f and one oxadiazole having only one asymmetric center 6, as shown below (Scheme 1).…”

Mass spectrometric analysis of 1,2,4‐Oxadiazoles and 4,5‐Dihydro‐1,2,4‐Oxadiazoles

“…Two of our recent publications contain references which describe the pharmacological and other interesting properties of substituted 1,2,4-oxadiazoles (De Melo et al, 1998;Srivastava et al, 1999). New 1,2,4-oxadiazoles, prepared by us, are able to reduce pain and inflammation in rats and mice (Antunes et al, 1998;Srivastava et al, 2000).…”