Recent Advances in the Synthesis of Oxazole-Based Molecules via van Leusen Oxazole Synthesis

Abstract

Oxazole compounds, including one nitrogen atom and one oxygen atom in a five-membered heterocyclic ring, are present in various biological activities. Due to binding with a widespread spectrum of receptors and enzymes easily in biological systems through various non-covalent interactions, oxazole-based molecules are becoming a kind of significant heterocyclic nucleus, which have received attention from researchers globally, leading them to synthesize diverse oxazole derivatives. The van Leusen reaction, based on tosylmethylisocyanides (TosMICs), is one of the most appropriate strategies to prepare oxazole-based medicinal compounds. In this review, we summarize the recent advances of the synthesis of oxazole-containing molecules utilizing the van Leusen oxazole synthesis from 1972, aiming to look for potential oxazole-based medicinal compounds, which are valuable information for drug discovery and synthesis.

Keywords: TosMICs; oxazole; synthesis; van Leusen.

Scheme 1

General van Leusen synthesis base on tosylmethylisocyanides (TosMICs).

Scheme 2

The first example of van Leusen oxazole synthesis.

Scheme 3

Mechanism of van Leusen oxazole synthesis.

Scheme 4

Synthesis of 5-aryloxazoles 31.

Scheme 5

Synthesis of methylketone 33 via aryl-substituted TosMIC reagent.

Scheme 6

The reaction of 3/2-formylindoles with TosMIC and 34.

Scheme 7

The reaction of 3/2-formylindoles with TosMIC and 37.

Scheme 8

Synthesis of C₂- and C₃-symmetric oxazole derivatives 41, 43, and 45.

Scheme 9

A one-pot synthesis of 4,5-disubstituted oxazoles 48 in ionic liquid.

Scheme 10

Synthesis of naphthoxazoles and fused heterobenzoxazoles 51, trans-5-(2-vinylstyryl)oxazole 53, and 5-(arylethenyl)oxazoles 55.

Scheme 11

Synthesis of BOxaPy 59.

Scheme 12

Synthesis of potential anticancer drug TOxaPy 61.

Scheme 13

Synthesis of potential artificial compound 64.

Scheme 14

The marine natural product streptochlorin analogue 66.

Scheme 15

Synthesis of ‘propeller-like’ anticancer biomolecular target 68.

Scheme 16

Synthesis of flexible tripodal 1,3-oxazoles 70 as molecular scaffolds.

Scheme 17

A novel modified van Leusen strategy for the synthesis of 73.

Scheme 18

Synthesis of POPOP structural isomers 76 and 79.

Scheme 19

Synthesis of 81 by modified van Leusen reaction using green media.

Scheme 20

Synthesis of C₃-symmetric star-shaped molecules 83.

Scheme 21

Synthesis of heterocyclic systems derivatives 85 and 87 based on TosMIC.

Scheme 22

Synthesis of ‘head-to-tail’-connected asymmetric pyridyl-oxazoles 93 for anticancer purposes.

Scheme 23

Synthesis of C₅-substituted oxazoles 95, 96, and 97.

Scheme 24

Synthesis of pyrimidine derivative 99.

Scheme 25

Synthesis of p- and m-position products 102.

Scheme 26

Synthesis of 5-(2-tosylquinolin-3-yl)oxazole 104.

Scheme 27

Synthesis of inhibitor of microbial pathogen 106.