Multi-Gram Synthesis of Enantiopure 1,5-Disubstituted Tetrazoles Via Ugi-Azide 3-Component Reaction.

Pietro Capurro,Lisa Moni,Christian Mang,Andrea Galatini,Andrea Basso

doi:10.3390/molecules23112758

Pietro Capurro, Lisa Moni + Show 3 more

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https://doi.org/10.3390/molecules23112758

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Journal: Molecules (Basel, Switzerland)	Publication Date: Oct 25, 2018
Citations: 12	License type: CC BY 4.0

Affiliation: University of Genoa

Abstract

Tetrazoles have been widely studied for their biological properties. An efficient route for large-scale synthesis of 1,5-disubstituted tetrazoles (1,5-DTs) is presented. The strategy exploits a reductive approach to synthetize a cyclic chiral imine substrate which is then converted into the target product through an Ugi-azide three-component reaction (UA-3CR). The final products are equipped with additional functionalities which can be further elaborated for the generation of combinatorial libraries of enantiopure heterocycles.

Highlights

Since their discovery in 1885, tetrazoles have been widely studied, and their chemistry and biological properties have been deeply explored
We have recently reported that cyclic chiral imines, which are synthetized via reduction
We have have recently recently reported reported that that cyclic cyclic chiral chiral imines, imines, which which are are synthetized synthetized via reduction of the corresponding lactam with Schwartz’s reagent, can be employed in the Betti reaction with of the corresponding lactam with Schwartz’s reagent, can be employed in the Betti reaction with phenol derivatives [12]

Summary

Introduction

Since their discovery in 1885, tetrazoles have been widely studied, and their chemistry and biological properties have been deeply explored. 1,5-DTs have shown biological activity as HIV-protease inhibitors (e.g., analogues of Saquinavir are currently being studied), but they have been proved to be good candidates for new antiseptic, anti-inflammatory, and analgesic drugs. Classical synthetic methods hardly permit differently functionalized products featuring a common scaffold to be obtained, and a method to straightforwardly access complex structures with different decorations is highly desirable. Within this field, multicomponent reactions (MCRs) are a powerful tool that can be exploited to synthetize a plethora of potentially active structures with few steps and relatively simple building blocks [3,4,5]

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Conclusion