Application of Isayama-Mukaiyama cobalt catalyzed hydroperoxysilylation for the preparation of ritonavir hydroperoxide | Health & Environmental Research Online (HERO)

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Citation
Tags

HERO ID

4812526

Reference Type

Journal Article

Title

Application of Isayama-Mukaiyama cobalt catalyzed hydroperoxysilylation for the preparation of ritonavir hydroperoxide

Author(s)

Gazal, S; Gupta, P; Gunturu, SR; Isherwood, M; Voss, ME

Year

2016

Is Peer Reviewed?

Journal

Tetrahedron Letters
ISSN: 0040-4039
EISSN: 1873-3581

Publisher

Elsevier Ltd

Volume

Issue

Page Numbers

5099-5102

Language

English

DOI

10.1016/j.tetlet.2016.10.022

Web of Science Id

WOS:000386862000019

Abstract

We report the preparation of thiazol-5-ylmethyl ((2S,3S,5S)-5-((S)-2-(3-((2-(2-hydroperoxypropan-2-yl) thiazol-4-yl)methyl)-3-methylureido)-3-methylbutanamido)-3-hydroxy-1,6-diphenylhexan-2-yl)carba-mate, a hydroperoxide impurity of ritonavir also known as ritonavir USP impurity G. Due to the complexity of ritonavir's structure and abundance of oxidation susceptible functional groups, forced degradation was found to be a non-selective and inadequate tactic. Therefore, a multistep synthesis was applied. The overall strategy involved initial introduction of a propenyl moiety to the terminal thiazole which enabled selective oxidation using Co(thd)(2) (0.1 equiv)/O-2 (Isayama-Mukaiyama cobalt catalyzed hydroperoxysilylation) following structural assembly. (C) 2016 Published by Elsevier Ltd.

Keywords

Ritonavir hydroperoxide; Isayama-Mukaiyama hydroperoxysilylation; TES stoichiometry; Late stage oxidation; Cobalt