A Scalable Approach for the Synthesis of Epothilone Thiazole Fragment (C12–C21 unit) Via Wacker Oxidation

Rajashekar Kommera; Venkateshwer Reddy Kasireddy; Venkat Reddy Ghojala; Markandeya Bekkam; Pradeep Rebelli; Jayaprakash Rao Yerrabelly

doi:10.1055/s-0036-1591942

Synlett, Table of Contents

Synlett 2018; 29(08): 1076-1078
DOI: 10.1055/s-0036-1591942

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A Scalable Approach for the Synthesis of Epothilone Thiazole Fragment (C₁₂–C₂₁ unit) Via Wacker Oxidation

Rajashekar Kommera

^aDepartment of Chemistry, Jawaharlal Nehru Technological University College of Engineering, Hyderabad 500085, India

^bDepartment of Research and Development, MSN R&D Center, Pashamylaram, Medak, Telangana 502307, India

,

Venkateshwer Reddy Kasireddy

^cDepartment of Chemistry, CMR Engineering College, Jawaharlal Nehru Technological University, Hyderabad 501401, India

,

Venkat Reddy Ghojala

^bDepartment of Research and Development, MSN R&D Center, Pashamylaram, Medak, Telangana 502307, India

,

Markandeya Bekkam

^bDepartment of Research and Development, MSN R&D Center, Pashamylaram, Medak, Telangana 502307, India

,

Pradeep Rebelli

^bDepartment of Research and Development, MSN R&D Center, Pashamylaram, Medak, Telangana 502307, India

,

Jayaprakash Rao Yerrabelly*

^dDepartment of Chemistry, University College of Science, Saifabad, Osmania University, Hyderabad 500004, India

^eDepartment of Organic Chemistry, Telangana University, Nizamabad, Telangana 503322, India Email: yjpr_19@yahoo.com

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Abstract

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Abstract

A new scalable synthesis of the common thiazole fragment (C₁₂–C₂₁ unit) of epothilone family of molecules (epothilone A–D) has been developed via palladium-catalyzed Wacker oxidation as a key step using (S)-2,2,3,3,9,9,10,10-octamethyl-5-vinyl-4,8-dioxa-3,9-disilaundecane, which has been prepared from commercially available chiral synthon (R)-ethyl-4-cyano-3-hydroxybutanoate. Then further chemical modifications using Horner–Wadsworth–Emmons reaction and Wittig reaction result in the common thiazole fragment (C₁₂–C₂₁ unit) in good yields.

Key words

thiazole fragment - epothilone - Wacker oxidation - ixabepilone - C₁₂–C₂₁ unit of epothilone

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References

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