Synlett
DOI: 10.1055/a-2587-7778
letter
Emerging Trends in Organic Chemistry: A Focus on India

Synthesis of Sacubitril Isomers Governed by Differential Facial Selectivity during the Hydrogenation of Conjugated System

Sreenivasulu Kurella
a   API R&D, IPDO, Dr. Reddy′s Laboratories Ltd. Bachupally, Hyderabad, Telangana-500090, India
b   Department of Chemistry, Osmania University, Hyderabad, Telangana-5000007, India
,
Phani Mamidipalli
a   API R&D, IPDO, Dr. Reddy′s Laboratories Ltd. Bachupally, Hyderabad, Telangana-500090, India
,
Sampath Alla
a   API R&D, IPDO, Dr. Reddy′s Laboratories Ltd. Bachupally, Hyderabad, Telangana-500090, India
,
Neha Kumari
c   Department of Chemistry Birla Institute of Technology, Mesra, Ranchi, Jharkhand-835215, India
,
Prabhakar Reddy V
b   Department of Chemistry, Osmania University, Hyderabad, Telangana-5000007, India
,
Ashoke Sharon
c   Department of Chemistry Birla Institute of Technology, Mesra, Ranchi, Jharkhand-835215, India
,
Srinivas Achanta
a   API R&D, IPDO, Dr. Reddy′s Laboratories Ltd. Bachupally, Hyderabad, Telangana-500090, India
,
Rakeshwar Bandichhor∗
a   API R&D, IPDO, Dr. Reddy′s Laboratories Ltd. Bachupally, Hyderabad, Telangana-500090, India
› Author Affiliations
We thank the management of Dr. Reddy’s laboratories Limited for supporting this work.
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Abstract

A stereoselective process for the synthesis of sacubitril isomers with high yield is reported. Previously reported preparation of these isomers is cumbersome, requiring isolation by repetitive fractional crystallization from the mother liquors remaining after the separation of the major diastereomers (sacubitril) and its enantiomer, respectively. The key feature in our approach is a reversal of stereoselectivity during the catalytic hydrogenation of β,γ-ene amino acid by altering the protecting group on nitrogen. This led to the formation of isomers as the major products providing rapid access to multigram quantities of sacubitril isomers.

Key words

sacubitril isomers - impurities synthesis - facial selectivity - transition state - spectral analysis

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/a-2587-7778. Single-crystal X-ray diffraction data and files for compound 1 (CCDC2453255)
  • Supporting Information


Publication History

Received: 25 February 2025

Accepted after revision: 14 April 2025

Accepted Manuscript online:
14 April 2025

Article published online:
28 May 2025

© 2025. Thieme. All rights reserved

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