β 3 -肾上腺素能受体激动剂Vibegron的实用和可扩展合成方法

IF 2.5 3区化学 Q2 CHEMISTRY, ORGANIC

European Journal of Organic Chemistry Pub Date : 2025-06-23 DOI:10.1002/ejoc.202500469

Prakash Kumar, Santanu Karmakar, Prathama S. Mainkar, Rudrakshula Madhavachary, Srivari Chandrasekhar

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引用次数: 0

摘要

利用现成的4-硝基- d -苯丙氨酸和(R)-扁桃酸，开发了一种实用且可扩展的β3-肾上腺素受体激动剂Vibegron的合成方法。该合成具有关键酸催化的n -酰基胺离子环化和高度非对映选择性还原的特点，能够高效地构建顺式2,5-二取代吡咯烷核心。最后用市售的吡咯嘧啶钠盐进行酰胺化，使Vibegron的总收率很高。

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A Chiron Approach to the Practical and Scalable Synthesis of the β₃-Adrenergic Receptor Agonist Vibegron

A practical and scalable synthesis of the β3-adrenergic receptor agonist Vibegron has been developed using a streamlined chiral-pool approach from readily available 4-nitro-D-phenylalanine and (R)-mandelic acid. The synthesis features a key acid-catalyzed N-acyl iminium ion cyclization followed by a highly diastereoselective reduction, enabling efficient construction of the cis-2,5-disubstituted pyrrolidine core. Final amidation with a commercially available pyrrolopyrimidine sodium salt furnished Vibegron in excellent overall yield.

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来源期刊

European Journal of Organic Chemistry 化学-有机化学

CiteScore

5.40

自引率

3.60%

发文量

752

审稿时长

1 months

期刊介绍： The European Journal of Organic Chemistry (2019 ISI Impact Factor 2.889) publishes Full Papers, Communications, and Minireviews from the entire spectrum of synthetic organic, bioorganic and physical-organic chemistry. It is published on behalf of Chemistry Europe, an association of 16 European chemical societies. The following journals have been merged to form two leading journals, the European Journal of Organic Chemistry and the European Journal of Inorganic Chemistry: Liebigs Annalen Bulletin des Sociétés Chimiques Belges Bulletin de la Société Chimique de France Gazzetta Chimica Italiana Recueil des Travaux Chimiques des Pays-Bas Anales de Química Chimika Chronika Revista Portuguesa de Química ACH—Models in Chemistry Polish Journal of Chemistry.