Practical Asymmetric Synthesis of Sitagliptin Phosphate Monohydrate

Optically pure sitagliptin phosphate monohydrate is efficiently and practically synthesized through a chiral hemiacetal as the key intermediate in 54% overall yield starting from (E)-4-(2,4,5-trifluorophenyl)but-2-enal and N-boc-protected hydroxylamine. The chiral hemiacetal fragment is constructed...

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Detalles Bibliográficos
Autores principales: Gao, Haoling, Yu, Jiangang, Ge, Chengsheng, Jiang, Qun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6099835/
https://www.ncbi.nlm.nih.gov/pubmed/29899310
http://dx.doi.org/10.3390/molecules23061440
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author Gao, Haoling
Yu, Jiangang
Ge, Chengsheng
Jiang, Qun
author_facet Gao, Haoling
Yu, Jiangang
Ge, Chengsheng
Jiang, Qun
author_sort Gao, Haoling
collection PubMed
description Optically pure sitagliptin phosphate monohydrate is efficiently and practically synthesized through a chiral hemiacetal as the key intermediate in 54% overall yield starting from (E)-4-(2,4,5-trifluorophenyl)but-2-enal and N-boc-protected hydroxylamine. The chiral hemiacetal fragment is constructed by a tandem aza-Michael/hemiacetal reaction catalyzed by an organocatalyst and the influence of acidity of Brønsted acid on tandem aza-Michael/hemiacetal reaction is researched in detail.
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spelling pubmed-60998352018-11-13 Practical Asymmetric Synthesis of Sitagliptin Phosphate Monohydrate Gao, Haoling Yu, Jiangang Ge, Chengsheng Jiang, Qun Molecules Article Optically pure sitagliptin phosphate monohydrate is efficiently and practically synthesized through a chiral hemiacetal as the key intermediate in 54% overall yield starting from (E)-4-(2,4,5-trifluorophenyl)but-2-enal and N-boc-protected hydroxylamine. The chiral hemiacetal fragment is constructed by a tandem aza-Michael/hemiacetal reaction catalyzed by an organocatalyst and the influence of acidity of Brønsted acid on tandem aza-Michael/hemiacetal reaction is researched in detail. MDPI 2018-06-13 /pmc/articles/PMC6099835/ /pubmed/29899310 http://dx.doi.org/10.3390/molecules23061440 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Gao, Haoling
Yu, Jiangang
Ge, Chengsheng
Jiang, Qun
Practical Asymmetric Synthesis of Sitagliptin Phosphate Monohydrate
title Practical Asymmetric Synthesis of Sitagliptin Phosphate Monohydrate
title_full Practical Asymmetric Synthesis of Sitagliptin Phosphate Monohydrate
title_fullStr Practical Asymmetric Synthesis of Sitagliptin Phosphate Monohydrate
title_full_unstemmed Practical Asymmetric Synthesis of Sitagliptin Phosphate Monohydrate
title_short Practical Asymmetric Synthesis of Sitagliptin Phosphate Monohydrate
title_sort practical asymmetric synthesis of sitagliptin phosphate monohydrate
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6099835/
https://www.ncbi.nlm.nih.gov/pubmed/29899310
http://dx.doi.org/10.3390/molecules23061440
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AT jiangqun practicalasymmetricsynthesisofsitagliptinphosphatemonohydrate

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