Multi-Catalytic Route for the Synthesis of (<i>S</i>)-Tembamide

Enantiopure β-amino alcohols constitute one of the most significant building blocks for the synthesis of active pharmaceutical ingredients. Despite the availability of a range of chiral β-amino alcohols from a chiral pool, there is a growing demand for new enantioselective syntheti...

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Main Authors:	Laura Leemans, Marc D. Walter, Frank Hollmann, Anett Schallmey, Luuk M. van Langen
Format:	Article
Language:	English
Published:	MDPI AG 2019-09-01
Series:	Catalysts
Subjects:	enantioselectivity chemoenzymatic cascade hydroxynitrile lyase lipase raney ni hydrocyanation transesterification catalytic hydrogenation nitrile reduction tembamide
Online Access:	https://www.mdpi.com/2073-4344/9/10/822

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spelling	doaj-98a4579bb5c74379981f4594aa98e1712020-11-25T01:42:23ZengMDPI AGCatalysts2073-43442019-09-0191082210.3390/catal9100822catal9100822Multi-Catalytic Route for the Synthesis of (<i>S</i>)-TembamideLaura Leemans0Marc D. Walter1Frank Hollmann2Anett Schallmey3Luuk M. van Langen4Institute for Biochemistry, Biotechnology and Bioinformatics, Technische Universität Braunschweig, Spielmannstr. 7, 38106 Braunschweig, GermanyInstitute for Inorganic and Analytical Chemistry, Technische Universität Braunschweig, Hagenring 30, 38106 Braunschweig, GermanyDepartment of Biotechnology, Delft University of Technology, Van der Maasweg 9, 2629 HZ Delft, The NetherlandsInstitute for Biochemistry, Biotechnology and Bioinformatics, Technische Universität Braunschweig, Spielmannstr. 7, 38106 Braunschweig, GermanyViazym B.V., Molengraaffsingel 10, 2629, JD Delft, The NetherlandsEnantiopure β-amino alcohols constitute one of the most significant building blocks for the synthesis of active pharmaceutical ingredients. Despite the availability of a range of chiral β-amino alcohols from a chiral pool, there is a growing demand for new enantioselective synthetic routes to vicinal amino alcohols and their derivatives. In the present study, an asymmetric 2-step catalytic route that converts 4-anisaldehyde into a β-amino alcohol derivative, (<i>S</i>)-tembamide, with excellent enantiopurity (98% enantiomeric excess) has been developed. The recently published initial step consists in a concurrent biocatalytic cascade for the synthesis of (<i>S</i>)-4-methoxymandelonitrile benzoate. The <i>O</i>-benzoyl cyanohydrin is then converted to (<i>S</i>)-tembamide in a hydrogenation reaction catalyzed by Raney Ni. To achieve hydrogenation of the nitrile moiety with highest chemoselectivity and enantioretention, various parameters such as nature of the catalyst, reaction temperature and hydrogen pressure were studied. The reported strategy might be transferrable to the synthesis of other <i>N</i>-acyl-β-amino alcohols.https://www.mdpi.com/2073-4344/9/10/822enantioselectivitychemoenzymatic cascadehydroxynitrile lyaselipaseraney nihydrocyanationtransesterificationcatalytic hydrogenationnitrile reductiontembamide
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Laura Leemans Marc D. Walter Frank Hollmann Anett Schallmey Luuk M. van Langen
spellingShingle	Laura Leemans Marc D. Walter Frank Hollmann Anett Schallmey Luuk M. van Langen Multi-Catalytic Route for the Synthesis of (<i>S</i>)-Tembamide Catalysts enantioselectivity chemoenzymatic cascade hydroxynitrile lyase lipase raney ni hydrocyanation transesterification catalytic hydrogenation nitrile reduction tembamide
author_facet	Laura Leemans Marc D. Walter Frank Hollmann Anett Schallmey Luuk M. van Langen
author_sort	Laura Leemans
title	Multi-Catalytic Route for the Synthesis of (<i>S</i>)-Tembamide
title_short	Multi-Catalytic Route for the Synthesis of (<i>S</i>)-Tembamide
title_full	Multi-Catalytic Route for the Synthesis of (<i>S</i>)-Tembamide
title_fullStr	Multi-Catalytic Route for the Synthesis of (<i>S</i>)-Tembamide
title_full_unstemmed	Multi-Catalytic Route for the Synthesis of (<i>S</i>)-Tembamide
title_sort	multi-catalytic route for the synthesis of (<i>s</i>)-tembamide
publisher	MDPI AG
series	Catalysts
issn	2073-4344
publishDate	2019-09-01
description	Enantiopure β-amino alcohols constitute one of the most significant building blocks for the synthesis of active pharmaceutical ingredients. Despite the availability of a range of chiral β-amino alcohols from a chiral pool, there is a growing demand for new enantioselective synthetic routes to vicinal amino alcohols and their derivatives. In the present study, an asymmetric 2-step catalytic route that converts 4-anisaldehyde into a β-amino alcohol derivative, (<i>S</i>)-tembamide, with excellent enantiopurity (98% enantiomeric excess) has been developed. The recently published initial step consists in a concurrent biocatalytic cascade for the synthesis of (<i>S</i>)-4-methoxymandelonitrile benzoate. The <i>O</i>-benzoyl cyanohydrin is then converted to (<i>S</i>)-tembamide in a hydrogenation reaction catalyzed by Raney Ni. To achieve hydrogenation of the nitrile moiety with highest chemoselectivity and enantioretention, various parameters such as nature of the catalyst, reaction temperature and hydrogen pressure were studied. The reported strategy might be transferrable to the synthesis of other <i>N</i>-acyl-β-amino alcohols.
topic	enantioselectivity chemoenzymatic cascade hydroxynitrile lyase lipase raney ni hydrocyanation transesterification catalytic hydrogenation nitrile reduction tembamide
url	https://www.mdpi.com/2073-4344/9/10/822
work_keys_str_mv	AT lauraleemans multicatalyticrouteforthesynthesisofisitembamide AT marcdwalter multicatalyticrouteforthesynthesisofisitembamide AT frankhollmann multicatalyticrouteforthesynthesisofisitembamide AT anettschallmey multicatalyticrouteforthesynthesisofisitembamide AT luukmvanlangen multicatalyticrouteforthesynthesisofisitembamide
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Multi-Catalytic Route for the Synthesis of (<i>S</i>)-Tembamide

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