Chemoenzymatic Synthesis of Chiral 1-Benzyl-5-(hydroxymethyl)-2-piperidone Enabled by Lipase AK-Mediated Desymmetrization of Prochiral 1,3-Diol and Its Diacetate

Duc Thinh Khong; Varsha Siri Pamarthy; Timothy Gallagher; Zaher M.A. Judeh

doi:10.1002/ejoc.201600262

Chemoenzymatic Synthesis of Chiral 1-Benzyl-5-(hydroxymethyl)-2-piperidone Enabled by Lipase AK-Mediated Desymmetrization of Prochiral 1,3-Diol and Its Diacetate

Duc Thinh Khong, Varsha Siri Pamarthy, Timothy Gallagher^*, Zaher M.A. Judeh

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

10 Citations (Scopus)

Abstract

The synthesis of (R)-1-benzyl-5-(hydroxymethyl)-2-piperidone (1) from key synthon monoacetate (R)-3 has been accomplished conveniently in 6 steps with 93 % ee and in 44 % overall yield. The key step involved lipase AK-mediated desymmetrization of diol 4 to produce monoacetate (R)-3 in 93 % ee and 93 % yield. Additionally, lipase AK-mediated desymmetrization of diacetate 5 readily provided access to monoacetate (S)-3 in 93 % ee and 54 % yield.

Original language	English
Pages (from-to)	3084-3089
Number of pages	6
Journal	European Journal of Organic Chemistry
Volume	2016
Issue number	18
DOIs	https://doi.org/10.1002/ejoc.201600262
Publication status	Published - Jun 2016
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

ASJC Scopus Subject Areas

Physical and Theoretical Chemistry
Organic Chemistry

Keywords

Acylation
Enantioselectivity
Enzyme catalysis
Nitrogen heterocycles

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10.1002/ejoc.201600262

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title = "Chemoenzymatic Synthesis of Chiral 1-Benzyl-5-(hydroxymethyl)-2-piperidone Enabled by Lipase AK-Mediated Desymmetrization of Prochiral 1,3-Diol and Its Diacetate",

abstract = "The synthesis of (R)-1-benzyl-5-(hydroxymethyl)-2-piperidone (1) from key synthon monoacetate (R)-3 has been accomplished conveniently in 6 steps with 93 % ee and in 44 % overall yield. The key step involved lipase AK-mediated desymmetrization of diol 4 to produce monoacetate (R)-3 in 93 % ee and 93 % yield. Additionally, lipase AK-mediated desymmetrization of diacetate 5 readily provided access to monoacetate (S)-3 in 93 % ee and 54 % yield.",

keywords = "Acylation, Enantioselectivity, Enzyme catalysis, Nitrogen heterocycles",

author = "Khong, {Duc Thinh} and Pamarthy, {Varsha Siri} and Timothy Gallagher and Judeh, {Zaher M.A.}",

note = "Publisher Copyright: {\textcopyright} 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim",

year = "2016",

month = jun,

doi = "10.1002/ejoc.201600262",

language = "English",

volume = "2016",

pages = "3084--3089",

journal = "European Journal of Organic Chemistry",

issn = "1434-193X",

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}

Chemoenzymatic Synthesis of Chiral 1-Benzyl-5-(hydroxymethyl)-2-piperidone Enabled by Lipase AK-Mediated Desymmetrization of Prochiral 1,3-Diol and Its Diacetate. / Khong, Duc Thinh; Pamarthy, Varsha Siri; Gallagher, Timothy et al.
In: European Journal of Organic Chemistry, Vol. 2016, No. 18, 06.2016, p. 3084-3089.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Chemoenzymatic Synthesis of Chiral 1-Benzyl-5-(hydroxymethyl)-2-piperidone Enabled by Lipase AK-Mediated Desymmetrization of Prochiral 1,3-Diol and Its Diacetate

AU - Khong, Duc Thinh

AU - Pamarthy, Varsha Siri

AU - Gallagher, Timothy

AU - Judeh, Zaher M.A.

PY - 2016/6

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N2 - The synthesis of (R)-1-benzyl-5-(hydroxymethyl)-2-piperidone (1) from key synthon monoacetate (R)-3 has been accomplished conveniently in 6 steps with 93 % ee and in 44 % overall yield. The key step involved lipase AK-mediated desymmetrization of diol 4 to produce monoacetate (R)-3 in 93 % ee and 93 % yield. Additionally, lipase AK-mediated desymmetrization of diacetate 5 readily provided access to monoacetate (S)-3 in 93 % ee and 54 % yield.

AB - The synthesis of (R)-1-benzyl-5-(hydroxymethyl)-2-piperidone (1) from key synthon monoacetate (R)-3 has been accomplished conveniently in 6 steps with 93 % ee and in 44 % overall yield. The key step involved lipase AK-mediated desymmetrization of diol 4 to produce monoacetate (R)-3 in 93 % ee and 93 % yield. Additionally, lipase AK-mediated desymmetrization of diacetate 5 readily provided access to monoacetate (S)-3 in 93 % ee and 54 % yield.

KW - Acylation

KW - Enantioselectivity

KW - Enzyme catalysis

KW - Nitrogen heterocycles

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DO - 10.1002/ejoc.201600262

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VL - 2016

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JO - European Journal of Organic Chemistry

JF - European Journal of Organic Chemistry

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ER -

Chemoenzymatic Synthesis of Chiral 1-Benzyl-5-(hydroxymethyl)-2-piperidone Enabled by Lipase AK-Mediated Desymmetrization of Prochiral 1,3-Diol and Its Diacetate

Abstract

Bibliographical note

ASJC Scopus Subject Areas

Keywords

Access to Document

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