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

Research output: Contribution to journal › Article (Academic Journal) › peer-review

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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
Early online date	13 Jun 2016
DOIs	https://doi.org/10.1002/ejoc.201600262
Publication status	Published - Jun 2016

Keywords

Enzyme catalysis
Enantioselectivity
Acylation
Nitrogen heterocycles

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@article{143cc189fd3d49e09c1274d840153b6f,

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

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

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",

publisher = "Wiley-VCH Verlag",

number = "18",

}

Chemoenzymatic Synthesis of Chiral 1-Benzyl-5-(hydroxymethyl)- 2-piperidone Enabled by Lipase AK-Mediated Desymmetrization of Prochiral 1,3-Diol and Its Diacetate. / Thinh Khong, Duc; Siri Pamarthy, Varsha; 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 (Academic Journal) › 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 - Thinh Khong, Duc

AU - Siri Pamarthy, Varsha

AU - Gallagher, Timothy

AU - Judeh, Zaher M A

PY - 2016/6

Y1 - 2016/6

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 - Enzyme catalysis

KW - Enantioselectivity

KW - Acylation

KW - Nitrogen heterocycles

U2 - 10.1002/ejoc.201600262

DO - 10.1002/ejoc.201600262

M3 - Article (Academic Journal)

SN - 1434-193X

VL - 2016

SP - 3084

EP - 3089

JO - European Journal of Organic Chemistry

JF - European Journal of Organic Chemistry

IS - 18

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

Keywords

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