Selectively fluorinated citronellol analogues support a hydrogen bonding donor interaction with the human OR1A1 olfactory receptor

Mengfan He; Weihong Liu; Chen Zhang; Yingjian Liu; Hanyi Zhuang; David O'Hagan

doi:10.1021/acs.orglett.2c01635

Selectively fluorinated citronellol analogues support a hydrogen bonding donor interaction with the human OR1A1 olfactory receptor

Mengfan He, Weihong Liu, Chen Zhang, Yingjian Liu, Hanyi Zhuang^*, David O'Hagan^*

^*Corresponding author for this work

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

Abstract

C-2 fluorinated and methylated stereoisomers of the fragrance citronellol 1 and its oxalate esters were prepared from (R)-pulegone 11 and explored as agonists of the human olfactory receptor OR1A1 and assayed also against site-specific mutants. There were clear isomer preferences and C-2 difluorination as in 18 led to the most active compound suggesting an important hydrogen bond donor role for citronellol 1. C-2 methylation and the corresponding oxalate ester analogues were less active.

Original language	English
Number of pages	6
Journal	Organic Letters
Volume	Articles ASAP
Early online date	10 Jun 2022
DOIs	https://doi.org/10.1021/acs.orglett.2c01635
Publication status	E-pub ahead of print - 10 Jun 2022

Access to Document

10.1021/acs.orglett.2c01635Licence: CC BY

He_2022_OL_Selectively-fluorinated-citronellol-analogues_CC
Copyright © 2022 The Authors. Published by American Chemical Society. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Final published version, 1.11 MBLicence: CC BY

Cite this

@article{93c5869f7cac40bc87a20f6ce98acb56,

title = "Selectively fluorinated citronellol analogues support a hydrogen bonding donor interaction with the human OR1A1 olfactory receptor",

abstract = "C-2 fluorinated and methylated stereoisomers of the fragrance citronellol 1 and its oxalate esters were prepared from (R)-pulegone 11 and explored as agonists of the human olfactory receptor OR1A1 and assayed also against site-specific mutants. There were clear isomer preferences and C-2 difluorination as in 18 led to the most active compound suggesting an important hydrogen bond donor role for citronellol 1. C-2 methylation and the corresponding oxalate ester analogues were less active.",

author = "Mengfan He and Weihong Liu and Chen Zhang and Yingjian Liu and Hanyi Zhuang and David O'Hagan",

note = "Authors thank the Chinese Scholarship Council for funding a Studentship (No. 202008060063) at the University of St. Andrews, U.K.",

year = "2022",

month = jun,

day = "10",

doi = "10.1021/acs.orglett.2c01635",

language = "English",

volume = "Articles ASAP",

journal = "Organic Letters",

issn = "1523-7060",

publisher = "American Chemical Society (ACS)",

}

TY - JOUR

T1 - Selectively fluorinated citronellol analogues support a hydrogen bonding donor interaction with the human OR1A1 olfactory receptor

AU - He, Mengfan

AU - Liu, Weihong

AU - Zhang, Chen

AU - Liu, Yingjian

AU - Zhuang, Hanyi

AU - O'Hagan, David

N1 - Authors thank the Chinese Scholarship Council for funding a Studentship (No. 202008060063) at the University of St. Andrews, U.K.

PY - 2022/6/10

Y1 - 2022/6/10

N2 - C-2 fluorinated and methylated stereoisomers of the fragrance citronellol 1 and its oxalate esters were prepared from (R)-pulegone 11 and explored as agonists of the human olfactory receptor OR1A1 and assayed also against site-specific mutants. There were clear isomer preferences and C-2 difluorination as in 18 led to the most active compound suggesting an important hydrogen bond donor role for citronellol 1. C-2 methylation and the corresponding oxalate ester analogues were less active.

AB - C-2 fluorinated and methylated stereoisomers of the fragrance citronellol 1 and its oxalate esters were prepared from (R)-pulegone 11 and explored as agonists of the human olfactory receptor OR1A1 and assayed also against site-specific mutants. There were clear isomer preferences and C-2 difluorination as in 18 led to the most active compound suggesting an important hydrogen bond donor role for citronellol 1. C-2 methylation and the corresponding oxalate ester analogues were less active.

U2 - 10.1021/acs.orglett.2c01635

DO - 10.1021/acs.orglett.2c01635

M3 - Article

SN - 1523-7060

VL - Articles ASAP

JO - Organic Letters

JF - Organic Letters

ER -

Selectively fluorinated citronellol analogues support a hydrogen bonding donor interaction with the human OR1A1 olfactory receptor

Abstract

Access to Document

Fingerprint

Cite this