Vicinal difluorination as a C=C surrogate: an analog of piperine with enhanced solubility, photostability, and acetylcholinesterase inhibitory activity

Yuvixza Lizarme-Salas; Alexandra Daryl Ariawan; Ranjala Ratnayake; Hendrik Luesch; Angela Finch; Luke Hunter

doi:10.3762/BJOC.16.216

Vicinal difluorination as a C=C surrogate: an analog of piperine with enhanced solubility, photostability, and acetylcholinesterase inhibitory activity

Yuvixza Lizarme-Salas, Alexandra Daryl Ariawan, Ranjala Ratnayake, Hendrik Luesch, Angela Finch, Luke Hunter^*

^*Corresponding author for this work

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

9 Citations (Scopus)

33 Downloads (Pure)

Abstract

Piperine, a natural product derived from peppercorns, has a variety of biological activities that make it an attractive lead compound for medicinal chemistry. However, piperine has some problematic physicochemical properties including poor aqueous solubility and a susceptibility to UV-induced degradation. In this work, we designed an analog of piperine in which the central conjugated hydrocarbon chain is replaced with a vicinal difluoroalkane moiety. We show that this fluorinated analog of piperine has superior physicochemical properties, and it also has higher potency and selectivity towards one particular drug target, acetylcholinesterase. This work highlights the potential usefulness of the threo-difluoroalkane motif as a surrogate for E-alkenes in medicinal chemistry.

Original language	English
Pages (from-to)	2663-2670
Number of pages	8
Journal	Beilstein Journal of Organic Chemistry
Volume	16
DOIs	https://doi.org/10.3762/BJOC.16.216
Publication status	Published - 28 Oct 2020
Externally published	Yes

Bibliographical note

Copyright the Author(s) 2020. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

Keywords

Alzheimer's disease
Bioisostere
Conformational analysis
Gauche effect
Stereoselective synthesis

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10.3762/BJOC.16.216Licence: CC BY

Publisher version (open access)Final published version, 989 KBLicence: CC BY

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title = "Vicinal difluorination as a C=C surrogate: an analog of piperine with enhanced solubility, photostability, and acetylcholinesterase inhibitory activity",

abstract = "Piperine, a natural product derived from peppercorns, has a variety of biological activities that make it an attractive lead compound for medicinal chemistry. However, piperine has some problematic physicochemical properties including poor aqueous solubility and a susceptibility to UV-induced degradation. In this work, we designed an analog of piperine in which the central conjugated hydrocarbon chain is replaced with a vicinal difluoroalkane moiety. We show that this fluorinated analog of piperine has superior physicochemical properties, and it also has higher potency and selectivity towards one particular drug target, acetylcholinesterase. This work highlights the potential usefulness of the threo-difluoroalkane motif as a surrogate for E-alkenes in medicinal chemistry.",

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author = "Yuvixza Lizarme-Salas and Ariawan, {Alexandra Daryl} and Ranjala Ratnayake and Hendrik Luesch and Angela Finch and Luke Hunter",

note = "Copyright the Author(s) 2020. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.",

year = "2020",

month = oct,

day = "28",

doi = "10.3762/BJOC.16.216",

language = "English",

volume = "16",

pages = "2663--2670",

journal = "Beilstein Journal of Organic Chemistry",

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Vicinal difluorination as a C=C surrogate: an analog of piperine with enhanced solubility, photostability, and acetylcholinesterase inhibitory activity. / Lizarme-Salas, Yuvixza; Ariawan, Alexandra Daryl; Ratnayake, Ranjala et al.
In: Beilstein Journal of Organic Chemistry, Vol. 16, 28.10.2020, p. 2663-2670.

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

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AU - Lizarme-Salas, Yuvixza

AU - Ariawan, Alexandra Daryl

AU - Ratnayake, Ranjala

AU - Luesch, Hendrik

AU - Finch, Angela

AU - Hunter, Luke

N1 - Copyright the Author(s) 2020. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

PY - 2020/10/28

Y1 - 2020/10/28

N2 - Piperine, a natural product derived from peppercorns, has a variety of biological activities that make it an attractive lead compound for medicinal chemistry. However, piperine has some problematic physicochemical properties including poor aqueous solubility and a susceptibility to UV-induced degradation. In this work, we designed an analog of piperine in which the central conjugated hydrocarbon chain is replaced with a vicinal difluoroalkane moiety. We show that this fluorinated analog of piperine has superior physicochemical properties, and it also has higher potency and selectivity towards one particular drug target, acetylcholinesterase. This work highlights the potential usefulness of the threo-difluoroalkane motif as a surrogate for E-alkenes in medicinal chemistry.

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KW - Bioisostere

KW - Conformational analysis

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ER -

Vicinal difluorination as a C=C surrogate: an analog of piperine with enhanced solubility, photostability, and acetylcholinesterase inhibitory activity

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