Synthesis of Unsymmetrical Difluoromethylene Bisphosphonates

Jianyun Guo; Pascal Balić; Vladimir S. Borodkin; Dmitri V. Filippov; Jeroen D. C. Codée

doi:10.1021/acs.orglett.3c04211

Synthesis of Unsymmetrical Difluoromethylene Bisphosphonates

Jianyun Guo, Pascal Balić, Vladimir S. Borodkin, Dmitri V. Filippov (Lead / Corresponding author), Jeroen D. C. Codée (Lead / Corresponding author)

Molecular Cell and Developmental Biology

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Abstract

We demonstrate the use of the symmetrical diethyl(dimethyl)difluoromethylene bisphosphonate reagent for the synthesis of terminal and unsymmetrical difluoromethylene bisphosphonates, close analogues of biologically important molecules. The difference in reactivity of the methyl and ethyl groups in the symmetrical diethyl(dimthyl)difluoromethylene bisphosphonate is exploited in a stepwise demethylation-condensation sequence to functionalize either side of the reagent to allow the generation of a series of close bioisosteres of natural pyrophosphate molecules, including ADPr, CDP-glycerol and CDP-ribitol.

Original language	English
Pages (from-to)	739-744
Number of pages	6
Journal	Organic Letters
Volume	26
Issue number	3
Early online date	12 Jan 2024
DOIs	https://doi.org/10.1021/acs.orglett.3c04211
Publication status	Published - 26 Jan 2024

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title = "Synthesis of Unsymmetrical Difluoromethylene Bisphosphonates",

abstract = "We demonstrate the use of the symmetrical diethyl(dimethyl)difluoromethylene bisphosphonate reagent for the synthesis of terminal and unsymmetrical difluoromethylene bisphosphonates, close analogues of biologically important molecules. The difference in reactivity of the methyl and ethyl groups in the symmetrical diethyl(dimthyl)difluoromethylene bisphosphonate is exploited in a stepwise demethylation-condensation sequence to functionalize either side of the reagent to allow the generation of a series of close bioisosteres of natural pyrophosphate molecules, including ADPr, CDP-glycerol and CDP-ribitol.",

author = "Jianyun Guo and Pascal Bali{\'c} and Borodkin, {Vladimir S.} and Filippov, {Dmitri V.} and Cod{\'e}e, {Jeroen D. C.}",

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doi = "10.1021/acs.orglett.3c04211",

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T1 - Synthesis of Unsymmetrical Difluoromethylene Bisphosphonates

AU - Guo, Jianyun

AU - Balić, Pascal

AU - Borodkin, Vladimir S.

AU - Filippov, Dmitri V.

AU - Codée, Jeroen D. C.

PY - 2024/1/26

Y1 - 2024/1/26

N2 - We demonstrate the use of the symmetrical diethyl(dimethyl)difluoromethylene bisphosphonate reagent for the synthesis of terminal and unsymmetrical difluoromethylene bisphosphonates, close analogues of biologically important molecules. The difference in reactivity of the methyl and ethyl groups in the symmetrical diethyl(dimthyl)difluoromethylene bisphosphonate is exploited in a stepwise demethylation-condensation sequence to functionalize either side of the reagent to allow the generation of a series of close bioisosteres of natural pyrophosphate molecules, including ADPr, CDP-glycerol and CDP-ribitol.

AB - We demonstrate the use of the symmetrical diethyl(dimethyl)difluoromethylene bisphosphonate reagent for the synthesis of terminal and unsymmetrical difluoromethylene bisphosphonates, close analogues of biologically important molecules. The difference in reactivity of the methyl and ethyl groups in the symmetrical diethyl(dimthyl)difluoromethylene bisphosphonate is exploited in a stepwise demethylation-condensation sequence to functionalize either side of the reagent to allow the generation of a series of close bioisosteres of natural pyrophosphate molecules, including ADPr, CDP-glycerol and CDP-ribitol.

U2 - 10.1021/acs.orglett.3c04211

DO - 10.1021/acs.orglett.3c04211

M3 - Article

C2 - 38215221

SN - 1523-7060

VL - 26

SP - 739

EP - 744

JO - Organic Letters

JF - Organic Letters

IS - 3

ER -

Synthesis of Unsymmetrical Difluoromethylene Bisphosphonates

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