Copper-Mediated Radiosynthesis of [F-18]Rucaparib

Zijun Chen; Gianluca Destro; Florian Guibbal; Chung Ying Chan; Bart Cornelissen; Véronique Gouverneur

doi:10.1021/acs.orglett.1c02770

Copper-Mediated Radiosynthesis of [F-18]Rucaparib

Zijun Chen
, Gianluca Destro
, Florian Guibbal
, Chung Ying Chan
, Bart Cornelissen
, Véronique Gouverneur^*

^*Corresponding author for this work

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

33 Citations (Scopus)

Abstract

The poly(ADP-ribose) polymerase (PARP) inhibitor rucaparib is used in the clinic to treat BRCA-mutated cancers. Herein, we report two strategies to access the F-18-isotopologue of rucaparib by applying a copper-mediated nucleophilic F-18-fluorodeboronation. The most successful approach features an aldehydic boronic ester precursor that is subjected to reductive amination post-F-18-labeling and affords [F-18]rucaparib with an activity yield of 11% +/- 3% (n = 3) and a molar activity (Am) up to 30 GBq/mu mol. Preliminary in vitro studies are presented.

Original language	English
Pages (from-to)	7290-7294
Number of pages	5
Journal	Organic letters
Volume	23
Issue number	18
DOIs	https://doi.org/10.1021/acs.orglett.1c02770
Publication status	Published - 17-Sept-2021
Externally published	Yes

Keywords

PARP-1 EXPRESSION
INHIBITORS
PROVIDES
F-18
F-18-FLUORINATION

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@article{f190826701c44bc184bd391e7d5adb41,

title = "Copper-Mediated Radiosynthesis of [F-18]Rucaparib",

abstract = "The poly(ADP-ribose) polymerase (PARP) inhibitor rucaparib is used in the clinic to treat BRCA-mutated cancers. Herein, we report two strategies to access the F-18-isotopologue of rucaparib by applying a copper-mediated nucleophilic F-18-fluorodeboronation. The most successful approach features an aldehydic boronic ester precursor that is subjected to reductive amination post-F-18-labeling and affords [F-18]rucaparib with an activity yield of 11\% +/- 3\% (n = 3) and a molar activity (Am) up to 30 GBq/mu mol. Preliminary in vitro studies are presented.",

keywords = "PARP-1 EXPRESSION, INHIBITORS, PROVIDES, F-18, F-18-FLUORINATION",

author = "Zijun Chen and Gianluca Destro and Florian Guibbal and Chan, \{Chung Ying\} and Bart Cornelissen and V{\'e}ronique Gouverneur",

note = "Funding Information: We acknowledge financial support from Cancer Research UK through the Oxford Institute for Radiation Oncology, Medical Research Council (MRC) (MR/R01695X/1, G.D. and F.G.) and Pancreatic Cancer UK (PCUK H3R00510, C.Y.C). Publisher Copyright: {\textcopyright} 2021 American Chemical Society.",

year = "2021",

month = sep,

day = "17",

doi = "10.1021/acs.orglett.1c02770",

language = "English",

volume = "23",

pages = "7290--7294",

journal = "Organic letters",

issn = "1523-7060",

publisher = "AMER CHEMICAL SOC INC",

number = "18",

}

TY - JOUR

T1 - Copper-Mediated Radiosynthesis of [F-18]Rucaparib

AU - Chen, Zijun

AU - Destro, Gianluca

AU - Guibbal, Florian

AU - Chan, Chung Ying

AU - Cornelissen, Bart

AU - Gouverneur, Véronique

N1 - Funding Information: We acknowledge financial support from Cancer Research UK through the Oxford Institute for Radiation Oncology, Medical Research Council (MRC) (MR/R01695X/1, G.D. and F.G.) and Pancreatic Cancer UK (PCUK H3R00510, C.Y.C). Publisher Copyright: © 2021 American Chemical Society.

PY - 2021/9/17

Y1 - 2021/9/17

N2 - The poly(ADP-ribose) polymerase (PARP) inhibitor rucaparib is used in the clinic to treat BRCA-mutated cancers. Herein, we report two strategies to access the F-18-isotopologue of rucaparib by applying a copper-mediated nucleophilic F-18-fluorodeboronation. The most successful approach features an aldehydic boronic ester precursor that is subjected to reductive amination post-F-18-labeling and affords [F-18]rucaparib with an activity yield of 11% +/- 3% (n = 3) and a molar activity (Am) up to 30 GBq/mu mol. Preliminary in vitro studies are presented.

AB - The poly(ADP-ribose) polymerase (PARP) inhibitor rucaparib is used in the clinic to treat BRCA-mutated cancers. Herein, we report two strategies to access the F-18-isotopologue of rucaparib by applying a copper-mediated nucleophilic F-18-fluorodeboronation. The most successful approach features an aldehydic boronic ester precursor that is subjected to reductive amination post-F-18-labeling and affords [F-18]rucaparib with an activity yield of 11% +/- 3% (n = 3) and a molar activity (Am) up to 30 GBq/mu mol. Preliminary in vitro studies are presented.

KW - PARP-1 EXPRESSION

KW - INHIBITORS

KW - PROVIDES

KW - F-18

KW - F-18-FLUORINATION

UR - https://www.scopus.com/pages/publications/85114689136

U2 - 10.1021/acs.orglett.1c02770

DO - 10.1021/acs.orglett.1c02770

M3 - Article

C2 - 34459606

AN - SCOPUS:85114689136

SN - 1523-7060

VL - 23

SP - 7290

EP - 7294

JO - Organic letters

JF - Organic letters

IS - 18

ER -

Copper-Mediated Radiosynthesis of [F-18]Rucaparib

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Keywords

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