Synthesis of (11)C-labeled retinoic acid, [(11)C]ATRA, via an alkenylboron precursor by Pd(0)-mediated rapid C-[(11)C]methylation

Masaaki Suzuki; Misato Takashima-Hirano; Hideki Ishii; Chika Watanabe; Kengo Sumi; Hiroko Koyama; Hisashi Doi

doi:10.1016/j.bmcl.2014.05.041

Synthesis of (11)C-labeled retinoic acid, [(11)C]ATRA, via an alkenylboron precursor by Pd(0)-mediated rapid C-[(11)C]methylation

Bioorg Med Chem Lett. 2014 Aug 1;24(15):3622-5. doi: 10.1016/j.bmcl.2014.05.041. Epub 2014 Jun 2.

Authors

Masaaki Suzuki¹, Misato Takashima-Hirano², Hideki Ishii³, Chika Watanabe⁴, Kengo Sumi⁴, Hiroko Koyama⁴, Hisashi Doi⁵

Affiliations

¹ Center for Development of Advanced Medicine for Dementia, National Center for Geriatrics and Gerontology Center, 35, Gengo Morioka-cho, Obu-shi, Aichi 474-8511, Japan; RIKEN Center for Molecular Imaging Science (CMIS), 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan. Electronic address: suzukims@ncgg.go.jp.
² RIKEN Center for Molecular Imaging Science (CMIS), 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.
³ Molecular Imaging Center, National Institute of Radiological Science (NIRS), 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan.
⁴ Division of Regeneration and Advanced Medical Science, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1184, Japan.
⁵ RIKEN Center for Molecular Imaging Science (CMIS), 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan; RIKEN Center for Life Science Technologies (CLST), 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.

PMID: 24930828
DOI: 10.1016/j.bmcl.2014.05.041

Abstract

Retinoids are a class of chemical compounds which include both natural dietary vitamin A (retinol) metabolites and active synthetic analogs. Both experimental and clinical studies have revealed that retinoids regulate a wide variety of essential biological processes. In this study, we synthesized (11)C-labeled all-trans-retinoic acid (ATRA), the most potent biologically active metabolite of retinol and used in the treatment of acute promyelocytic leukemia. The synthesis of (11)C-labeled ATRA was accomplished by a combination of rapid Pd(0)-mediated C-[(11)C]methylation of the corresponding pinacol borate precursor prepared by 8 steps and hydrolysis. [(11)C]ATRA will prove useful as a PET imaging agent, particularly for elucidating the improved therapeutic activity of ATRA (natural retinoid) for acute promyelocytic leukemia by comparing with the corresponding PET probe [(11)C]Tamibarotene (artificial retinoid).

Keywords: (11)C labeling; PET; Retinoids.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alkenes / chemistry
Antineoplastic Agents / chemical synthesis*
Antineoplastic Agents / therapeutic use
Boron Compounds / chemistry*
Carbon Isotopes
Catalysis
Contrast Media
Humans
Leukemia, Promyelocytic, Acute / drug therapy*
Methylation
Palladium / chemistry*
Positron-Emission Tomography
Tretinoin / chemical synthesis*
Tretinoin / therapeutic use

Substances

Alkenes
Antineoplastic Agents
Boron Compounds
Carbon Isotopes
Contrast Media
Tretinoin
Palladium