Design and synthesis of boron containing monosaccharides by the hydroboration of d-glucal for use in boron neutron capture therapy (BNCT)

• Published in: Bioorganic & medicinal chemistry Vol. 26; no. 22; pp. 5922 - 5933
• Main Authors: Itoh, Taiki, Tamura, Kei, Ueda, Hiroki, Tanaka, Tomohiro, Sato, Kyouhei, Kuroda, Reiko, Aoki, Shin
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 01.12.2018; Elsevier
• Subjects: A549 Cells; Biochemistry & Molecular Biology; Boron - chemistry; Boron - pharmacology; Boron Neutron Capture Therapy; Boron neutron capture therapy (BNCT); Boronic acid esters; Cell Survival - drug effects; Chemistry; Chemistry, Medicinal; Chemistry, Organic; Deoxyglucose - analogs & derivatives; Deoxyglucose - chemistry; Deoxyglucose - pharmacology; Dose-Response Relationship, Drug; Drug Design; Glucose transporter; Glycosides; HeLa Cells; Humans; Hydroboration; Life Sciences & Biomedicine; Molecular Structure; Monosaccharides - chemical synthesis; Monosaccharides - chemistry; Monosaccharides - pharmacology; Pharmacology & Pharmacy; Physical Sciences; Science & Technology; Structure-Activity Relationship; Glucose transporter; Glycosides; Boronic acid esters; Hydroboration; Boron neutron capture therapy (BNCT); ORTHO-CARBORANYL GLYCOSIDES; POTENTIAL USE; CRYSTAL-STRUCTURE; GLUCOSE TRANSPORTERS; MALIGNANT-MELANOMA; IN-VITRO; SELECTIVE DELIVERY; CANCER METABOLISM; DIRECT EPOXIDATION; PROTECTING GROUPS
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2018.10.041

[Display omitted] Boron neutron capture therapy (BNCT) is one of the radiotherapies that involves the use of boron-containing compounds for the treatment of cancer. Boron-10 (10B) containing compounds that can accumulate in tumor tissue are expected to be suitable agents for BNCT. We report herein on the design and synthesis of some new BNCT agents based on a d-glucose scaffold, since glycoconjugation has been recognized as a useful strategy for the specific targeting of tumors. To introduce a boryl group into a d-glucose scaffold, we focused on the hydroboration of d-glucal derivatives, which have a double bond between the C1 and C2 positions. It was hypothesized that a C–B bond could be introduced at the C2 position of d-glucose by the hydroboration of d-glucal derivatives and that the products could be stabilized by conversion to the corresponding boronic acid ester. To test this hypothesis, we prepared some 2-boryl-1,2-dideoxy-d-glucose derivatives as boron carriers and evaluated their cytotoxicity and cellular uptake activity to cancer cells, especially under hypoxic conditions.