Bicyclic Systems With Bridgehead (Ring Junction) Boron Atoms

Garget, Taylor A.; Houston, Todd Ashley; Kiefel, Milton J.; Simone, Michela I.

doi:10.1016/b978-0-12-409547-2.14898-x

Cited by 1 publication

(2 citation statements)

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“…Glycosidase inhibition and BNCT are disease management strategies we pursue through the design and synthesis of novel chemical entities imbued with capabilities to interact with carbohydrate-active enzymes and through the covalent linkage of organic boron to biologically active substrates [1][2][3][4][5][6][7][8][9].…”

Section: Introductionmentioning

confidence: 99%

“…The chemical behavior of organic boron, principally in its boronic acid (R-B(OH) 2 ) and boronate forms (R-B(OR')(OH), R-B(OR') 2 , R-B − (OH) 4 and R-B − (OR') 3 ), is kaleidoscopic and synthetically challenging, but provides the opportunity to produce glycosidase modulators possessing an expanded interaction profile with enzymes (extending to reversible covalent bonds via the B atom empty p-orbital) and switch on/switch off BNCT agents [1][2][3][4][5][6][7]. These capabilities-coupled with the low toxicity of organic boron moietiesmake drug leads of this type highly desirable and of paramount importance in medicinal chemistry [1,4].…”

Section: Introductionmentioning

confidence: 99%

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Diastereoselective Synthesis of the Borylated d-Galactose Monosaccharide 3-Boronic-3-Deoxy-d-Galactose and Biological Evaluation in Glycosidase Inhibition and in Cancer for Boron Neutron Capture Therapy (BNCT)

Simone

2023

Molecules

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Drug leads with a high Fsp3 index are more likely to possess desirable properties for progression in the drug development pipeline. This paper describes the development of an efficient two-step protocol to completely diastereoselectively access a diethanolamine (DEA) boronate ester derivative of monosaccharide d-galactose from the starting material 1,2:5,6-di-O-isopropylidene-α-d-glucofuranose. This intermediate, in turn, is used to access 3-boronic-3deoxy-d-galactose for boron neutron capture therapy (BNCT) applications. The hydroboration/borane trapping protocol was robustly optimized with BH3.THF in 1,4-dioxane, followed by in-situ conversion of the inorganic borane intermediate to the organic boron product by the addition of DEA. This second step occurs instantaneously, with the immediate formation of a white precipitate. This protocol allows expedited and greener access to a new class of BNCT agents with an Fsp3 index = 1 and a desirable toxicity profile. Furthermore, presented is the first detailed NMR analysis of the borylated free monosaccharide target compound during the processes of mutarotation and borarotation.

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