| Summary: | Drug leads with a high Fsp<sup>3</sup> 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 <span style="font-variant: small-caps;">d</span>-galactose from the starting material 1,2:5,6-di-<i>O</i>-isopropylidene-α-<span style="font-variant: small-caps;">d</span>-glucofuranose. This intermediate, in turn, is used to access 3-boronic-3deoxy-<span style="font-variant: small-caps;">d</span>-galactose for boron neutron capture therapy (BNCT) applications. The hydroboration/borane trapping protocol was robustly optimized with BH<sub>3</sub>.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 Fsp<sup>3</sup> 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.
|
|---|