Oligomeric Phosphate Diesters (OPDs)

          Boron-rich oligomeric phosphate diesters (OPDs) are attractive boron delivery vehicles for use in BNCT. They are readily obtained from selected carborane-containing dihydroxy precursors and assembled using well-established phosphoramidite coupling chemistry. In addition, boron-rich OPDs are inherently hydrophilic or amphiphilic by virtue of their anionic phosphate backbone. Hawthorne and co-workers first examined the automated synthesis of selected OPDs using standard DNA synthesizer techniques. Carboranyl phosphoramidites, such as 1, are routinely prepared in good yield and efficiently coupled to form boron-rich OPDs such as 2 without modification of the standard conditions for the automated synthesis of DNA.

          As an example, the oligophosphate chain 2 contains 100 boron atoms with the sequence beginning with a commercially available thymine residue, and ending with an amino group incorporated at the conclusion of the automated synthesis. Compound 2 is water-soluble (> 75 mg/ml) and its hydrophilicity is enhanced through the conversion of the closo-carborane cages to their corresponding anionic nido-derivatives by heating with ammonium hydroxide. The fast (< 5 min per coupling cycle), efficient (> 98% coupling efficiency per step) and flexible methodology for the automated synthesis of species such as 2 lends itself to the synthesis of a vast library of designed boron-rich oligomers such as those shown in Figure 2 and others in which single strands of DNA or other biomolecules may be attached.

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