| Phosphate-modified nucleic acids have found wide applications in enzymology, molecular biology and nucleic acid therapy. In this dissertation, the first designs and syntheses of new classes of boron-containing phosphodiester and phosphate mimics are described. The nucleic acid analogues include nucleoside 3′,5′-cyclic boranomonophosphates 1, nucleoside α-P-boranodiphosphates 2, boranophosphorothioates 3 [S = P–BH3] −, 5′-S-boranophosphoro-thiolates 4 [5′-S–P–BH3]− , 3′-S-borano-phosphoro-thiolates 5 [3′-S–P–BH3]−, 5′-NH-boranophosphoramidates 6 [3 ′-NH–P–BH3]−, 3 ′-NH-boranophosphoramidates 7 [3′ -NH–P–BH3]−, boranomethylphosphonates 8 [CH3–P–BH3] (uncharged), cyanoboranophosphates 9 [O = P–BH2CN]−, nucleoside thioboranomonophosphates 12, nucleoside cyanoboranomonophosphates 13, nucleoside boranothiotriphosphates 14, and cyanoboranotriphosphates 15. All except 8 are negatively charged around pH 7. Chemical structures were established via spectroscopic methods, and some chemical and biochemical properties were investigated. In addition, boranophosphorylating reagents were developed for direct boranophosporylation and the first synthesis of nucleoside β-P-boranodiphosphates 10 and γ-P-boranotriphosphates 11.*.;These boron-containing phosphodiester and phosphate mimics constitute entirely new and intriguing classes of modified nucleic acids. Their similarity to natural nucleic acid and unique properties such as increased nuclease resistance and enhanced lipophilicity, in conjunction with their potential utility as carriers of 10B in boron neutron capture therapy (BNCT) for the treatment of cancer, make them promising candidates for mechanistic, diagnostic and therapeutic applications.;*Please refer to dissertation for diagrams. |
