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CURATOR
A pinboard by
Yi-Yun Tsao

PhD Student, Texas A&M University

PINBOARD SUMMARY

DFT calculations supported that strained monomer can promote polymerization to afford DNA analogs.

A grand challenge that crosses synthetic chemistry and biology is the scalable production of functional analogs of biomacromolecules. We have focused our attention on the use of DNA building blocks bearing non-natural bases to develop a synthetic methodology that allows for the construction of high molecular weight DNA-analog polymers. Our 6-membered cyclic phosphoester ring-opening polymerization strategy was developed by an initial preparation of novel DNA analogs, comprised of butenyl-functionalized deoxyribonucleoside repeat units, connected via 3’,5’-backbone linkages. A thymidine-derived bicyclic monomer was synthesized in two steps directly from thymidine. Computational modeling of the 6-membered 3’,5’-cyclic phosphoester ring derived from deoxyribose supported the hypothesis that the strained monomer can promote ring-opening polymerization to afford the DNA-analog polymers with low dispersities. This advanced design combines the merits of natural product-derived materials and functional, degradable polymers to provide a new platform for functional, synthetically-derived DNA-analog materials.

3 ITEMS PINNED

Synthetic, Functional Thymidine-Derived Polydeoxyribonucleotide Analogues from a Six-Membered Cyclic Phosphoester.

Abstract: A grand challenge that crosses synthetic chemistry and biology is the scalable production of functional analogues of biomacromolecules. We have focused our attention on the use of deoxynucleoside building blocks bearing non-natural bases to develop a synthetic methodology that allows for the construction of high molecular weight deoxynucleotide polymers. Our six-membered cyclic phosphoester ring-opening polymerization strategy is demonstrated, herein, by an initial preparation of novel polyphosphoesters, comprised of butenyl-functionalized deoxyribonucleoside repeat units, connected via 3',5'-backbone linkages. A thymidine-derived bicyclic monomer, 3',5'-cyclic 3-(3-butenyl) thymidine ethylphosphate, was synthesized in two steps directly from thymidine, via butenylation and diastereoselective cyclization promoted by N,N-dimethyl-4-aminopyridine. Computational modeling of the six-membered 3',5'-cyclic phosphoester ring derived from deoxyribose indicated strain energies at least 5.4 kcal/mol higher than those of the six-membered monocyclic phosphoester, 2-ethoxy-1,3,2-dioxaphosphinane 2-oxide. These calculations supported the hypothesis that the strained 3',5'-cyclic monomer can promote ring-opening polymerization to afford the resulting poly(3',5'-cyclic 3-(3-butenyl) thymidine ethylphosphate)s with low dispersities (Đ < 1.10). This advanced design combines the merits of natural product-derived materials and functional, degradable polymers to provide a new platform for functional, synthetically derived polydeoxyribonucleotide-analogue materials.

Pub.: 11 Apr '17, Pinned: 28 Jun '17