%0 Journal Article
%A Tsao, Yi-Yun
Timothy
%A Wooley, Karen L.
%D 2017
%T Synthetic,
Functional Thymidine-Derived Polydeoxyribonucleotide
Analogues from a Six-Membered Cyclic Phosphoester
%U https://acs.figshare.com/articles/journal_contribution/Synthetic_Functional_Thymidine-Derived_Polydeoxyribonucleotide_Analogues_from_a_Six-Membered_Cyclic_Phosphoester/4834373
%R 10.1021/jacs.7b01116.s001
%2 https://acs.figshare.com/ndownloader/files/8025143
%K strain energies
%K weight deoxynucleotide polymers
%K degradable polymers
%K diastereoselective cyclization
%K 2-
%K dimethyl -4-aminopyridine Computational modeling
%K ring-opening polymerization
%K scalable production
%K six-membered monocyclic phosphoester
%K Six-Membered Cyclic Phosphoester
%K product-derived materials
%K six-membered cyclic phosphoester ring-opening polymerization strategy
%K polydeoxyribonucleotide-analogue materials
%K Functional Thymidine-Derived Polydeoxyribonucleotide Analogues
%K thymidine-derived bicyclic monomer
%K butenyl-functionalized deoxyribonucleoside
%K non-natural bases
%K novel polyphosphoesters
%K thymidine ethylphosphate
%K deoxynucleoside building blocks
%X 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.
%I ACS Publications