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SYNTHESIS AND EVALUATION OF ACYCLIC SUGAR NUCLEOSIDES *
Author(s) -
Horton Derek,
Baker David C.,
Kokrady Satish S.
Publication year - 1975
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1975.tb29219.x
Subject(s) - chemistry , stereochemistry , ribose , pyrimidine , epimer , sugar , chirality (physics) , bromine , bromide , aldose , glycosidic bond , tautomer , organic chemistry , glycoside , chiral symmetry breaking , physics , quantum mechanics , nambu–jona lasinio model , enzyme , quark
Acylated aldose dialkyl dithioacetals with bromine undergo replacement of one alkylthio group by bromine. These unstable bromides react, as by fusion with 2,4-bis(trimethylsilyloxy)pyrimidine, to give acylated 1-(pyrimidin-1-yl) derivatives that upon saponification afford acyclic sugar nucleoside analogues, some as separable mixtures of 1-epimers. Systemic stereochemical variants have been conducted. Pmr conformational studies show that the sugar chain is extended in certain examples, whereas others favor folded ("sickle") conformations, in line with a general rationale developed for acyclic-sugar derivatives. Condensation of the bromides with purines gives 9-substituted acyclic-sugar nucleoside analogues; synthesized systematically for various series, these include the D-pentoses in combination with 6-mercaptopurine. In vitro and in vivo biological activities vary according to stereochemistry of the sugar. The position of substitution of the sugar chain, the chirality at C-1', and the tautomeric form of the heterocycle, were established by x-ray crystallography of the product from D-arabinose and 6-mercaptopurine. The x-ray data permit correlation of C-1 chirality throughout the series and pmr data indicate the favored conformations.