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The synthesis and properties of new carbohydrate‐modified mesoionic thiazolo[3,2‐α]pyrimidine‐5,7‐dione acyclonucleosides
Author(s) -
Stoelting Daniel T.,
Mbagwu Godwin O.,
Scott Tina,
Long Michael,
Sharpe Elsa L.
Publication year - 2002
Publication title -
journal of heterocyclic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.321
H-Index - 59
eISSN - 1943-5193
pISSN - 0022-152X
DOI - 10.1002/jhet.5570390416
Subject(s) - chemistry , pyrimidine , mesoionic , substituent , methanol , yield (engineering) , acetonide , nucleophile , acylation , moiety , d glucose , organic chemistry , medicinal chemistry , stereochemistry , combinatorial chemistry , catalysis , medicine , materials science , surgery , triamcinolone acetonide , metallurgy
The synthesis of the first examples of Class II mesoionic thiazolopyrimidine acyclonucleosides (MTA) incorporating the 2,3‐dihydroxypropyl moiety as the sugar simulator is described. First, 2‐bromothiazole was reacted with excess 1‐amino‐2,3‐propanediol acetonide via an aromatic nucleophilic substitution reaction to yield 1‐(2‐thiazolylamino)‐2,3‐propanediol acetonide. This acetonide intermediate was condensed at 160° with substituted bis(2,4,6‐trichlorophenyl) malonic esters to form a series of protected acyclonucleosides termed anhydro ‐(8‐((2,2‐dimethyl‐1,3‐dioxolan‐4‐yl)methyl)‐5‐hydroxy‐7‐oxothiazolo[3,2‐ a ]pyrimi‐dinium hydroxides) which differ in their 6‐position substituent. Deprotection of these acyclonucleosides using p ‐toluenesulfonic acid catalyst in methanol at 65° yielded the desired Class II MTA, anhydro ‐(8‐(2,3‐dihydroxypropyl)‐5‐hydroxy‐7‐oxothiazolo[3,2‐ a ]pyrimidinium hydroxides).