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Carbocyclic Analogs of Nucleosides. Part 4. Preparation of enantiomerically pure analogs of purine nucleosides for the synthesis of sulfone‐linked oligonucleotide analogs
Author(s) -
Jenny Thomas F.,
Benner Steven A.
Publication year - 1993
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.19930760207
Subject(s) - chemistry , stereochemistry , depurination , nucleoside , oligonucleotide , nucleobase , hydroxymethyl , purine , mitsunobu reaction , phosphodiester bond , nucleoside analogue , combinatorial chemistry , organic chemistry , biochemistry , enzyme , dna , rna , gene
Cyclopentane derivatives bearing a 3‐(hydroxymethyl) group, a 4‐(2‐hydroxyethyl) functionality, and a nucleoside base are carbocyclic variants of nucleoside analogs previously described as building blocks for the preparation of oligonucleotide analogs having dimethylene sulfone (= methanosulfonylmethano) linking groups replacing the phosphodiester linking units found in natural oligonucleotides. These carbocyclic nucleoside analogs ( e.g . 17 and 20 ) are stable to both acid‐catalyzed depurination and base‐catalyzed hydrolysis, in contrast with most non‐ionic analogs of oligonucleotides. Furthermore, they can be prepared with complete control over the stereochemistry at the ‘anomeric’ center. A procedure is given for preparing these purine‐nucleoside analogs via the construction of an enantiomerically pure carbocyclic skeleton ( Schemes 1–3 ), followed by a Mitsunobu ‐type reaction to introduce the purine‐base derivatives ( Scheme 4 ). Furthermore, preliminary results for the coupling of these analogs to yield nucleoside dimers ( e.g. 26 ) are also reported ( Scheme 5 ).