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Oligonucleosides with a Nucleobase‐Including Backbone, Part 4, A Convergent Synthesis of Ethynediyl‐Linked Adenosine Tetramers
Author(s) -
Gunji Hiroki,
Vasella Andrea
Publication year - 2000
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 - 10.1002/1522-2675(20001220)83:12<3229::aid-hlca3229>3.0.co;2-s
Subject(s) - chemistry , tetramer , intramolecular force , dimer , substituent , iodide , cycloaddition , stereochemistry , medicinal chemistry , azide , nucleobase , amine gas treating , organic chemistry , dna , biochemistry , enzyme , catalysis
Deprotection of the tetramer 24 , obtained by coupling the iodinated dimer 18 with the alkyne 23 gave the 8′,5‐ethynediyl‐linked adenosine‐derived tetramer 27 ( Scheme 3 ). As direct iodination of C(5′)‐ethynylated adenosine derivatives failed, we prepared 18 via the 8‐amino derivative 17 that was available by coupling the imine 15 with the iodide 7 ; 15 , in its turn, was obtained from the 8‐chloro derivative 12 via the 4‐methoxybenzylamine 14 ( Scheme 2 ). This method for the introduction of the 8‐iodo substituent was worked out with the N ‐benzoyladenosine 1 that was transformed into the azide 2 by lithiation and treatment with tosyl azide ( Scheme 1 ). Reduction of 2 led to the amine 3 that was transformed into 7 . 1,3‐Dipolar cycloaddition of 3 and (trimethylsilyl)acetylene gave 6 . The 8‐substituted derivatives 4a – d were prepared similarly to 2 , but could not be transformed into 7 . The known chloride 8 was transformed into the iodide 11 via the amines 9 and 10 . The amines 3 , 10 , and 16 form more or less completely persistent intramolecular C(8)N−H⋅⋅⋅O(5′) H‐bonds, while the dimeric amine 17 forms a ca . 50% persistent H‐bond. There is no UV evidence for a base‐base interaction in the protected and deprotected dimers and tetramers.