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A Practical Synthesis of 3′‐Thioguanosine and of Its 3′‐Phosphoramidothioite (a Thiophosphoramidite)
Author(s) -
MatulicAdamic Jasenka,
Beigelman Leonid
Publication year - 1999
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/(sici)1522-2675(19991215)82:12<2141::aid-hlca2141>3.0.co;2-2
Subject(s) - chemistry , guanosine , bromide , derivative (finance) , organic chemistry , combinatorial chemistry , stereochemistry , biochemistry , financial economics , economics
Starting from guanosine, an efficient method for the synthesis of 3′‐thioguanosine (see 13 ) and of its 3′‐phosphoramidothioite (see 23 ), suitable for automated incorporation into oligonucleotides, was developed. Reaction of 5′‐ N 2 ‐protected guanosine with 2‐acetoxyisobutyryl bromide afforded stereoselectively the 2′‐ O ‐acetyl‐3′‐bromo‐ β ‐ D ‐xylofuranosyl derivative 3 , which was converted to a 7 : 3 mixture of the S ‐acyl ribofuranosyl intermediates 5 or 6 and the 3′,4′‐unsaturated by‐product 4 . The S ‐acylated nucleosides 5 and 6 were then converted in three steps to 5′‐ O ‐(4,4′‐dimethoxytrityl)‐3′‐ S ‐(pyridin‐2‐ylthio)‐3′‐thioguanosine ( 11 ), which served as a common intermediate for the preparation of free 3′‐thionucleoside 13 and 3′‐thionucleoside 3′‐phosphoramidothioite 23 .