Author:
Robins Morris J.,Basom Gerald L.
Abstract
Trifluoroacetylation of 2′-deoxyinosine (2), obtained by enzymatic deamination of 2′-deoxyadenosine (1), gave the 3′,5′-bis-O-trifluoroacetate (3). Reaction of the electronegatively substituted deoxynucleoside, 3, with DMF-thionyl chloride complex in refluxing methylene chloride gave a high yield of 6-chloropurine 2′-deoxyriboside (4) after deblocking.Displacement of chloride of 4 by hydrosulfide to give 6-mercaptopurine 2′-deoxyriboside (5) followed by sulfur alkylation with p-nitrobenzyl bromide gave 6-S-(p-nitrobenzyl) thiopurine 2′-deoxyriboside (6) which was alternatively prepared by displacement of chloride from 4 by p-nitrobenzyl mercaptide, generated in situ from the isothiouronium salt. Methyl mercaptide reaction with 4 gave 6-methylthiopurine 2′-deoxyriboside (7). Treatment of 4 with trimethylamine gave the corresponding quaternary ammonium chloride (8) which was allowed to react with potassium fluoride to give 6-fluoropurine 2′-deoxyriboside (9). Respective amine displacements on 4 gave 6-benzylaminopurine 2'-deoxyriboside (10), and 6-hydroxylaminopurine 2′-deoxyriboside (11). Reaction of 4 with liquid ammonia completed the first reported transformation of 2′-deoxyinosine (2) to 2′-deoxyadenosine (1).Biological rationale for the synthesis of these 2′-deoxynucleosides and their evaluation as substrates of adenosine deaminase are discussed. Major mass spectral fragmentations are tabulated.
Publisher
Canadian Science Publishing
Subject
Organic Chemistry,General Chemistry,Catalysis
Cited by
103 articles.
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