Adenosine 2 ,3’-dideoxy-, preparation

Another route for the synthesis of azidonucleosides involved the transformation of preformed 3 -azido-2, 3 -dideoxynucleosides. These transformations usually follow standard procedures in nucleoside chemistry. 3 -Azido-2, 3 -dideoxy-inosine 7d has been prepared by deamination of the adenosine analogue 7a with adenosine deaminase [54]. A variety of 3 -azido-2, 3 -dideoxycytidine derivatives, such as 7b [36-38, 50], 7g [38], 7h [38], and 7i [38] have been prepared from the corresponding 3 -azido-2, 3 -dideoxyuridine and thymidine derivatives following known procedures for the amination at position 4. 3 -Azido-2, 3 -dideoxyuridine 7f has also been used as starting material for the synthesis of a variety of 3 -azido-2, 3 -dideoxy-5-substituted uridines, such as 7j-7m and 7p-7t [38, 51, 53]. 

Treatment of 5-deoxy-5-halogeno nucleosides of adenine and uracil with trimethylamine yielded the corresponding 5-deoxy-5-trimethylammonium salts, whose interaction with anionic polynucleotides was then examined. Various A -alkyl, A -cycloalkyl, and iV-alkaryl derivatives of 3-amino-3-deoxy-and 3, 5 -diamino-3, 5 -dideoxy-adenosine have been prepared from the amino-sugar nucleosides the 3 -benzylamino derivative gave the unusual oxazolidine derivative (52). ° ... 

Nucleophilic attack on 2, 3 -cyclic sulfates of inosine and adenosine occurs predominantly at C-3, and in this way the 3 -deoxy-3 -fluoroxylofuranosides 66 (X=F) were prepared. 5-Chloro-2, 3 -dideoxy-3 -fluorouridine labelled with tritium at C-5 has been prepared by an oxidation-reduction sequence, and the 2-0-ethyl analogues of 3 -fluoro-2, 3 -dideoxyuridine and 3 -fluorothymidine have been made by silyl base-sugar coupling procedures. ... 

The oxorhenium(V) complex 80 has been prepared from 2, 3 -diamino-2, 3 -dideoxyadenosine, and exists as a 2 1 mixture of syn- and an/i-isomers. Both were inhibitors of purine-specific ribonuclease, with the 57/i-isomer being more effective. " The same group has described a route to 3, 5 -diamino-3, 5 -dideoxy-adenosine (82) from the /> xo-epoxide 81 (Vol. 25, p. 251-2), as outlined in Scheme 10. The Mitsunobu inversion using benzyl alcohol as nucleophile is noteworthy, and proved superior to other strategies. An oxorhenium(V) complex was also formed from 82." Thymidine can be converted into the anhydronucleo-side 83 by two successive Mitsunobu reactions, and 83 was converted into the aminoderivative 84 of AZT, and some phosphoramidates were produced from 84." Some 5 -deoxy-5 -sulfonylamido derivatives of AZT have also been produced by successive displacements at 0-5 and 0-3 by nitrogen nucleophiles." ... 

An intermediate prepared from isopropylidene-D-glyceraldehyde via a Claisen rearrangement and previously used for the synthesis of some branched-chain fluorinated nucleosides (Vol. 32, p. 272-273), has now been used to make a fluorinated cyclopentane unit, to which was linked 6-chloropurine, thus leading to carbocyclic 2, 3 -dideoxy-4 -fluoro-L-adenosine (161). The same synthetic sequence could be modified to generate, via a metathesis step, an enantiomeric cyclopentane unit, and hence the enantiomer of 161, and equivalent structures with the other nucleobases. ... 

Tubercidin (7-deaza-adenosine) (535) has been converted, via treatment of its 2, 3 -0-methoxyethylidene derivative with pivaloyl chloride in refluxing pyridine, into A -epi-, 3 -deoxy-, and 2, 3 -dideoxy-tubercidin. 2, 3 -Anhydrotubercidin was also prepared and converted into its 2, 3 -anhydro-jS-D-lyxofuranosyl analogue. These epoxides were then used to prepare D-xylo and D-arabino analogues [(536) and (537), respectively] of tubercidin. 7-Methyltubercidin (538) and its a-anomer have been prepared from the products obtained on condensation of 2,3,5-tri-O-benzyl-D-ribofuranosyl bromide and an appropriately protected 7-methylpyrrolo[2,3-d] pyrimidine. ... 

A direct conversion of rlbonucleosides into 2 ,3 -dideoxy tems has been applied to the synthesis of ddU (Scheme 5) dideoxy-adenosine and --Inosine could be subsequently prepared by microbiological base exchange.55... 

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