Nucleic Acid Related Compounds. 5. The Transformation of Formycin and Tubercidin into 2′- and 3′-Deoxynucleosides

Abstract

Reaction of tubercidin (4-amino-7-~-~-ribofuranosylpyrrolo[2,3-d]pyrimidine)(1) with a-acetoxyisobutyryl chloride in the presence of excess sodium iodide in acetonitrile gave an acylated iodo intermediate (2) which was converted into 3'-deoxytubercidin (4) by hydrogenolysis and subsequent saponification.Analogous treatment of formycin (7-amino-3-~-~-ribofuranosylpyrazo10[4,3-d]pyrimidine) (5) gave 3'-deoxyformycin (6) and 2'-deoxyformycin (7) in an approximate ratio of 3:2. These purified nucleosides, 6 and 7 were individually deaminated enzymatically to give 3'-deoxyformycin B (8) and 2'-deoxyformycin B (9).Biological rationale, n.m.r., and mass spectra of these antibiotic-derived deoxynucleosides are discussed.La rCaction de la tubercidine (amino-4 p-D-ribofuranosyl-7 pyrrolo pyrimidine [2,3-dl) (1) avec le chlorure d'a-acetoxyisobutyryle en presence d'un exces d'iodure de sodium dans I'acttonitrile donne un intermediaire iodo acylC (2) qui a etC transforme en deoxy-3' tubercidine (4) par hydroginolyse suivie d'une saponification.Le traitenlent identique de la formycine (amino-7 a-D-ribofuranosyl-3 pyrazolo pyrimidine [4,3-dl) (5) donne la dioxy-3' formycine (6) et la dioxy-2' formicyne (7) dans un rapport approximativement Cgal a 3:2. Les nucleosides purifies, 6 et 7, donnent respectivement la deoxy-3'formycine B(8) et la dkoxy-2' formycine B(9) lorsque I'on enleve leur groupement amine par action enzymatique.Les caracteristiques biologiques ainsi que les spectres de masse et r.m.n. de ces dCoxynuclCosides derives d'antibiotiques sont discutts.[Traduit par le journal]Can. J. Chern., 5 1 . 1313 (1973) We wish to report the synthesis of 3'-deoxyThe nucleoside antibiotics tubercidin (1) and tubercidin (4), 3'-deoxyformycin (6), and 2'-formycin (5) have been studied in considerable deoxyformycin (7) using the "abnormal" reaction detail in biological systems and a comprehensive of a-acetoxyisobutyryl halides with diols dis-review is available (3). Formycin (5) is currently covered by Mattocks (1) and first applied to undergoing investigation in molecular biology nucleosides by Moffatt and coworkers (2).

The Chemistry of C-Nucleosides

“…The overall yield of 543 from 536 was 36%. The IH NMR spectrum of 543 was very similar to that reported (315,316) for 2'-deoxyformycin B (503) by Robins et al, but rather different from that reported by Rao et al (330) The H-I' signal of 543 at O 5.22 appeared as a double of doublet as that reported for 2'-deoxyformycin B (505), but not an apparent triplet as reported for 535. Deprotection of 543 by hydrogenolysis over palladium hydroxide (Degussa type) afforded 2'-deoxy-9-deazaadenosine, which also showed a double of doublet for H-I'.…”

“…(317) 2'-Deoxyformycin B (505) and 3'-deoxyformycin B (504) were prepared by deamination of 503 and 502, respectively, with calf intestinal deaminase. (316) When I{I-uridine was treated with 2-acetoxyisobutyryl chloride (267,318) in various solvents, a mixture of several compounds was obtained. These components were chromatographically separated and the two major products (after saponification) were identified as the 2'-chloro-ribosyl (508) and 3'-chloro-xylosyl (509) nucleosides, and two minor components as 2,4'-anhydro-(506) and 2'-chloro-arabinosyl nucleosides (507) (Scheme 45).…”

Nucleic acid related compounds. 24. Transformation of tubercidin 2′,3′-O-orthoacetate into halo, deoxy, epoxide, and unsaturated sugar nucleosides

“…In contrast to the corresponding reaction of the adenosine orthoester (9), no 2'-chloro isomers were detected. The absence of nucleophilic attack at the 2'-position of tubercidin has been noted previously in acetoxonium ion mediated reactions (5,6). The use of free radical dechlorination conditions (10) (tri-12-butyltin hydride plus a,al-azobisisobutyronitrile as initiator) with 3a followed by deblocking gave 3'-deoxytubercidin (8) (5,6) in 517, yield.…”

“…The absence of nucleophilic attack at the 2'-position of tubercidin has been noted previously in acetoxonium ion mediated reactions (5,6). The use of free radical dechlorination conditions (10) (tri-12-butyltin hydride plus a,al-azobisisobutyronitrile as initiator) with 3a followed by deblocking gave 3'-deoxytubercidin (8) (5,6) in 517, yield. This allows use of the blocked chloro nucleosides for syntheses of specific deoxy derivatives whereas catalytic hydrogenolysis of chloro compounds has been generally unsuccessful (6,11).…”

“…However, little work has been reported concerning the sugar moiety of tubercidin (3)(4)(5)(6). Although the well established sugar-base coupling methods have been used extensively in the synthesis of modified sugar analogs of adenosine (7), no such parallel studies have appeared with related tubercidin compounds.…”