THE SYNTHESIS AND EVALUATION OF AZAPURINE NUCLEOSIDES AS CYTOTOXIC AGENTS^*

8-Azaadenosine. Crystal structure of its monohydrate and conformational analysis for rotation around the glycosyl bond

“…The glycosyl bond, N(9)-C(V), with a distance of 1.447 (3) Á, is about 0.02 A shorter than the glycosyl bond distance reported for adenosine16 and for other purine nucleosides.26 As documented elsewhere,7 this may be indicative of a general shortening of the glycosyl bond in ortho azanucleosides of both the purine and the pyrimidine type.…”

Analogs of 8-azaguanosine

“…These compounds proved to be substrates for adenosine kinase, to be cytotoxic to cell lines possessing this enzyme but not to lines deficient in it, and to show some activity against murine leukemias.1,5 These initially encouraging results and the knowledge of the anticancer activity of 6-thioguanine3 and 8-azaguanine (5-amino-3,6-dihydro-7ff-l,2,3-triazolo [4,5-d]pyrimidin-7-one)6 suggested the preparation and reevaluation of the known 8-aza-6-thioguanine (5-amino-3,6-dihydro-7if-l,2,3-triazolo[4,5-d]pyrimidine-7-thione) (25a)7 and the synthesis of its ribonucleoside 17 since, although 6-thioguanosine is rapidly phosphorylyzed to 6-thioguanine,3 8-azapurine ribonucleosides such as 8-azainosine are not and show activity not possessed by the parent heterocycles. 1,2 The successful synthesis of 7-(methylthio)-3-(2,3,5tri-O-acetyl-0-D-ribofuranosyl)-3H-l,2,3-triazolo [4,5-d]-pyrimidine8 by the molecular sieve catalyzed reaction of 7-(methylthio)-3H-l,2,3-triazolo [4,5-d]pyrimidine with 2,3,5-tri-O-acetyl-D-ribofuranosyl chloride and the reactivity of the methylthio group of this nucleoside to nucleophilic displacement reactions8,9 suggested a similar sequence for the preparation of 8-aza-6-thioguanosine (5-amino-3,6-dihydro-3-j3-D-ribofuranosyl-7if-l,2,3-triazolo [4,5-d]pyrimidine-7-thione, 17).…”

2‐Azapurine Nucleosides: Synthesis, Properties, and Base Pairing of Oligonucleotides

“…2-Azahypoxanthine is also formed by photolytic degradation of dacarbazine (DTIC), a chemotherapeutic agent employed in the treatment of various types of cancer including Hodgkins disease, malignant melanomas, soft tissue sarcomas, and advanced neuroblastomas [4]. Also, 2-azapurine (imidazo [4,5-d] [1,2,3]triazine) ribonucleosides possess significant biological activities [5a] [6] [7]. Up to now, 2-azapurine nucleosides have not been found as natural products, but recently 2-azahypoxanthine has been isolated from the fairy-ring forming fungus Lepista sordida [8].…”