Synthesis and biological activity of certain derivatives of oxazinomycin and related oxadiazole nucleosides

Abstract

Oxazinomycin was converted into 2',3',5'-tri-O-acetyloxazinomycin (2) and 2',3'-O-isopropylideneoxazinomycin (3), respectively. Compound 3 was iodinated and reduced to provide 5'-deoxy-2',3'-O-isopropylideneoxazinomycin (5) which, after acid hydrolysis, provided 5'-deoxyoxazinomycin (6). Alternatively, the iodination of oxazinomycin followed by catalytic hydrogenation also provided 6. Oxazinomycin was treated with 2-acetoxybenzoyl chloride to provide 3'-O-acetyl-2'-chloro-2'-deoxyoxazinomycin (8) which, after reduction with tributyltin hydride, provided 3'-O-acetyl-2'-deoxyoxazinomycin (9). Oxazinomycin was also converted into oxazinomycin 5'-phosphate (10) and into O4,2'-anhydrooxazinomycin (11). 1,2,4-Oxadiazole-3,5-dione (12) was glycosylated to provide 2-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)-1,2,4-oxadiazole-3,5-dione (13) which, after deacetylation, provided 2-beta-D-ribofuranosyl-1,2,4-oxadiazole-3,5-dione (14). Similarly, 12 provided 2-(2-deoxy-beta-D-erythro-pentofuranosyl)-1,2,4-oxadiazole-3,5-dione (17); 14 was also converted into the corresponding 2',3'-O-isopropylidene derivative 15. Compound 14 showed significant antiviral activity against herpes simplex virus type 1, in vitro.

Beyond the approved: target sites and inhibitors of bacterial RNA polymerase from bacteria and fungi

“…468,469 Several derivatives of OZM exist, however, they mostly lack the antitumor activity of OZM. 471…”

“…OZM contains an oxazine chromophore consisting of a unique 1,3-oxazine-2,4-dione ring which is linked to a 5-b-D-ribofuranosyl moiety. 467,470 This oxazinedione ring system is quite susceptible to hydrolytic cleavage rendering the compound less stable than uridine or c. 471 The BGC for OZM production was only recently described in 2019. 472 OZM has activity against both Gram-positive (B. subtilis and S. aureus strains) and Gram-negative bacteria (E. coli strains), as well as antitumor activity.…”

“…468,469 Several derivatives of OZM exist, however, they mostly lack the antitumor activity of OZM. 471 The MoA of OZM was characterized in 2019. 473 OZM, similarly to PUM, competes with uridine-5 0 -triphosphate (UTP) as an RNAP substrate and inhibits the transcription.…”

Synthesis and Biological Evaluation of Novel Bis[1,2,4]triazolo[3,4-b] [1,3,4]oxadiazoles

“…Further, there is no report on the triazolefused oxadiazole of bis‐heterocyclic systems. On the other hand, 1,3,4‐oxadiazole derivatives were reported to possess significant antibacterial , anti‐inflammatory , tyrosinase inhibitory , antiviral , antihypertensive , cortical muscarinic receptor agonists , herbicidal , Ca +2 channel blocker , antitumour , anticonvulsant , anti‐elmintic , and antioxidant activities .…”

Synthesis and Antimicrobial Activity of Linked Heterocyclics Containing Pyrazole and Oxadiazoles

“…Some aryl pyrazoles were reported to have nonnucleoside human immunodeficiency virus‐1 reverse transcriptase inhibitory , COX‐2 inhibitory , activator of the nitric oxide receptor and soluble guanylate cyclase activity . In addition, 1,3,4‐oxadiazole derivative were reported to possess significant antibacterial and anti‐inflammatory , tyrosinase inhibitory , antiviral , antihypertensive , cortical muscarinic receptor agonists , herbicidal , Ca 2+ channel blocker , antitumour , anticonvulsant , antielmintic , and antioxidant activities . In view of these reports and in continuation of our ongoing research on the synthesis of new heterocyclic compounds , it was thought of interest to accommodate pyrazole, oxadiazole moieties in a single molecular frame work and to obtain a new class of heterocyclic compounds with potential biological activity.…”