An efficient synthesis tetrazole and oxadiazole analogues of novel 2′-deoxy-C-nucleosides and their antitumor activity

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:30

Article

Penjarla, Srishylam^1,2  Sabui, Subir Kumar¹  Reddy, Dhande Sudhakar¹  Banerjee, Shyamapada¹  Reddy, Paidi Yella¹  Penta, Santhosh²  Sanghvi, Yogesh S.^1,3 

[1] Sapala Organ Pvt Ltd, Plot Nos 146B & 147 IDA Mallapur,Phase 2, Hyderabad 500076, Telangana, India

[2] Natl Inst Technol Raipur, Dept Chem, GE Rd, Raipur 492010, Chhattisgarh, India

[3] Rasayan Inc, 2802 Crystal Ridge Rd, Encinitas, CA 92024 USA

关键词: C-Nucleoside;    Cyano-sugar;    Hoffer's Chloro-sugar;    Anomers;    Antitumor;   

DOI  :  10.1016/j.bmcl.2020.127612

来源: Elsevier

【 摘 要 】

Various tetrazole and oxadiazole C-nucleoside analogues were synthesized starting from pure alpha or beta-glycosylcyanide. The synthesis of glycosyl-cyanide as key precursor was optimized on gram-scale to furnish crystalline starting material for the assembly of C-nucleosides. Oxadizole C-nucleosides were synthesized via two independent routes. First, the glycosyl-cyanide was converted into an amidoxime which upon ring closure offered an alternative pathway for the assembly of 1,2,4-oxadizoles in an efficient manner. Second, both anomers of glycosyl-cyanide were transformed into tetrazole nucleosides followed by acylative rearrangement to furnish 1,3,4-oxadiazoles in high yields. These protocols offer an easy access to otherwise difficult to synthesize C nucleosides in good yield and protecting group compatibility. These C-nucleosides were evaluated for their antitumor activity. This work paves a path for facile assembly of library of new chemical entities useful for drug discovery.

【 授权许可】

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