Design and Synthesis of Some Novel Oxiconazole-Like Carboacyclic Nucleoside Analogues, as Potential Chemotherapeutic Agents

✍ Scribed by Mohammad Navid Soltani Rad; Ali Khalafi-Nezhad; Somayeh Behrouz

• Publisher: John Wiley and Sons
• Year: 2009
• Tongue: German
• Weight: 290 KB
• Volume: 92
• Category: Article
• ISSN: 0018-019X
• DOI: 10.1002/hlca.200900051

✦ Synopsis

Abstract

The syntheses of some novel carboacyclic nucleosides, 17a–17o, containing oxiconazole‐like scaffolds, are described (Schemes 1–3). In this series of carboacyclic nucleosides, pyrimidine as well as purine and other imidazole derivatives were employed as an imidazole successor in oxiconazole. These compounds could be prepared in good yields by using two different strategies (Schemes 1 and 2). Due to Scheme 1, the N‐coupling of nucleobases with 2‐bromoacetophenones was attained for 18a–18e, and their subsequent oximation affording 19a–19e and finally O‐alkylation with diverse alkylating sources resulted in the products 17a–17g, 17n, and 17o. In Scheme 2, use of 2‐bromoacetophenone oximes 20, followed by N‐coupling of nucleobases, provided 19f–19j whose final O‐alkylation produced 17h–17m (Scheme 2). For the rational interpretation of the dominant formation of (E)‐oxime ethers rather than (Z)‐oxime isomers, PM3 semiempirical quantum‐mechanic calculations were discussed and the calculations indicated a lower heat of formation for (E)‐isomers.