Synthesis of novel non-isoprenoid phenolic acids and 3-alkylpyridines

• Published in: Pure and applied chemistry 2005-01, Vol.77 (1), p.185-193
• Main Authors: Jain, Subhash C., Kumar, Rohtash, Goswami, Rajeev, Pandey, Mukesh K., Khurana, Shilpi, Rohatgi, Leena, Gyanda, Kapil
• Format: Article
• Language: English
• Subjects: 3-alkyl pyridines; Alkaloids; Alkylation; anacardic acids; antimicrobial; Aromatic compounds; cytotoxic; Hachijodine A & E; molluscicidal; Natural products; non-isopreniod phenolic acids; Phenolic acids; Synthesis; synthesis via sulfones
• ISSN: 0033-4545; 1365-3075
• DOI: 10.1351/pac200577010185

A new strategy has been developed for the synthesis of naturally occurring 6-alkenyl phenolic acids and 3-alkylpyridine alkaloids of biological importance. This strategy makes use of the proper substituted aryl or pyridyl sulfone as the potent intermediate. A carbanion was generated from the sulfone by treating it with NaH in dimethylformamide (DMF) at –5 °C and was used for alkylation reaction with alkyl/alkenyl bromide in DMF at 0 °C to give product, which, on reduction with sodium-amalgam, yielded the desired natural product. Using this methodology, we have synthesized 11 natural 6-alkyl/alkenyl salicylic acids, which were known to possess strong antimicrobial activities against many pathogens and had also shown molluscicidal activity against the snail . This methodology was also extended to synthesize two natural 3-alkylpyridine alkaloids that were known to possess strong cytotoxic activity against P-388 murine leukemia cells with IC values of 1–2.3 μg/ml. Taking leads from these natural products, we have also synthesized a number of related compounds in order to find a potential drug candidate for the future. This paper presents the highlights of the work done on the synthesis of these two classes of compounds.