RCM-Based Synthesis of a Variety of β-C-Glycosides and Their in Vitro Anti-Solid Tumor Activity

• Published in: Journal of organic chemistry 2005-02, Vol.70 (3), p.829-836
• Main Authors: Postema, Maarten H. D, Piper, Jared L, Betts, Russell L, Valeriote, Frederick A, Pietraszkewicz, Halina
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - pharmacology; Carbohydrates with 4, 5, 6, ... C atoms, dissacharides and oligosaccharides; Carbohydrates. Nucleosides and nucleotides; Cell Line, Tumor; Chemistry; Cyclization; Drug Screening Assays, Antitumor; Esterification; Exact sciences and technology; Glycolipids - chemical synthesis; Glycolipids - chemistry; Glycolipids - pharmacology; Glycosides - chemical synthesis; Glycosides - chemistry; Glycosides - pharmacology; Humans; Lipids; Organic chemistry; Preparations and properties
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo040254t

The synthesis of a number of biologically relevant C-glycosides has been carried out through the use of an esterification−ring-closing metathesis (RCM) strategy. The required acid precursors were readily prepared via a number of standard chemical transformations followed by dehydrative coupling of these acids with several olefin alcohols 1 to yield the precursor esters 3 in excellent yield. Methylenation of the esters 3 was followed by RCM and in situ hydroboration−oxidation of the formed glycals to furnish the protected β-C-glycosides 6 in good overall yield. Several examples were converted to the corresponding C-glycoglycerolipids 17 and subsequently screened against solid-tumor cell lines for in vitro differential cytotoxicity.