Total Synthesis of Caloporoside

• Published in: Journal of organic chemistry Vol. 63; no. 9; pp. 3072 - 3080
• Main Authors: Fürstner, Alois, Konetzki, Ingo
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 01.05.1998; Amer Chemical Soc
• Subjects: Chemistry; Chemistry, Organic; Physical Sciences; Science & Technology; PRACTICAL SYNTHESIS; ACID; OLIGOSACCHARIDES; COUPLING REACTIONS; INTRAMOLECULAR AGLYCON DELIVERY; BETA-D-MANNOPYRANOSIDES; TEMPORARY SILICON CONNECTION; 1-ALKOXY-1-GLYCOSYL RADICALS; EFFICIENT; STEREOCONTROLLED SYNTHESIS
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo9800098

The first total synthesis of the fungal metabolite caloporoside 1, a strong and selective inhibitor of phospholipase C, is described. Both sugar units of its complex disaccharidic segment were obtained from 3,4,6-tri-O-benzyl-d-glucopyranose 14 as a common building block, with d-gluco → d-manno inversions as the key strategic elements. This particular substitution reaction occurred readily on the acyclic segment (27 → 28), whereas ultrasonication was required to override adverse stereoelectronic effects upon formation of β-d-mannopyranoside unit 34. The (16R)-hydroxyheptadecylsalicylic acid part of 1 was efficiently prepared by a palladium-catalyzed Suzuki cross coupling reaction of aryltriflate 7 with the 9-alkyl-9-BBN derivative formed from alkene 6 and 9-H-9-BBN.