Total Synthesis of Polycavernosides A and B, Two Lethal Toxins from Red Alga

• Published in: Journal of organic chemistry Vol. 82; no. 24; pp. 13204 - 13219
• Main Authors: Iwasaki, Kotaro, Sasaki, Satori, Kasai, Yusuke, Kawashima, Yuki, Sasaki, Shohei, Ito, Takanori, Yotsu-Yamashita, Mari, Sasaki, Makoto
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 15.12.2017; Amer Chemical Soc
• Subjects: Bacterial Toxins - chemistry; Chemistry; Chemistry, Organic; Disaccharides - chemical synthesis; Disaccharides - chemistry; Glycosylation; Macrolides - chemical synthesis; Macrolides - chemistry; Molecular Structure; Physical Sciences; Rhodophyta - chemistry; Science & Technology; CYANOBACTERIUM LYNGBYA-BOUILLONII; SECONDARY ALCOHOLS; GRACILARIA-EDULIS; CROSS-COUPLING REACTIONS; TETRAHYDROPYRAN SUBUNIT; GLYCOSIDIC MACROLIDE; CONNECTIVE APPROACH; MARINE CYANOBACTERIUM; 1,3-DIOL ACETONIDES; CONVERGENT SYNTHESIS
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/acs.joc.7b02293

Polycavernosides A and B are glycosidic macrolide natural products isolated as the toxins causing fatal human poisoning by the edible red alga Gracilaria edulis (Polycavernosa tsudai). Total synthesis of polycavernosides A and B has been achieved via a convergent approach. The synthesis of the macrolactone core structure is highlighted by the catalytic asymmetric syntheses of the two key fragments using hetero-Diels–Alder reaction and Kiyooka aldol reaction as the key steps, their union through Suzuki–Miyaura coupling, and Keck macrolactonization. Finally, glycosylation with the l-fucosyl-d-xylose unit and construction of the polyene side chain through Stille coupling completed the total synthesis of polycavernosides A and B.