First Total Synthesis of the Bioactive Arylnaphthyl Lignan 4‐O‐Glycosides Phyllanthusmin D and 4′′‐O‐Acetylmananthoside B

• Published in: European journal of organic chemistry Vol. 2017; no. 25; pp. 3674 - 3680
• Main Authors: Liu, Lei, Hu, Yang, Liu, Hui, Liu, De‐Yong, Xia, Jian‐Hui, Sun, Jian‐Song
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 07.07.2017; Wiley Subscription Services, Inc
• Subjects: Accessibility; Antitumoral agents; Arylnaphthalene; Atropisomers; Biocompatibility; Biomedical materials; Catalysis; Chemistry; Chemistry, Organic; Glycosides; Glycosylation; Lead compounds; Lignan; Physical Sciences; Science & Technology; Selectivity; Surgical implants; Toxicity; Antitumoral agents; ETOPOSIDE; DESIGN; Atropisomers; Glycosides; CLEISTANTHIN; Lignan; Glycosylation; GLYCOSYL ORTHO-ALKYNYLBENZOATES; DONORS; Arylnaphthalene
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.201700556

Based on the application of phase‐transfer‐catalysis and Yu glycosylations, the first total syntheses of the arylnaphthyl glycosides phyllanthusmin D and 4′′‐O‐acetylmananthoside B, which have been claimed to be ideal antitumoral lead compounds in terms of cytotoxicity, cytotoxic selectivity, and a new mechanism of action, were achieved. Starting from easily accessible compounds, the two target molecules were obtained with longest linear sequences of 9 and 15 steps, in overall yields of 29 and 9 %, respectively. As part of this synthetic investigation, an efficient and scalable synthetic route to diphyllin was established, and the atropisomeric phenomenon in the arylnaphthyl glycosides was also confirmed. The first total syntheses of phyllanthusmin D and 4′′‐O‐acetylmananthoside B, which have been claimed to be ideal antitumoral lead compounds in terms of cytotoxicity and selectivity, were achieved. Starting from easily accessible compounds, the two target molecules were obtained with longest linear sequences of 9 and 15 steps, in overall yields of 29 and 9 %, respectively.