Efficient glycosylation of natural Danshensu and its enantiomer by sugar and 2-deoxy sugar donors. (2nd May 2018)

• Record Type: Journal Article
• Authors: Sidoryk, Katarzyna; Cmoch, Piotr; Świtalska, Marta; Trzaskowski, Bartosz; Wietrzyk, Joanna; Cybulski, Marcin
• Is Part Of: Carbohydrate research. Volume 460(2018)
• Page Start: 19
• Page End: 28
• Publication Date: 2018-05-02
• Subjects: Polyphenolic acids -- Glycosylation -- 2-Deoxy sugar -- Cytotoxic activity; Carbohydrates -- Periodicals; Chemistry, Organic -- Periodicals; Biochemistry -- Periodicals; Carbohydrates -- Periodicals; Chimie organique -- Périodiques; Glucides -- Périodiques; Biochemistry; Carbohydrates; Chemistry, Organic; Periodicals; Electronic journals; 507.78
• DOI: 10.1016/j.carres.2018.02.005
• Languages: English
• ISSNs: 0008-6215

Abstract

Abstract: An efficient methodology of the glycosylation process of a secondary plant metabolite ( R -Danshensu) and its enantiomer by sugar and 2-deoxy sugar donors was developed. The overall synthesis of the new sugar derivatives involved two steps, starting from the previously synthesized protected R and S Danshensu (1 and2 ). The deoxy sugar derivatives of R and S Danshensu were obtained from available tri-O-acetyl-2-deoxy-D-glucal and di-O-acetyl-2-deoxy-D-ramnal. The direct glycosylation of1 and2 using glycal activation by an acid catalyst in all cases led to the α-anomers of deoxy sugar derivatives with good yields. As a result, a novel group of sugar and deoxy sugar conjugates with optically pure polyphenolic acids was successfully synthesized and their cytotoxic profile against two cancer cell lines was tested. An advantageous ADME profile and antiproliferative data classified this new group of compounds as a promising scaffold for further modification of more potent and selective anticancer agents. Graphical abstract: Highlights: An efficient methodology of Danshensu (DSS) glycosylation was developed. Sugar and 2-deoxysugar derivatives of R and S Danshensu were synthesized. The ADME profile of new compounds, R -Danshensu, S -Danshensu and RA, was performed. Studies on the cytotoxic activity against tumor cell lines were completed. Compounds9, 15, 16 showed a twice better activity in comparison to that of DSS.