Syntheses and biological evaluation of new glyco-modified angucyclin-antibiotics

authored by

Andreas Kirschning, Guang Wu Chen, Gerald Dräger, Ingrid Schuberth, Lutz F. Tietze

Abstract

The synthesis of novel aquayamycin-derived angucycline antibiotics 13a-d has been achieved. Glycosylation of aquayamycin (6) using 2-selenoglycosyl acetate 7 as glycosyl donor proceeded in excellent yield but attempts to reductively remove the selenyl group led to rearrangement or further aromatization of the aglycon. As a consequence of these results, it became possible to prepare urdamycinone B (10) starting from aquayamycin (6). In addition, silyl protected D-olivals 12a,b were attached to the C-glycoside domain of aquayamycin (6) under protic conditions. As expected, the hydroxy and phenol groups of the benz[a]anthracene framework of 6 did not react under the glycosylation conditions employed. Stepwise removal of the silyl protecting group starting with tetrabutyl ammonium fluoride followed by use of the HF/pyridine complex suppressed a possible rearrangement of the aglycon and successfully terminated the sequence. The new angucycline-antibiotics 13a and 13b are some of the most potent xanthine oxidase inhibitors known and show cytotoxic activity with ED₅₀-values in the range of 12.6-2.9x10^-6 M Copyright (C) 2000 Elsevier Science Ltd.

External Organisation(s)

Clausthal University of Technology
University of Göttingen

Type

Article

Journal

Bioorganic and Medicinal Chemistry

Volume

8

Pages

2347-2354

No. of pages

8

ISSN

0968-0896

Publication date

31.08.2000

Publication status

Published

Peer reviewed

Yes

ASJC Scopus subject areas

Biochemistry, Molecular Medicine, Molecular Biology, Pharmaceutical Science, Drug Discovery, Clinical Biochemistry, Organic Chemistry

Electronic version(s)

https://doi.org/10.1016/S0968-0896(00)00166-8 (Access: Unknown)