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

verfasst von

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.

Externe Organisation(en)

Technische Universität Clausthal
Georg-August-Universität Göttingen

Typ

Artikel

Journal

Bioorganic and Medicinal Chemistry

Band

8

Seiten

2347-2354

Anzahl der Seiten

8

ISSN

0968-0896

Publikationsdatum

31.08.2000

Publikationsstatus

Veröffentlicht

Peer-reviewed

Ja

ASJC Scopus Sachgebiete

Biochemie, Molekularmedizin, Molekularbiologie, Pharmazeutische Wissenschaften, Wirkstoffforschung, Klinische Biochemie, Organische Chemie

Elektronische Version(en)

https://doi.org/10.1016/S0968-0896(00)00166-8 (Zugang: Unbekannt)