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

The synthesis of novel aquayamycin-derived angucycline antibiotics 13a d ha s been achieved. Glycosylation of aquayamycin (6) using 2-selenoglycosyl ac etate 7 as glycosyl donor proceeded in excellent yield but attempts to redu ctively remove the selenyl group led to rearrangement or further aromatizat ion of the aglycon. As a consequence of these results, it became possible t o prepare urdamycinone B (10) starting from aquayamycin (6). Tn addition, s ilyl protected D-olivals 12a,b were attached to the C-glycoside domain of a quayamycin (6) under protic conditions. As expected, the hydroxy and phenol groups of the benz[a]anthracene framework of 6 did not react under the gly cosylation conditions employed. Stepwise removal of the silyl protecting gr oup starting with tetrabutyl ammonium fluoride followed by use of the HF/py ridine complex suppressed a possible rearrangement of the aglycon and succe ssfully terminated the sequence. The new angucycline-antibiotics 13a and 13 b are some of the most potent xanthine oxidase inhibitors known and show cy totoxic activity with ED50-values in the range of 12.6-2.9 x 10(-6) M (C) 2 000 Elsevier Science Ltd. All rights reserved.