Details
| Original language | English |
|---|---|
| Pages (from-to) | 2347-2354 |
| Number of pages | 8 |
| Journal | Bioorganic and Medicinal Chemistry |
| Volume | 8 |
| Issue number | 9 |
| Publication status | Published - 31 Aug 2000 |
| Externally published | Yes |
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.
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Biochemistry
- Biochemistry, Genetics and Molecular Biology(all)
- Molecular Medicine
- Biochemistry, Genetics and Molecular Biology(all)
- Molecular Biology
- Pharmacology, Toxicology and Pharmaceutics(all)
- Pharmaceutical Science
- Pharmacology, Toxicology and Pharmaceutics(all)
- Drug Discovery
- Biochemistry, Genetics and Molecular Biology(all)
- Clinical Biochemistry
- Chemistry(all)
- Organic Chemistry
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In: Bioorganic and Medicinal Chemistry, Vol. 8, No. 9, 31.08.2000, p. 2347-2354.
Research output: Contribution to journal › Article › Research › peer review
}
TY - JOUR
T1 - Syntheses and biological evaluation of new glyco-modified angucyclin-antibiotics
AU - Kirschning, Andreas
AU - Chen, Guang Wu
AU - Dräger, Gerald
AU - Schuberth, Ingrid
AU - Tietze, Lutz F.
N1 - Funding information: This work was supported by the Deutsche Forschungsgemeinschaft (SFB 416) and the Fonds der Chemischen Industrie (scholarship for G. D.). We wish to thank I. Sattler, A. Härtl, H.-M. Dahse, U. Möllmann, M. Schmidtke and R. Thiericke (Hans-Knöll-Institut, Jena, Germany) for biological testing. We thank AnalytiCon AG (Potsdam, Germany) for providing technical HPLC assistance. We are indebted to J. Rohr (Charleston, SC, USA) for a donation of Streptomyces fradiae .
PY - 2000/8/31
Y1 - 2000/8/31
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0033898083&partnerID=8YFLogxK
U2 - 10.1016/S0968-0896(00)00166-8
DO - 10.1016/S0968-0896(00)00166-8
M3 - Article
C2 - 11026547
AN - SCOPUS:0033898083
VL - 8
SP - 2347
EP - 2354
JO - Bioorganic and Medicinal Chemistry
JF - Bioorganic and Medicinal Chemistry
SN - 0968-0896
IS - 9
ER -