Semisynthetic epsilon-isorhodomycins: their synthesis using glycals and their structure-activity relationship.
Syntheses and structure-activity relationships of 7-O-(3-amino-2,3,6-trideoxy-a-L-lyxo- (18), -L-arabino- (20) and -L-ribo- hexopyranosyl)-epsilon-isorhodomycins (25) and their 3'-dimethylamino derivatives 22, 23 and 26 are described. Condensation (trimethylsilyl triflate, molecular sieves 4 A, 10:1 dichloromethane-acetone, -15 degrees) of epsilon-isorhodomycinone (epsilon-isoRMN, 6) with 1,5-anhydro-4-O-p-nitrobenzoyl-3-trifluoroacetamido-L-lyxo- (5) -L-arabino- (9) or -L-ribo-hex-l-enitols (10) afforded mainly the 7-O-a-glycosyl-epsilon-isoRMNs 7, 11, and 12. Similar glycosylation of 6 with 1,5-anhydro-3-azido-4-O-p-nitrobenzoyl-2,3,6-trideoxy-L-arabino-hex-1-++ +enitol (15) yielded a-glycoside 16. Removal (M NaOH) of the p-nitrobenzoyl and trifluoroacetyl groups from 7, 11, and 12 gave the 7-O-(3-amino-2,3,6-trideoxy-a-L-hexopyranosyl)-epsilon-isoRMNs 18, 20, and 25. Reductive alkylation (CH2O, NaCNBH3) of these products afforded the 3'-N,N-dimethyl analogues 22, 23, and 26. The cytotoxic effect (IC50) of the semisynthetic epsilon-isorhodomycins was tested in vitro in leukemia cell line L1210.
Kolar
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C
Research Laboratories of Behringwerke AG, Marburg, F.R.G.
Dehmel
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Kraemer
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HP
D000818:Animals; D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic / Q000138:chemical synthesis*; D002240:Carbohydrate Sequence; D006031:Glycosylation; D008745:Methylation; D008969:Molecular Sequence Data; D015394:Molecular Structure; D010084:Oxidation-Reduction; D013329:Structure-Activity Relationship; D014410:Tumor Stem Cell Assay
D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic; C066033:7-O-(3-amino-2,3,6-trideoxy-alpha-hexopyranosyl)-epsilon-isorhodomycinone