Synthesis of 7'-(3-hydroxypropyl)fortimicin A and 6'-epifortimicin A.
1,10-Di-0-acetyl-2,3,4,6,7,8,9-heptadeoxy-2,6-bis(2, 4-dinitrophenylamino)-L-lyxo-decopyranose (7) and -D-ribo-decopyranose (8) have been prepared from methyl 2-acetamido-2,3,4,6-tetradeoxy-6-nitro-alpha-D-erythro-hexopyranoside via a nitro aldol reaction with 4-[(tetrahydropyranyl)oxy]butanal in the presence of cesium fluoride, and their configurations at C-6 have been established by conversion of the precursor of 8, namely, methyl 2,6-diacetamido-10-O-acetyl-2,3,4,6,7,8,9-heptadeoxy-alpha-D - ribo-decopyranoside, into the known methyl 2,6-diacetamido-2,3,4,6,7,8,9,10-octadeoxy-alpha-D-ribo-d ecopyranoside. The title fortimicin A derivatives, 7'-(3-hydroxypropyl)fortimicin A and 6'-epifortimicin A, have been synthesized by condensation of compound 7 and 8, respectively, with 2,5-di-O-benzoyl-1,4-bis[N-(methoxycarbonyl)]fortamine B, followed by deprotection and introduction of a glycyl group. Their antimicrobial activities have been found to be weak compared to that of fortimicin A.
Kanai
K
K
Department of Applied Chemistry, Faculty of Science and Technology, Keio University, Yokohama, Japan.
Nishigaki
J
J
Taki
T
T
Ogawa
S
S
Suami
T
T
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects; D007202:Indicators and Reagents; D008826:Microbial Sensitivity Tests; D009904:Optical Rotation; D013329:Structure-Activity Relationship
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D007202:Indicators and Reagents; C055013:7'-(3-hydroxypropyl)fortimicin A; C055014:6'-epifortimicin A