Total synthesis of novel antibiotics pyloricidin A, B and C and their application in the study of pyloricidin derivatives.
The novel natural antibiotics pyloricidin A, B and C, which possess potent and highly selective anti-Helicobacter pylori activity, were synthesized from D-galactosamine as a chiral template for the common (2S,3R,4R,5S)-5-amino-2,3,4,6-tetrahydroxyhexanoic acid moiety. The synthetic strategy, using 2-amino-2-deoxyuronic acid derivatives as key intermediates, was also useful to prepare a series of derivatives modified at the beta-D-phenylalanine and with altered stereochemistry on the 5-amino-2,3,4,6-tetrahydroxyhexanoic acid moiety. From the drastic decrease of their anti-H. pylori activity, it was clear that the beta-D-phenylalanine part and the stereochemistry of the 5-amino-2,3,4,6-tetrahydroxyhexanoic acid moiety were significant for the activity.
Hasuoka
Atsushi
A
Pharmaceutical Research Division, Takeda Chemical Industries, Ltd, Osaka, Japan. Hasuoka_Atsushi@takeda.co.jp
Nishikimi
Yuji
Y
Nakayama
Yutaka
Y
Kamiyama
Keiji
K
Nakao
Masafumi
M
Miyagawa
Ken-ichiro
K
Nishimura
Osamu
O
Fujino
Masahiko
M
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D016480:Helicobacter pylori / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents