Synthesis of pacidamycin analogues via an Ugi-multicomponent reaction.
The second-generation synthesis of 3'-hydroxypacidamycin D (2) has been accomplished via an Ugi-four component reaction at a late stage of the synthesis. This approach provided ready access to a range of analogues including diastereomers of the diaminobutylic acid residue and hybrid-type analogues of mureidomycins. Biological evaluations of these analogues indicated that the stereochemistry at the diaminobutylic acid residue has a crucial impact on both the MraY biochemical inhibition and whole-cell antibacterial activity.
Shionogi Innovation Center for Drug Discovery, Shionogi & Co., Ltd, Kita-21, Nishi-11, Kita-ku, Sapporo 001-0021, Japan.
Kazuya
K
Okamoto
Masahiro
M
Sakagami
Fei
F
Feng
Fumiyo
F
Takahashi
Kouichi
K
Uotani
Hiroko
H
Togame
Hiroshi
H
Takemoto
Satoshi
S
Ichikawa
Akira
A
Matsuda
D000447:Aldehydes / Q000737:chemistry; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D006900:Hydroxylation; D015394:Molecular Structure; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000494:pharmacology; D011549:Pseudomonas / Q000187:drug effects; D011741:Pyrimidine Nucleosides / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000447:Aldehydes; D000900:Anti-Bacterial Agents; D009842:Oligopeptides; D011741:Pyrimidine Nucleosides