PMID- 21372526
OWN - NLM
STAT- MEDLINE
DCOM- 20110825
LR  - 20190724
IS  - 0031-6903 (Print)
IS  - 0031-6903 (Linking)
VI  - 131
IP  - 3
DP  - 2011 Mar
TI  - [Comprehensive synthetic study of muraymycins toward the development of novel 
      antibacterial agents].
PG  - 335-46
AB  - This review describes the synthesis and structure-activity relationship (SAR) 
      study of muraymycins (MRYs), which are potent antibacterial nucleoside 
      antibiotics. The key elements of our synthetic approach include the preparation 
      of L-epi-capreomycidine via a C-H amination reaction and a convergent assemblage 
      to construct of the framework of MRYs using Ugi four component reaction. With 
      this approach the first total synthesis of MRY D2 and its epimer, epi-MRY D2, 
      which does not have lipophilic substituents, has been accomplished. The fact that 
      MRY D2 and it's epimer did not show any antibacterial activity indicated the 
      lipophilic substituents of MRYs plays an important role in membrane-permeability. 
      Hence, MRY analogues with lipophilic substituents were designed and synthesized 
      simply by altering the aldehyde component in Ugi four-component assemblage. The 
      MRY analogues with lipophilic substituents exhibited improved antibacterial 
      activity against anti drug-resistant bacteria. It was also suggested that the 
      accessory urea-dipeptide motif might contribute to MraY inhibitory and 
      antibacterial activity. Our synthetic approach would effectively provide a 
      variety of MRY analogues and resultant SAR information brings us directions to 
      create further MRY analogues.
FAU - Tanino, Tetsuya
AU  - Tanino T
AD  - Graduate School of Life Science, Hokkaido University. 
      tetuya@mail.sci.hokudai.ac.jp
FAU - Ichikawa, Satoshi
AU  - Ichikawa S
FAU - Uotani, Koichi
AU  - Uotani K
FAU - Oyama, Hiroshi
AU  - Oyama H
FAU - Matsuda, Akira
AU  - Matsuda A
LA  - jpn
PT  - English Abstract
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - Japan
TA  - Yakugaku Zasshi
JT  - Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan
JID - 0413613
RN  - 0 (Anti-Bacterial Agents)
RN  - 0 (Nucleosides)
RN  - 0 (Peptides)
RN  - 0 (muraymycin D2)
SB  - IM
MH  - Anti-Bacterial Agents/*chemical synthesis/pharmacology
MH  - Bacteria/drug effects
MH  - *Drug Design
MH  - Drug Resistance, Bacterial
MH  - Nucleosides/*chemical synthesis/pharmacology
MH  - Peptides/*chemical synthesis/pharmacology
MH  - Structure-Activity Relationship
EDAT- 2011/03/05 06:00
MHDA- 2011/08/27 06:00
CRDT- 2011/03/05 06:00
PHST- 2011/03/05 06:00 [entrez]
PHST- 2011/03/05 06:00 [pubmed]
PHST- 2011/08/27 06:00 [medline]
AID - JST.JSTAGE/yakushi/131.335 [pii]
AID - 10.1248/yakushi.131.335 [doi]
PST - ppublish
SO  - Yakugaku Zasshi. 2011 Mar;131(3):335-46. doi: 10.1248/yakushi.131.335.