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Volumn 350, Issue 11-12, 2008, Pages 1682-1688

Combined chemical-enzymatic assembly of aminoglycoside derivatives with N-1-AHB side chain

Author keywords

Aminoglycosides; Aminoglycosides toxicity; Biosynthesis of butirosin; Chemoenzymatic synthesis; Resistance to aminoglycosides; Stop codon readthrough

Indexed keywords


EID: 53849129237     PISSN: 16154150     EISSN: 15213897     Source Type: Journal    
DOI: 10.1002/adsc.200800229     Document Type: Article
Times cited : (8)

References (38)
  • 17
    • 53849085697 scopus 로고    scopus 로고
    • S. H. E. Swayze, J. Szychowski, S. S. Adhikari, K. Pachamuthu, X. Wang, M. T. Migawa, R. H. Griffey, (Isis Pharmaceuticals Inc), PCT WO2007064954, 2007.
    • h) S. H. E. Swayze, J. Szychowski, S. S. Adhikari, K. Pachamuthu, X. Wang, M. T. Migawa, R. H. Griffey, (Isis Pharmaceuticals Inc), PCT WO2007064954, 2007.
  • 33
    • 53849120440 scopus 로고    scopus 로고
    • L. Chen, M. Hainrichson, D. Bourdetsky, A. Mor, S. Yaron, T. Baasov, in preparation/revision.
    • L. Chen, M. Hainrichson, D. Bourdetsky, A. Mor, S. Yaron, T. Baasov, in preparation/revision.
  • 36
    • 53849090156 scopus 로고    scopus 로고
    • For the chemical installation of AHB at the N-1 position of NB30, we choose an approach that utilizes direct regioselective differentiation of the aminoglycoside amino groups by metal-mediated chelation[19] as illustrated in Scheme 2. Treatment of paromamine with Zn(OAc)2 and Boc2O afforded the selectively N-1-Boc-protected paromamine (32% isolated yield, which after azidation (TfN3) and regioselective acetylation (Ac2O at low temperature) gave the acceptor 17. Glycosidation of 17 with the trichloroacetimidiate donor under Lewis acid conditions furnished the desired pseudotrisaccharide 18. Compound 18 was then subjected to a sequential two-step procedure for the installation of the AHB moiety: treatment with TFA to remove the Boc group and the reaction of the resulted N-1 amine with (S)-2-hydroxy-4-azidobutyric acid (HOBT, DCC, Et3N) afforded the acyl migration product from the
    • 3N) afforded the acyl migration product from the 6 position to N-1 amine as a main product (75%). To avoid this limitation, 17 was first converted to the corresponding 6-hydroxy compound 19 in two successive steps (78%), which after the same two steps for the installation of AHB followed by treatment with methylamine and the Staudinger reaction furnished the desired product NB54 bearing the AHB moiety at the N-1 position.


* 이 정보는 Elsevier사의 SCOPUS DB에서 KISTI가 분석하여 추출한 것입니다.