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Volumn 10, Issue 19, 2004, Pages 4718-4727

First total synthesis of hormaomycin, a naturally occurring depsipeptide with interesting biological activities

Author keywords

Natural products; Peptides; Protective groups; Synthetic methods; Total synthesis

Indexed keywords

AMINO ACIDS; BIODIVERSITY; CARBOXYLIC ACIDS; PROPYLENE; PROTEINS;

EID: 5444231828     PISSN: 09476539     EISSN: None     Source Type: Journal    
DOI: 10.1002/chem.200400249     Document Type: Article
Times cited : (25)

References (37)
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    • d) E Rossner, A Zeeck, W A. Konig, Angew Chem 1990, 102, 84-85, Angew Chem Int Ed Engl 1990, 29, 64-65
    • (1990) Angew Chem Int Ed Engl , vol.29 , pp. 64-65
  • 6
    • 5444226799 scopus 로고    scopus 로고
    • note
    • The previously unknown absolute configurations of the two nitrocyclopropylalanine residues as well as the 4-propenylproline moiety in 1 were established by a series of feeding experiments with the appropriate enantiomerically pure deuterium-labeled amino acids. It was additionally confirmed (in the case of 4-propenylproline) by a series of HPLC and HPLC/MS experiments
  • 8
    • 0029059341 scopus 로고
    • for a partial elucidation of the relative and absolute configurations of the two 3-(trans-2-nitrocyclopropyl)alanine moieties in hormaomycm 1, and the synthesis of enantiomerically pure mixtures of epimers of 3-(trans-2- nitrocyclopropyl)alanine, see also b) J Zindel, A de Meijere, J. Org Chem. 1995, 60, 2968-2973,
    • (1995) J Org Chem , vol.60 , pp. 2968-2973
    • Zindel, J.1    De Meijere, A.2
  • 13
    • 5444275477 scopus 로고    scopus 로고
    • note
    • The relatively low yield must be attributed to the noticeable susceptibility of the MOM ester to nucleophilic attack by the free amino group, especially when formation of a diketopiperazine ring is possible.
  • 14
    • 5444224507 scopus 로고    scopus 로고
    • note
    • The tetrapeptide 13b can also be used towards the synthesis of various analogues of 1
  • 16
    • 5444260938 scopus 로고
    • Although several N-MeZ-acylated glycines were prepared as early as in 1951 (cf. D M Channing, P B Turner, G. T. Young, Nature 1951, 167, 487-488), the authors considered that "these compounds appear to offer little advantage over the corresponding carbobenzyloxy compounds"; to the best of our knowledge, the application of p-methylbenzyloxycarbonyl group for peptide synthesis has never been considered again
    • (1951) Nature , vol.167 , pp. 487-488
    • Channing, D.M.1    Turner, P.B.2    Young, G.T.3
  • 17
    • 0028940130 scopus 로고
    • 2O (cf.. E. C. Roos, P Bernabe, H Hiemstra, W. N Speckamp, B Kaptein, W H J Bosten, J Org. Chem 1995, 60, 1733-1740) gave an inseparable mixture of unreacted and transprotected peptides in 34% yield, although with model peptides this technique worked pretty well (90-100% yield of the desirable product)
    • (1995) J Org Chem , vol.60 , pp. 1733-1740
    • Roos, E.C.1    Bernabe, P.2    Hiemstra, H.3    Speckamp, W.N.4    Kaptein, B.5    Bosten, W.H.J.6
  • 18
    • 5444274274 scopus 로고    scopus 로고
    • note
    • b) The ester bond between the (4-PE)Pro and a-Thr fragments may also be cleaved under strongly acidic (TFMSA in TFA, TMSOTf) conditions
  • 19
    • 5444271504 scopus 로고    scopus 로고
    • note
    • c) For the model dipeptide MeZ-Phe-Val-OMe
  • 20
    • 5444226167 scopus 로고    scopus 로고
    • note
    • d) From the secondary amino group of the (4-PE)Pro residue of the C-TMSE-protected acyclic precursor of the cyclic part of 1
  • 21
    • 5444253551 scopus 로고    scopus 로고
    • note
    • e) The rate of cleavage of the conventional Z-protective group was unacceptably slow even in the case of the model ester Z-Thr(OFmocPro)-OMe (incomplete deprotection with 20% thioanisole in TFA in 12 h at ambient temperature).
  • 22
    • 5444247613 scopus 로고    scopus 로고
    • note
    • f) The 3-methylbenzyloxycarbonyl and 3,5-dimethylbenzyloxycarbonyl groups were also tested, but turned out to be somewhat less suitable for application in this synthesis
  • 24
    • 5444221019 scopus 로고    scopus 로고
    • note
    • a) Chpca-(3-Ncp)Ala-OH was also synthesized, but turned out to be too unstable to be used for condensation with the deprotected 17.
  • 25
    • 5444237939 scopus 로고    scopus 로고
    • note
    • [9] reagent unexpectedly caused significant epimerization at the α-carbon of the (3-Ncp)Ala residue in the side chain and gave a separable mixture of epimers (MOM-1 and epi-MOM-1) in moderate yield
  • 27
    • 5444242334 scopus 로고    scopus 로고
    • note
    • a) The CD spectra were measured in methanol.
  • 28
    • 5444233941 scopus 로고    scopus 로고
    • note
    • b) It is noteworthy that both MOM-1 and epi-MOM-1 were equally active in this test and their activity was about 3 5 times lower than the activity of 1
  • 30
    • 5444233330 scopus 로고    scopus 로고
    • note
    • [1d] a mixture of all stereoisomers of 3-methylphenylalanine had been used as a reference). These latest results were in accordance with those obtained before.
  • 33
    • 5444249535 scopus 로고    scopus 로고
    • Patent US 5 580981, 1996
    • L. A. Carpino, Patent US 5 580981, 1996.
    • Carpino, L.A.1


* 이 정보는 Elsevier사의 SCOPUS DB에서 KISTI가 분석하여 추출한 것입니다.