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DOI: 10.1055/s-0029-1218771
A Practical and Convenient Synthesis of the Protease Inhibitor Epibestatin
Publikationsverlauf
Publikationsdatum:
05. Mai 2010 (online)

Abstract
A convenient synthesis of the protease inhibitor epibestatin, a useful component in protease inhibition cocktails for use in proteomics research, is described. The synthesis sequence consists of seven steps, starting from phenylacetaldehyde, yielding enantiopure epibestatin in 8% overall yield. A regioselective Mitsunobu transformation of a diol is the key step in the sequence.
Key words
amino acids - asymmetric synthesis - osmium - dihydroxylation - Mitsunobu reaction
- 1a Aprotenine
is also known as Trasylol (Bayer). For a recent reference, see:
Diniz CM.Xavier LP.Santoro MM.Figueiredo AFS. Curr. Enzyme Inhib. 2009, 5: 163MissingFormLabel - 1b
Aoyagi T.Takeuchi T.Matsuzaki A.Kawamura K.Kondo S.Hamada M.Maeda K.Umezawa H. J. Antibiot. 1969, 22: 283MissingFormLabel - 1c
Umezawa H.Aoyagi T.Suda H.Hamada M.Takeuchi T. J. Antibiot. 1976, 29: 97MissingFormLabel - 1d
Umezawa H.Aoyagi T.Morishima H.Matsuzaki M.Hamada M.Takeuchi T. J. Antibiot. 1970, 23: 259MissingFormLabel - 1e
For general application information, see: Sigma technical bulletin on protease inhibition cocktails INHIB1.
MissingFormLabel - 1f For information on epibestatin
as peptidase inhibitor, see:
Rich DH.Moon BJ.Harbeson S. J. Med. Chem. 1984, 27: 417MissingFormLabel - 1g For the original description
of epibestatin, see:
Nishizawa R.Saino T. J. Med. Chem. 1977, 20: 510MissingFormLabel - 2a
Epibestatin is available in very limited quantities from Sigma, ordering number E0381.
MissingFormLabel - 2b
Lee JH.Kim JH.Lee BW.Seo WD.Yang MS.Park KH. Bull. Korean Chem. Soc. 2006, 27: 1211MissingFormLabel - 3
Ko S. J. Org. Chem. 2002, 67: 2689 - 4a
Wadsworth W.Emmons W. J. Am. Chem. Soc. 1961, 83: 1733MissingFormLabel - 4b
Claridge TDW.Davies SG.Lee JA.Nicholson RL.Roberts PM.Russell AJ.Smith AD.Toms SM. Org. Lett. 2008, 10: 5437MissingFormLabel - 5a
Jacobsen E.Marko I.Mungall W.Schroder G.Sharpless K. J. Am. Chem. Soc. 1988, 110: 1968MissingFormLabel - 5b
Sharpless KB.Amberg W.Bennani YL.Crispino GA.Hartung J.Jeong KS.Kwong HL.Morikawa K.Wang ZM.Xu DQ.Zhang XL. J. Org. Chem. 1992, 57: 2768MissingFormLabel - 6
Swamy KCK.Kumar NNB.Balaraman E.Kumar KVPP. Chem. Rev. 2009, 109: 2551 - 8 Compound 9 and
its enantiomer have been reported previously in literature. For
a recent synthesis, see:
Masaya K.Matsumoto J.Yukifumi N. Tetrahedron: Asymmetry 2002, 13: 1201 - 9
Montalbetti C.Falque V. Tetrahedron 2005, 61: 10827
References
The structural verification of 5 was based on the characteristic 2D NMR cross peaks (COSY, HMBC) after conversion of the azide functionality into the corresponding N-acetamide derivative.