Download PDF
Synthesis 2011(24): 4023-4026  
DOI: 10.1055/s-0031-1289586
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Preparation of α-Hydroxy-β-Fmoc Amino Acids from N-Boc Amino Acids

Erik P. Johnsona, M. Patricia Hubiekia, Andrew P. Combsb, Christopher A. Teleha*b
a J-STAR Research Inc., 3001 Hadley Road, Unit 1-3, South Plainfield, NJ 07080, USA
b Bristol-Myers Squibb Pharmaceutical Co., Pharmaceutical Research Institute, Discovery Chemistry, P.O. Box 80336, Wilmington, DE 19880, USA
Fax: +1(215)5404611; e-Mail: cteleha@its.jnj.com;
Further Information

Publication History

Received 6 September 2011
Publication Date:
03 November 2011 (online)

    Permissions and Reprints All articles of this category

Abstract

A general method for the conversion of N-Boc amino acids­ into their homologated α-hydroxy-β-Fmoc amino acids is described. The protocol involved preparation of the amino aldehyde by reduction of the corresponding Weinreb amides, hydrocyanation, and hydrolysis of the nitrile group, followed by reprotection of the amino acid as the Fmoc derivative.

Key words

N-Boc amino acid - reduction - hydrocyanation - N-Fmoc amino acid

    References

  • 3 Han W. Hu Z. Jiang X. Decicco CP. Bioorg. Med. Chem. Lett.  2000,  10:  711 
    Google Scholar
  • 4 Tromp RA. Van de Hoeven M. Amore A. Brussee J. Overhand M. Van der Marel GA. Van der Gen A. Tetrahedron: Asymmetry  2001,  12:  1109 
    Google Scholar
  • 5 Harbeson SL. Abelleira SM. Akiyama A. Barrett R. Carroll RM. Straub JA. Tkacz JW. Wu C. Musso G. J. Med. Chem.  1994,  37:  2918 
    Google Scholar
  • 6 Boger DL. Colletti SL. Honda T. Menezes RF. J. Am. Chem. Soc.  1994,  116:  5607 
    Google Scholar
  • 7 Skiles JW. Miao C. Sorcek R. Jacober S. Mui PW. Chow G. Weldon SM. Possanza G. Skoog M. Keirns J. Letts G. Rosenthal AS. J. Med. Chem.  1992,  35:  4795 
    Google Scholar
  • 8 Saari WS. Fisher TE. Synthesis  1990,  453 
    Google Scholar
  • 9 Tietze LF. Burkhardt O. Synthesis  1994,  1331 
    Google Scholar
  • 10 Hamada Y. Shibata M. Sugiura T. Kato S. Shioiri T. J. Org. Chem.  1987,  52:  1252 
    Google Scholar
  • 11 For preparation of the Fmoc derivative, see: Myers AG. Kung DW. Zhong B. J. Am. Chem. Soc.  2000,  122:  3236 
    Google Scholar
  • 12 Veeresa G. Datta A. Tetrahedron Lett.  1998,  39:  3069 
    Google Scholar
  • 13 Greenlee WJ. Springer JP. Patchett A. J. Med. Chem.  1989,  32:  165 
    Google Scholar
  • 14 Mohan R. Chou Y.-L. Bihovsky R. Lumma WC. Erhardt PW. Shaw KJ. J. Med. Chem.  1991,  34:  2402 
    Google Scholar
  • 15 Iizuka K. Kamijo T. Harada H. Akahane K. Kubota T. Shimaoka I. Umeyama H. Kiso Y. Chem. Pharm. Bull.  1988,  36:  2278 
    Google Scholar
  • 16 Myers AG. Zhong B. Movassaghi M. Kung DW. Lanman BA. Kwon A. Tetrahedron Lett.  2000,  41:  1359 
    Google Scholar
  • 17 Tsuda M. Muraoka Y. Nagai M. Takeuchi T. Aoyagi T. J. Antibiot.  1996,  49:  287 
    Google Scholar
  • 19 Bursavich MG. Rich DH. J. Med. Chem.  2002,  45:  541 
    Google Scholar
1

New address: Incyte Corporation, Wilmington, DE, USA.

2

New address: Johnson and Johnson Pharmaceutical Research and Development, Welsh and McKean Roads, Spring House, PA, USA.

18

Personal communication: Dr. Dan Siesel, Albany Molecular Research Inc.