Synthetic Aromatic Amino Acids from a Negishi Cross-Coupling Reaction

Abstract

An N,O-protected, iodinated bishomoalanine derivative, safely available from glutamic acid, reacts with aryl halides in a Negishi reaction in high yields. From the coupling product, Fmoc-protected amino acids with aromatic and heteroaromatic side chains were generated in high yields by racemization-free procedures. These monomers could be used for solid-phase peptide synthesis.

amino alcohols - chiral pool - nickel catalyst - RNA ligand - zinc organyls

References

<A NAME="RT12409SS-1">1</A> Chow CS. Bogdan FM. Chem. Rev.  1997,  97:  1489 

<A NAME="RT12409SS-2">2</A> Ludwig V. Krebs A. Stoll M. Dietrich U. Ferner J. Schwalbe H. Scheffer U. Dürner G. Göbel MW. ChemBioChem  2007,  8:  1850 

For Tat-TAR inhibition by peptides, see:

<A NAME="RT12409SS-3A">3a</A> Hamy F. Felder ER. Heizmann G. Lazdins J. Aboul-ela F. Varani G. Karns J. Klimkait T. Proc. Natl. Acad. Sci. U.S.A.  1997,  94:  3548 

<A NAME="RT12409SS-3B">3b</A> Hwang S. Tamilarasu N. Ryan K. Huq I. Richter S. Still WC. Rana TM. Proc. Natl. Acad. Sci. U.S.A.  1999,  96:  12997 

<A NAME="RT12409SS-3C">3c</A> Hwang S. Tamilarasu N. Kibler K. Cao H. Ali A. Ping Y.-H. Jeang K.-T. Rana TM. J. Biol. Chem.  2003,  278:  39092 

<A NAME="RT12409SS-3D">3d</A> Peytou V. Condom R. Patino N. Guedj R. Aubertin A.-M. Gelus N. Bailly C. Terreux R. Cabrol-Bass D. J. Med. Chem.  1999,  42:  4042 

<A NAME="RT12409SS-3E">3e</A> Athanassiou Z. Patora K. Dias RLA. Moehle K. Robinson JA. Varani G. Biochemistry  2007,  46:  741 

<A NAME="RT12409SS-3F">3f</A> Ferner J. Suhartono M. Breitung S. Jonker H. R. A. Hennig M. Wöhnert J. Göbel M. Schwalbe H. ChemBioChem  2009,  10:  1490 

<A NAME="RT12409SS-4A">4a</A> Taggi AE. Hafez AM. Lectka T. Acc. Chem. Res.  2003,  36:  10 

<A NAME="RT12409SS-4B">4b</A> Sardina FJ. Rapoport H. Chem. Rev.  1996,  96:  1825 

<A NAME="RT12409SS-4C">4c</A> Duthaler RO. Tetrahedron  1994,  50:  1539 

<A NAME="RT12409SS-4D">4d</A> Oppolzer W. Moretti R. Tetrahedron  1988,  44:  5541 

<A NAME="RT12409SS-4E">4e</A> Evans DA. Britton TC. Ellman JA. Dorow RL. J. Am. Chem. Soc.  1990,  112:  4011 

<A NAME="RT12409SS-4F">4f</A> Maruoka K. Ooi T. Chem. Rev.  2003,  103:  3013 

<A NAME="RT12409SS-5">5</A> Biotechnological synthesis of amino acids: Leuchtenberger W. Huthmacher K. Drauz K. Appl. Microbiol. Biotechnol.  2005,  69:  1 

<A NAME="RT12409SS-6">6</A> Krebs A. Ludwig V. Pfizer J. Dürner G. Göbel MW. Chem. Eur. J.  2004,  10:  544 

<A NAME="RT12409SS-7">7</A> Suhartono M. Weidlich M. Stein T. Karas M. Dürner G. Göbel MW. Eur. J. Org. Chem.  2008,  1608 

<A NAME="RT12409SS-8A">8a</A> Negishi E.-i. J. Organomet. Chem.  2002,  653:  34 

<A NAME="RT12409SS-8B">8b</A> Negishi E.-i. Handbook of Organopalladium Chemistry for Organic Synthesis   Wiley; New York: 2002. 

<A NAME="RT12409SS-9A">9a</A> Fraser JL. Jackson RFW. Porter B. Synlett  1994,  379 

<A NAME="RT12409SS-9B">9b</A> Dunn MJ. Jackson RFW. Pietruszka J. Turner D. J. Org. Chem.  1995,  60:  2210 

<A NAME="RT12409SS-9C">9c</A> Jackson RFW. Turner D. Block MH. J. Chem. Soc., Perkin Trans. 1  1997,  865 

<A NAME="RT12409SS-9D">9d</A> Jackson RFW. Moore RJ. Dexter CS. J. Org. Chem.  1998,  63:  7875 

<A NAME="RT12409SS-9E">9e</A> Deboves HJC. Montalbetti CAGN. Jackson RFW. J. Chem. Soc., Perkin Trans. 1  2001,  1876 

<A NAME="RT12409SS-9F">9f</A> Jackson RFW. Rilatt I. Murray PJ. Org. Biomol. Chem.  2004,  2:  110 

<A NAME="RT12409SS-9G">9g</A> Rilatt I. Caggiano L. Jackson RFW. Synlett  2005,  2701 

<A NAME="RT12409SS-9H">9h</A> Oswald CL. Carrillo-Marquez T. Caggiano L. Jackson RFW. Tetrahedron  2008,  64:  681 

<A NAME="RT12409SS-9I">9i</A> Kruppa M. Imperato G. König B. Tetrahedron  2006,  62:  1360 

<A NAME="RT12409SS-10">10</A> Ksander GM. de Jesus R. Yuan A. Ghai RD. McMartin AT. Bohacek R. J. Med. Chem.  1997,  40:  495 

<A NAME="RT12409SS-11">11</A> Jackson RFW. Perez-Gonzalez M. Org. Synth.  2005,  81:  77 

<A NAME="RT12409SS-12">12</A> Huo S. Org. Lett.  2003,  5:  423 

<A NAME="RT12409SS-13">13</A> Corey EJ. Schmidt G. Tetrahedron Lett.  1979,  20:  399 

<A NAME="RT12409SS-14">14</A> Li J, Tschaen DM, Song Z, and Zhao M. inventors; US  6150554. 

<A NAME="RT12409SS-15">15</A>

Due to the observed dynamic effects for the oxazolidine systems 4, 5, 7a-g, 16-18 an exact assignment was not possible. The existence of dynamic effects was exemplarily shown by a high temperature ^¹H NMR spectrum of compound 7a.