Synthesis of C-Protected 2,2-Dideutero β³-Amino Acids

Abstract

A simple three-step procedure for the preparation of C-protected 2,2-²H-β³-amino acids has been developed starting from the natural α-amino acids. Our synthetic path is based on the homologation reaction of α-amino acids through the formation of dideuterated alcohol intermediates obtained by heavy isotope reduction (NaBD₄) of the carboxylic function.

β³-amino acids - deuterated amino acids - isotopically labeled compounds

References

<A NAME="RZ16406SS-1">1</A> Lelais G. Seebach D. Biopolymers (Peptide Science)  2004,  76:  206 

<A NAME="RZ16406SS-2A">2a</A> Shinagawa S. Kanamaru T. Harada S. Asai M. Okazaki H. J. Med. Chem.  1987,  30:  1458 

<A NAME="RZ16406SS-2B">2b</A> Kanamaru T. Shinagawa S. Asai M. Okazaki H. Sugiyama Y. Fujita T. Iwatsuka H. Yoneda M. Life Sci.  1985,  37:  217 

<A NAME="RZ16406SS-3">3</A> Enantioselective Synthesis of β-Amino Acids   Juaristi E. Wiley-VCH; New York: 1997. 

<A NAME="RZ16406SS-4A">4a</A> von Nussbaum F. Spiteller P. Rüth M. Steglich W. Wanner G. Gamblin B. Stievano L. Wagner FE. Angew. Chem. Int. Ed.  1998,  37:  3292 

<A NAME="RZ16406SS-4B">4b</A> Spiteller P. Rüth M. von Nussbaum F. Steglich W. Angew. Chem. Int. Ed.  2000,  39:  2754 

<A NAME="RZ16406SS-5">5</A> Steer DL. Lew RA. Perlmutter P. Smith AI. Aguilar M.-I. Curr. Med. Chem.  2002,  9:  811 

<A NAME="RZ16406SS-6A">6a</A> Gademann K. Kimmerlin T. Hoyer D. Seebach D. J. Med. Chem.  2001,  44:  2460 

<A NAME="RZ16406SS-6B">6b</A> Nunn C. Rueping M. Langenegger D. Schuepbach E. Kimmerlin T. Micuch P. Hurth K. Seebach D. Hoyer D. Naunyn- Schmiedeberg’s Arch. Pharmacol.  2003,  367:  95 

<A NAME="RZ16406SS-7A">7a</A> Wiegand H. Wirz B. Schweitzer A. Camenisch GP. Rodriguez Perez MI. Gross G. Woessner R. Voges R. Arvidsson PI. Frakenpohl J. Seebach D. Biopharm. Drug Dispos.  2002,  23:  251 

<A NAME="RZ16406SS-7B">7b</A> Lind R. Greenhow D. Perry S. Kimmerlin T. Seebach D. Chem. Biodiv.  2004,  1:  1391 

<A NAME="RZ16406SS-7C">7c</A> Hook DF. Gessier F. Noti C. Kast P. Seebach D. ChemBioChem  2004,  5:  691 

<A NAME="RZ16406SS-8A">8a</A> Wiegand H. Wirz B. Schweitzer A. Gross G. Rodriguez Perez MI. Andres H. Kimmerlin T. Rueping M. Seebach D. Chem. Biodiv.  2004,  1:  1812 

<A NAME="RZ16406SS-8B">8b</A> Frackenpohl J. Arvidsson PI. Schreiber JV. Seebach D. ChemBioChem  2001,  2:  445 

<A NAME="RZ16406SS-9A">9a</A> Kostiainen R. Kotiaho T. Kuuranne T. Auriola S. J. Mass Spectrom.  2003,  38:  357 

<A NAME="RZ16406SS-9B">9b</A> Taylor EW. Jia W. Bush M. Dollinger GD. Anal. Chem.  2002,  74:  3232 

<A NAME="RZ16406SS-9C">9c</A> Ando S. Tanaka Y. Mass Spec. Rev.  2005,  24:  865 

<A NAME="RZ16406SS-10A">10a</A> Gygi SP. Rist B. Gerber SA. Turecek F. Gelb MH. Aebersold R. Nature Biotechnol.  1999,  17:  994 

<A NAME="RZ16406SS-10B">10b</A> Han DK. Eng J. Zhou H. Aebersold R. Nature Biotechnol.  2001,  19:  946 

<A NAME="RZ16406SS-11">11</A>

Unpublished results.

<A NAME="RZ16406SS-12">12</A>

β-Amino acids can be subdivided into β³, β², and β^2,3 amino acids, depending upon the position of the side chain(s) on the aminoalkanoic acid skeleton.

<A NAME="RZ16406SS-13">13</A> Capone S. Guaragna A. Palumbo G. Pedatella S. Tetrahedron  2005,  61:  6575 

<A NAME="RZ16406SS-14">14</A> Guaragna A. De Nisco M. D’Alonzo D. Pedatella S. Palumbo G. Synthesis  2006,  305 

<A NAME="RZ16406SS-15">15</A> Dewry DH. Coe DM. Poon S. Med. Res. Rev.  1999,  19:  97 

<A NAME="RZ16406SS-16">16</A>

Ph₃P-iodine complex showed the same reactivity of the polymer bound/iodine complex towards all the tested amino acids.