Synthesis of N-Substituted 3-Aminomethylidenetetramic Acids

Abstract

(S)-3-(Dimethylamino)methylidene-5-benzyltetramic acid derivatives 4a and 4b were prepared in three steps from N-protected (S)-3-phenylalanines 1a and 1b, respectively. Similarly, N-[N-(benzyloxycarbonyl)glycyl]glycine (1c) was transformed into the enaminone 4c. Acid-catalysed coupling of enaminones 4a-c with aliphatic, aromatic, and heteroaromatic primary amines 5-34 afforded the corresponding N(3′)-substituted 3-aminomethylidenetetramic acid derivatives 35-64 in 29-96% yields.

amines - chiral pool - coupling - heterocycles - enami­nones

References

<A NAME="RT07105SS-1A">1a</A> Gossauer A. Prog. Chem. Org. Nat. Prod.  2003,  86:  1 

<A NAME="RT07105SS-1B">1b</A> Ghisalberti EL. Bioactive Tetramic Acid Metabolites, In Studies in Natural Products Chemistry, Bioactive Natural Products Part 1   Vol. 28:  . Elsevier; Amsterdam: 2003.  p.109 

<A NAME="RT07105SS-1C">1c</A> Royles BJL. Chem. Rev.  1995,  95:  1981 

<A NAME="RT07105SS-1D">1d</A> Shimshock SJ. DeShong P. Synthesis of the Tetramic Acid Antibiotics, In Studies in Natural Products Chemistry, Stereoselective Synthesis, Part 1   Vol. 14:  . Basha FZ. Elsevier; Amsterdam: 1994.  p.97 

<A NAME="RT07105SS-1E">1e</A> Henning H.-G. Gelbin A. Adv. Heterocycl. Chem.  1993,  57:  139 

<A NAME="RT07105SS-2A">2a</A> Rosset T. Sankhala RH. Stickings CE. Taylor MEU. Thomas R. Biochem. J.  1957,  67:  390 

<A NAME="RT07105SS-2B">2b</A> Lebrun MH. Dutfoy F. Gaudemer F. Kunesch G. Gaudemer A. Phytochemistry  1990,  29:  3777 

<A NAME="RT07105SS-2C">2c</A> Nukina M. Saito T. Biosci. Biotechnol. Biochem.  1992,  56:  1314 

<A NAME="RT07105SS-3A">3a</A> Burmeister HR. Bennet GA. Vesonder RF. Heseltine CW. Antimicrob. Agents Chemother.  1974,  5:  634 

<A NAME="RT07105SS-3B">3b</A> Vesonder RF. Tjarks LW. Rohwedder WK. Burmeister HR. Laugal JA. J. Antibiot.  1979,  32:  759 

<A NAME="RT07105SS-4A">4a</A> Holzapfel CW. Tetrahedron  1968,  24:  2101 

<A NAME="RT07105SS-4B">4b</A> Kozikowski AP. Greco MN. Springer JP. J. Am. Chem. Soc.  1984,  106:  6873 

<A NAME="RT07105SS-4C">4c</A> Muratake H. Natsume M. Heterocycles  1985,  23:  1111 

<A NAME="RT07105SS-5A">5a</A> Nowak A. Steffan B. Liebigs Ann./Recl.  1997,  1817 

<A NAME="RT07105SS-5B">5b</A> Nowak A. Steffan B. Angew. Chem. Int. Ed.  1998,  37:  3139 

<A NAME="RT07105SS-5C">5c</A> Dixon DJ. Ley SV. Longbottom DA. J. Chem. Soc., Perkin Trans. 1  1999,  2231 

For recent reviews, see:

<A NAME="RT07105SS-6A">6a</A> Stanovnik B. J. Heterocycl. Chem.  1999,  36:  1581 

<A NAME="RT07105SS-6B">6b</A> Stanovnik B. Svete J. Synlett  2000,  1077 

<A NAME="RT07105SS-6C">6c</A> Stanovnik B. Svete J. Targets Heterocycl. Syst.  2000,  4:  105 

<A NAME="RT07105SS-6D">6d</A> Svete J. J. Heterocycl. Chem.  2002,  39:  437 

<A NAME="RT07105SS-6E">6e</A> Svete J. Monatsh. Chem.  2004,  135:  629 

<A NAME="RT07105SS-6F">6f</A> Stanovnik B. Svete J. Chem. Rev.  2004,  104:  2433 

<A NAME="RT07105SS-6G">6g</A> Svete J. J. Heterocycl. Chem.  2005,  42:  361 

<A NAME="RT07105SS-6H">6h</A> Stanovnik B. Svete J. Mini-Rev. Org. Chem.  2005,  2:  211 

<A NAME="RT07105SS-7A">7a</A> Pirc S. Bevk D. Golič Grdadolnik S. Svete J. Arkivoc  2003,  xiv:  37 ; www.arkat-usa.org

<A NAME="RT07105SS-7B">7b</A> Westman J. Lundin R. Synthesis  2003,  1025 

<A NAME="RT07105SS-7C">7c</A> Čebaek P. Wagger J. Bevk D. Jakše R. Svete J. Stanovnik B. J. Comb. Chem.  2004,  6:  356 

<A NAME="RT07105SS-7D">7d</A> Čebaek P. Bevk D. Pirc S. Stanovnik B. Svete J. J. Comb. Chem.,  in press 

<A NAME="RT07105SS-8A">8a</A> Groelj U. Bevk D. Jakše R. Meden A. Rečnik S. Stanovnik B. Svete J. Synthesis  2005,  1087 

<A NAME="RT07105SS-8B">8b</A> Groelj U. Bevk D. Jakše R. Rečnik S. Meden A. Stanovnik B. Svete J. Tetrahedron  2005,  61:  3991 

<A NAME="RT07105SS-8C">8c</A> Groelj U. Bevk D. Jakše R. Meden A. Stanovnik B. Svete J. Tetrahedron: Asymmetry  2005,  16:  2187 

<A NAME="RT07105SS-8D">8d</A> Groelj U. Bevk D. Jakše R. Meden A. Pirc S. Rečnik S. Stanovnik B. Svete J. Tetrahedron: Asymmetry  2004,  15:  2367 

<A NAME="RT07105SS-8E">8e</A> Groelj U. Rečnik S. Svete J. Meden A. Stanovnik B. Tetrahedron: Asymmetry  2002,  13:  821 

<A NAME="RT07105SS-9A">9a</A> Courcambeck J. Bihel F. De Michelis C. Quéléver G. Kraus JL. J. Chem. Soc., Perkin Trans. 1  2001,  1421 

<A NAME="RT07105SS-9B">9b</A> Ma D. Ma J. Ding W. Dai L. Tetrahedron: Asymmetry  1996,  7:  2365 

<A NAME="RT07105SS-9C">9c</A> Jouin P. Castro B. Nisato D. J. Chem. Soc., Perkin Trans. 1  1987,  1177 

<A NAME="RT07105SS-9D">9d</A> Hamilakis S. Kontonassios D. Sandris C. J. Heterocycl. Chem.  1996,  33:  825 

<A NAME="RT07105SS-9E">9e</A> Li B. Franck RW. Bioorg. Med. Chem. Lett.  1999,  9:  2629 

<A NAME="RT07105SS-9F">9f</A> Liu Z. Ruan X. Huang X. Bioorg. Med. Chem. Lett.  2003,  9:  2505 

<A NAME="RT07105SS-10A">10a</A> Titman JJ. Foote J. Jarvis J. Keeler J. Neuhaus D. J. Chem. Soc., Chem. Commun.  1991,  419 

<A NAME="RT07105SS-10B">10b</A> Ando T. Koseki N. Toia RF. Casida JE. Magn. Res. Chem.  1993,  31:  90 

<A NAME="RT07105SS-10C">10c</A> Fischer P. Schweizer E. Langner J. Schmidt U. Magn. Res. Chem.  1994,  32:  567 

<A NAME="RT07105SS-11A">11a</A> Golič Grdadolnik S. Stanovnik B. Magn. Res. Chem.  1997,  35:  482 

<A NAME="RT07105SS-11B">11b</A> kof M. Svete J. Stanovnik B. Golič L. Golič-Grdadolnik S. Selič L. Helv. Chim. Acta  1998,  81:  2332 

<A NAME="RT07105SS-11C">11c</A> Ba J. Rečnik S. Svete J. Golič Grdadolnik S. Stanovnik B. Arkivoc  2001,  ii:  61 ; www.arkat-usa.org

<A NAME="RT07105SS-11D">11d</A> Bevk D. Kmetič M. Rečnik S. Svete J. Golič L. Golobič A. Stanovnik B. Chem. Heterocycl. Comp.  2001,  1651 

<A NAME="RT07105SS-11E">11e</A> Jakše R. Rečnik S. Svete J. Golobič A. Golič L. Stanovnik B. Tetrahedron  2001,  57:  8395 

<A NAME="RT07105SS-11F">11f</A> Jakše R. Kroelj V. Rečnik S. Sorak G. Svete J. Stanovnik B. Golič Grdadolnik S. Z. Naturforsch., B: Chem. Sci.  2002,  57:  453 

<A NAME="RT07105SS-11G">11g</A> Pirc S. Rečnik S. kof M. Svete J. Golič L. Meden A. Stanovnik B. J. Heterocycl. Chem.  2002,  39:  411 

<A NAME="RT07105SS-12">12</A> Nolte MJ. Steyn PS. Wessels PL. J. Chem. Soc., Perkin Trans. 1  1980,  1057 

<A NAME="RT07105SS-13">13</A> Bartholomew D. 1,3,5-Triazines, In Comprehensive Heterocyclic Chemistry II   Vol. 6:  Katritzky AR. Rees CW. Scriven EFV. Elsevier; Oxford: 1996.  p.575 

<A NAME="RT07105SS-14">14</A> Carter HE. Frank RL. Johnston HW. Org. Synth. Coll. Vol. III   Wiley; New York: 1955.  p.167 

<A NAME="RT07105SS-15">15</A> Altomare A. Burla MC. Camalli M. Dascarano G. Giacovazzo C. Guagliardi A. Polidori G. J. Appl. Cryst.  1994,  27:  435 

<A NAME="RT07105SS-16">16</A> Hall SR. King GSD. Stewart JM. The Xtal3.4 User’s Manual   University of Western Australia; Lamb, Perth: 1995. 

<A NAME="RT07105SS-17">17</A> Johnson CK. ORTEPII, Report ORNL-5138   Oak Ridge National Laboratory; Tennessee: 1976. 

<A NAME="RT07105SS-18">18</A>

The final atomic and geometrical parameters, crystal data and details concerning data collection and refinement for both compounds have been deposited with the Cambridge Crystallographic Data Centre as supplementary material with the deposition numbers: CCDC 272155 & 272156, respectively. These data can be obtained, free of charge via http://www.ccdc.cam.ac.uk/conts/retrieving.html.