A Practical and Stereoconservative Synthesis of (R)-3-Amino-4-(trimethyl-ammonio)butanoate [(R)-Aminocarnitine], and Its Trimethylphosphonium and Simple Ammonium Analogues Starting from D-Aspartic Acid

European Journal of Organic Chemistry

Volumn , Issue 23, 2003, Pages 4501-4505

  Calvisi, Giuseppina ^a   Dell'Uomo, Natalina ^a   De Angelis, Francesco ^b   Dejas, Roberto ^a   Giannessi, Fabio ^a   Tinti, Maria Ornella ^a  

^a Dipartimento Ricerca Chimica   (Italy)

^b UNIVERSITY OF L'AQUILA   (Italy)

Author keywords

Amines; Betaines; CPT I Inhibitors; Lactones; Nucleophilic substitution

Indexed keywords

3 AMINO (4 TRIMETHYLPHOSPHONIO)BUTANOIC ACID; 3 AMINO 4 (TRIMETHYLAMMONIO)BUTANOATE; 3,4 DIAMINOBUTANOIC ACID; AMMONIUM DERIVATIVE; DEXTRO ASPARTIC ACID; EMERIAMINE; PHOSPHONIUM DERIVATIVE; TRIMETHYLPHOSPHONIUM; UNCLASSIFIED DRUG;

ARTICLE; DRUG STRUCTURE; DRUG SYNTHESIS; MOLECULE; OPTICS; REACTION ANALYSIS; SCALE UP; STEREOCHEMISTRY; STEREOSPECIFICITY; STRUCTURE ANALYSIS;

EID: 0345600807     PISSN: 1434193X     EISSN: None     Source Type: Journal    
DOI: 10.1002/ejoc.200300428     Document Type: Article

References (20)

1. [a] T. Kanamaru, S. Shinagawa, M. Asai, H. Okazaki, Y. Sugiyama, T. Fuyita, H. Iwatsuka, M. Yoneda, Life Sci. 1985, 37, 217-223.
2. [b] D.L. Jenkins, O.W. Griffith, J. Biol. Chem. 1985, 260, 14748-14755.
3. [c] W.C. Hulsmann, C. Schneydemberg, A.J. Verkley, Biochim. Biophys. Acta 1991, 1097, 263-269.
4. [d] P. Chiodi, F. Maccari, M.T. Ramacci, Biochim. Biophys. Acta 1992, 1127, 81-86.
5. [e] S. Shinagawa, T. Kanamaru, S. Harada, M. Asai, H. Okazaki, J. Med. Chem. 1987, 30, 1458-1463.
6. [f] T. Kanamaru, S. Shinagawa, M. Asai, (Takeda), WO 8401574 1984, Chem. Abstr. 1984, 101, 73104a.
7. [a] F. Giannessi, P. Chiodi, M. Marzi, P. Minetti, P. Pessotto, F. De Angelis, E. Tassoni, R. Conti, F. Giorgi, M. Mabilia, N. Dell'Uomo, S. Muck, M. O. Tinti, P. Carminati, A. Arduini, J. Med. Chem. 2001, 44, 2383-2386.
8. [b] F. Giannessi, M. Marzi, P. Minetti, M. O. Tinti, F. De Angelis, P. Chiodi, A. Arduini, (Sigma-Tau), WO99/59957 1999, Chem. Abstr. 1999, 131, 351673.
9. [a] D. Misiti, M. Santaniello, G. Zappia, Bioorg. Med. Chem. Lett. 1992, 2, 1029-1032;
10. [b] T. Kanamaru, S. Shinagawa, M. Asai, (Takeda) WO 8400539, 1984, Chem. Abstr. 1984, 101, 7642y.
11. [c] M.O. Tinti, D. Misiti, (Sigma-Tau) EP 287523, 1988, Chem. Abstr. 1989, 110, 94866b.
12. [d] G. Cardillo, M. Orena, M. Penna, S. Sandri, C. Tomasini, Synlett 1990, 543-544.
13. [e] M. O. Tinti, D. Misiti (Sigma-Tau), EP 402322, 1990, Chem. Abstr. 1991, 115, 72225t; see also ref. [1b, 1e, 1f]
14. R. Castagnani, F. De Angelis, E. De Fusco, F. Giannessi, D. Misiti, D. Meloni, M. O. Tinti, J. Org. Chem. 1995, 60, 8318-8319.
15. F. Giannessi, N. Dell'Uomo, M. O. Tinti, F. De Angelis (Sigma-Tau), WO 0102341 2001, Chem. Abstr 2001, 134, 85546.
16. [a] C. W. Jefford, J. McNulty, Helv. Chim. Acta 1994, 77, 2142-2146.
17. [b] C. W. Jefford, J. McNulty, L. Zhi-Hui, J. B. Wang, Helv. Chim. Acta 1996, 79, 1203-1216.
18. Isobutyl esters are prone to crystallize and less hygroscopic than the ethyl ester derivative. The ethyl ester of 6 has also been prepared: the advantage in this latter case is the possibility of using commercially available 30% trimethylamine in ethanol in the following step. The ethyl ester also gives (R)-aminocarnitine in the same yield and ee as the isobutyl derivative.
19. R. H. Buck, K. Krummen, J. Chromatogr 1987, 387, 255-265.
20. D. Misiti, M. Santaniello, G. Zappia, Synth. Commun. 1992, 22, 883-891.