Synthesis of N-alkyl-(α-aminoalkyl)phosphine oxides and phosphonic esters as potential HIV-protease inhibitors, starting from α-aminoacids

Synlett

Volumn , Issue 5, 2000, Pages 698-700

  Alonso, Edgar ^a   Alonso, Eduardo ^a   Solis, Ana ^b   Del Pozo, Carlos ^a  

^a UNIVERSITY OF OVIEDO   (Spain)

^b Química ID Asturias SL ^*  (Spain)

Author keywords

aminoacids; aminophosphonic acids; Azomethine asymmetric addition; HIV protease inhibitors; Peptide mimics

Indexed keywords

ALPHA AMINO ACID; PHOSPHINE OXIDE DERIVATIVE; PHOSPHONIC ACID DERIVATIVE; PROTEINASE INHIBITOR;

ANTIVIRAL ACTIVITY; ARTICLE; DRUG STRUCTURE; DRUG SYNTHESIS; STRUCTURE ACTIVITY RELATION;

EID: 0034083373     PISSN: 09365214     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (20)

1. Perutz, M. in Protein Structure. New Approaches to Desease and Therapy, W. H. Freeman and Co. 1992, Chapter 5.
2. For comprehensive reviews, see: a) Kafarski, P.; Lejczak, B. Phosphorus, Sulfur Silicon Relat. Elem. 1991, 63, 193.
3. b) Bartlett, P. A.; Marlowe, C. K.; Giannousis, P.P.; Hanson, J. E. Cold Spring Harbor Sump. Quant. Biol. 1987, LII, 83.
4. Venturini, A.; López-Ortiz, F.; Alvarez, J. M.; González, J. J. Am. Chem. Soc. 1998, 720, 1110.
5. Rich, D. H.; Green, J.; Mihaly, V. T.; Marshall, G. R.; Kent, S. B. H. J. Med. Chem. 1990, 33, 1288.
6. Bartlett, P. A.; Lamden, L. A. Bioorganic Chem. 1986, 14, 356.
7. α-Aminophosphonic acids as antibiotics: Atherton, F. R., Hassall, C. H.; Lambert, R. W. J. Med. Chem. 1986, 29, 29. As pharmacological agents: Hasall, C. H. In Antibiotics; E. Eds.; F. E. Halm, Springer-Verlag: Berlin, 1983: Vol. VI, pp. 1-11. As enzyme inhibitors: Allen, M. C.; Fuhrer, W.; Tuck, B.; Wade, R.; Wood, J. M. J. Med. Chem. 1990, 33, 1288.
8. α-Aminophosphonic acids as antibiotics: Atherton, F. R., Hassall, C. H.; Lambert, R. W. J. Med. Chem. 1986, 29, 29. As pharmacological agents: Hasall, C. H. In Antibiotics; E. Eds.; F. E. Halm, Springer-Verlag: Berlin, 1983: Vol. VI, pp. 1-11. As enzyme inhibitors: Allen, M. C.; Fuhrer, W.; Tuck, B.; Wade, R.; Wood, J. M. J. Med. Chem. 1990, 33, 1288.
9. α-Aminophosphonic acids as antibiotics: Atherton, F. R., Hassall, C. H.; Lambert, R. W. J. Med. Chem. 1986, 29, 29. As pharmacological agents: Hasall, C. H. In Antibiotics; E. Eds.; F. E. Halm, Springer-Verlag: Berlin, 1983: Vol. VI, pp. 1-11. As enzyme inhibitors: Allen, M. C.; Fuhrer, W.; Tuck, B.; Wade, R.; Wood, J. M. J. Med. Chem. 1990, 33, 1288.
10. For a recent review, see: Nicaise, O. J.-C.; Denmark, S. E. J. Chem. Soc., Chem. Commun. 1996, 999.
11. Bodanszky, M.; Bodanszky, A. in The Practice of Peptide Synthesis, Springer-Verlag Berlin Heidelberg 1994, p. 30-31.
12. 3N (4.5 mmol) was added and the resultant solution was stirred for 20 min. After this period, molecular sieves and the corresponding aldehyde (3 mmol) were added and the reaction mixture was stirred overnight. Filtration through celite and elimination of solvents in vacuo afforded the desired imines 3 in nearly quantitative yields. These products were used without further purification.
13. 2PH as a phosphorus source. Unfortunately, only the products derived from the addition of the corresponding phosphide to the ester group were observed. The reaction seems to be very sensitive to steric requirements.
14. Asymmetric addition of carbon and phosphorus nucleophiles to the C=N function still has to meet success, even when the lure of a general synthesis of chiral amines by these approaches has stimulated much activity.
15. 3: C, 73.82; H, 5.76. Found: C, 73.54; H, 5.98.
16. Soroka, M.; Zygmunt, J. Synthesis 1988, 370.
17. 5: C, 62.98; H, 7.21. Found: C, 63.24; H, 6.98.
18. When anions derived from diethyl and dimethyl phosphite were used, no formation of the adducts 5 was observed.
19. Afarinkia, K.; Rees, C. W.; Cadogan, J. I. G. Tetrahedron 1990, 46, 7175.
20. b) Afarinkia, K.; Rees, C. W.; Cadogan, J. I. G. Synlett 1992, 3, 1224.