Stereoselective Synthesis of (2R)-6-Benzyloxycarbonylamino-2-tert-butoxycarbonylatninohex-4-ynoic Acid

Tetrahedron Asymmetry

Volumn 7, Issue 1, 1996, Pages 237-242

  Heerding, Dirk ^a   Bhatnagar, Pradip ^a   Hartmann, Michael ^b   Kremminger, Peter ^b   LoCastro, Stephen ^a  

^a GLAXOSMITHKLINE   (United Kingdom)

^b Nycomed Holdings AS   (Austria)

Author keywords

[No Author keywords available]

Indexed keywords

2,6 DIAMINOHEX 4 YNOIC ACID; AMINO ACID DERIVATIVE; UNCLASSIFIED DRUG;

ARTICLE; DRUG SYNTHESIS; PRIORITY JOURNAL; REACTION ANALYSIS; STEREOCHEMISTRY;

EID: 0030034964     PISSN: 09574166     EISSN: None     Source Type: Journal    
DOI: 10.1016/0957-4166(95)00441-6     Document Type: Article

References (10)

1. (a) Sasaki, A. N.; Morgat, J. L.; Bricas, E. Pept., Proc. Eur. Pept. Symp., 16th 1981, 224.
2. (b) Sasaki, A. N.; Bricas, E. Tetrahedron Lett. 1980, 21(44), 4263.
3. (c) Jansen, A. C. A.; Weastink, R. J. M.; Kerling, K. E. T.; Havinga, E. Red. Trav. Chim. Pays-Bas 1969, 88(8), 819.
4. A similar strategy has been employed to selectively protect the 6-amino group of lysine. See Schwzer, R.; Rittel, W. Helv. Chim. Acta 1961, 44, 159.
5. Schöllkopf, U.; Neubauer, H. -J. Synthesis 1982, 861 and references cited therein.
6. 4 from Aldrich or Fluka gave variable low yields of the desired compound. It was also crucial to quench the reaction by pouring it into a phosphate buffer at pH 7.2 and not vice versa.
7. (a) Koziara, A. J. Chem. Res. (S) 1989, 296;
8. (b) Koziara, A.; Osowska-Pacewicka, K.; Zawadzki, S.; Zwierzak, A. Synthesis 1985, 202.
9. (a) The enantiomeric excess of 8 was determined by the methodof Kinashita. The protecting groups of 8 were removed by acid hydrolysis and the corresponding diamino acid was derivatized with 2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl isothiocyanate. The diamino acid corresponsing to the enantiomer of 8 was also derivatized with 2,3,4,6-tetra-Oacetyl-β-D-glucopyranosyl isothiocyanate. Reverse phase HPLC analysis of the two diastereomeric thioureas revealed that only the desired antipode was observed within the limits of detection of our HPLC system.
10. (b) Kinashita, T.; Kasahara, Y.; Nimura, N. J. Chromatography 1981, 210, 77.