A practical synthesis of protected β-homolysine

Tetrahedron Asymmetry

Volumn 11, Issue 10, 2000, Pages 2231-2237

  Baenziger, Markus ^a   Gobbi, Luca ^a   Riss, Bernard P ^a   Schaefer, Frank ^a   Vaupel, Andrea ^a  

^a NOVARTIS PHARMA AG   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

(ALPHA METHYLBENZYL)BENZYLAMIDE; 7 (TOSYLOXY)HEPT 2 ENOIC ACID TERT BUTYL ESTER; AMMONIA; BETA HOMOLYSINE; LYSINE DERIVATIVE; UNCLASSIFIED DRUG;

ARTICLE; CARBON NUCLEAR MAGNETIC RESONANCE; CHEMICAL REACTION; CONTROLLED STUDY; DRUG PURITY; DRUG SYNTHESIS; ENANTIOMER; MASS SPECTROMETRY; PRIORITY JOURNAL; PROTON NUCLEAR MAGNETIC RESONANCE; STEREOCHEMISTRY;

EID: 0034595783     PISSN: 09574166     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0957-4166(00)00173-7     Document Type: Article

References (30)

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6. A description of this synthesis will be submitted to publication. Also, for this strategy, see: Caputo, R.; Cassano, E.; Lomgobardo, L.; Palumbo, G. Tetrahedron 1995, 51(45), 12337-12350. For general references concerning β-amino acids, see: Enantioselective Synthesis of β-Amino Acids; Juaristi, E.; Wiley VCH: New York, 1997. Juaristi, E.; Quintana, D.; Escalante, J. Aldrichimica Acta 1994, 27(1), 3-11.
7. A description of this synthesis will be submitted to publication. Also, for this strategy, see: Caputo, R.; Cassano, E.; Lomgobardo, L.; Palumbo, G. Tetrahedron 1995, 51(45), 12337-12350. For general references concerning β-amino acids, see: Enantioselective Synthesis of β-Amino Acids; Juaristi, E.; Wiley VCH: New York, 1997. Juaristi, E.; Quintana, D.; Escalante, J. Aldrichimica Acta 1994, 27(1), 3-11.
8. A description of this synthesis will be submitted to publication. Also, for this strategy, see: Caputo, R.; Cassano, E.; Lomgobardo, L.; Palumbo, G. Tetrahedron 1995, 51(45), 12337-12350. For general references concerning β-amino acids, see: Enantioselective Synthesis of β-Amino Acids; Juaristi, E.; Wiley VCH: New York, 1997. Juaristi, E.; Quintana, D.; Escalante, J. Aldrichimica Acta 1994, 27(1), 3-11.
9. Davies, S. G.; Ichihara, O. Tetrahedron: Asymmetry 1991, 2(3), 183-186. Bunnage, M. E.; Davies, S. G.; Goodwin, C. J. J. Chem. Soc., Perkin Trans. 1 1993, 1375-1376. Davies, S. G.; Ichihara, O.; Walter, I. A. S. J. Chem. Soc., Perkin Trans. 1 1994, 1141-1147. Davies, S. G.; Walter, I. A. S. J. Chem. Soc., Perkin Trans. 1 1994, 1129-1139. Bunnage, M. E.; Davies, S. G.; Goodwin, C. J.; Ischihara, O. Tetrahedron 1994, 50, 3975-3986. Davies, S. G.; Bhalay, G. Tetrahedron: Asymmetry 1996, 7(6), 1595. Davies, S. G.; Ichihara, O. Tetrahedron: Asymmetry 1996, 7(7), 1919. Davies, S. G.; Smyth, G. D.; Chippindale, A. M. J. Chem. Soc., Perkin Trans. 1 1999, 3089.
10. Davies, S. G.; Ichihara, O. Tetrahedron: Asymmetry 1991, 2(3), 183-186. Bunnage, M. E.; Davies, S. G.; Goodwin, C. J. J. Chem. Soc., Perkin Trans. 1 1993, 1375-1376. Davies, S. G.; Ichihara, O.; Walter, I. A. S. J. Chem. Soc., Perkin Trans. 1 1994, 1141-1147. Davies, S. G.; Walter, I. A. S. J. Chem. Soc., Perkin Trans. 1 1994, 1129-1139. Bunnage, M. E.; Davies, S. G.; Goodwin, C. J.; Ischihara, O. Tetrahedron 1994, 50, 3975-3986. Davies, S. G.; Bhalay, G. Tetrahedron: Asymmetry 1996, 7(6), 1595. Davies, S. G.; Ichihara, O. Tetrahedron: Asymmetry 1996, 7(7), 1919. Davies, S. G.; Smyth, G. D.; Chippindale, A. M. J. Chem. Soc., Perkin Trans. 1 1999, 3089.
11. Davies, S. G.; Ichihara, O. Tetrahedron: Asymmetry 1991, 2(3), 183-186. Bunnage, M. E.; Davies, S. G.; Goodwin, C. J. J. Chem. Soc., Perkin Trans. 1 1993, 1375-1376. Davies, S. G.; Ichihara, O.; Walter, I. A. S. J. Chem. Soc., Perkin Trans. 1 1994, 1141-1147. Davies, S. G.; Walter, I. A. S. J. Chem. Soc., Perkin Trans. 1 1994, 1129-1139. Bunnage, M. E.; Davies, S. G.; Goodwin, C. J.; Ischihara, O. Tetrahedron 1994, 50, 3975-3986. Davies, S. G.; Bhalay, G. Tetrahedron: Asymmetry 1996, 7(6), 1595. Davies, S. G.; Ichihara, O. Tetrahedron: Asymmetry 1996, 7(7), 1919. Davies, S. G.; Smyth, G. D.; Chippindale, A. M. J. Chem. Soc., Perkin Trans. 1 1999, 3089.
12. Davies, S. G.; Ichihara, O. Tetrahedron: Asymmetry 1991, 2(3), 183-186. Bunnage, M. E.; Davies, S. G.; Goodwin, C. J. J. Chem. Soc., Perkin Trans. 1 1993, 1375-1376. Davies, S. G.; Ichihara, O.; Walter, I. A. S. J. Chem. Soc., Perkin Trans. 1 1994, 1141-1147. Davies, S. G.; Walter, I. A. S. J. Chem. Soc., Perkin Trans. 1 1994, 1129-1139. Bunnage, M. E.; Davies, S. G.; Goodwin, C. J.; Ischihara, O. Tetrahedron 1994, 50, 3975-3986. Davies, S. G.; Bhalay, G. Tetrahedron: Asymmetry 1996, 7(6), 1595. Davies, S. G.; Ichihara, O. Tetrahedron: Asymmetry 1996, 7(7), 1919. Davies, S. G.; Smyth, G. D.; Chippindale, A. M. J. Chem. Soc., Perkin Trans. 1 1999, 3089.
13. Davies, S. G.; Ichihara, O. Tetrahedron: Asymmetry 1991, 2(3), 183-186. Bunnage, M. E.; Davies, S. G.; Goodwin, C. J. J. Chem. Soc., Perkin Trans. 1 1993, 1375-1376. Davies, S. G.; Ichihara, O.; Walter, I. A. S. J. Chem. Soc., Perkin Trans. 1 1994, 1141-1147. Davies, S. G.; Walter, I. A. S. J. Chem. Soc., Perkin Trans. 1 1994, 1129-1139. Bunnage, M. E.; Davies, S. G.; Goodwin, C. J.; Ischihara, O. Tetrahedron 1994, 50, 3975-3986. Davies, S. G.; Bhalay, G. Tetrahedron: Asymmetry 1996, 7(6), 1595. Davies, S. G.; Ichihara, O. Tetrahedron: Asymmetry 1996, 7(7), 1919. Davies, S. G.; Smyth, G. D.; Chippindale, A. M. J. Chem. Soc., Perkin Trans. 1 1999, 3089.
14. Davies, S. G.; Ichihara, O. Tetrahedron: Asymmetry 1991, 2(3), 183-186. Bunnage, M. E.; Davies, S. G.; Goodwin, C. J. J. Chem. Soc., Perkin Trans. 1 1993, 1375-1376. Davies, S. G.; Ichihara, O.; Walter, I. A. S. J. Chem. Soc., Perkin Trans. 1 1994, 1141-1147. Davies, S. G.; Walter, I. A. S. J. Chem. Soc., Perkin Trans. 1 1994, 1129-1139. Bunnage, M. E.; Davies, S. G.; Goodwin, C. J.; Ischihara, O. Tetrahedron 1994, 50, 3975-3986. Davies, S. G.; Bhalay, G. Tetrahedron: Asymmetry 1996, 7(6), 1595. Davies, S. G.; Ichihara, O. Tetrahedron: Asymmetry 1996, 7(7), 1919. Davies, S. G.; Smyth, G. D.; Chippindale, A. M. J. Chem. Soc., Perkin Trans. 1 1999, 3089.
15. Davies, S. G.; Ichihara, O. Tetrahedron: Asymmetry 1991, 2(3), 183-186. Bunnage, M. E.; Davies, S. G.; Goodwin, C. J. J. Chem. Soc., Perkin Trans. 1 1993, 1375-1376. Davies, S. G.; Ichihara, O.; Walter, I. A. S. J. Chem. Soc., Perkin Trans. 1 1994, 1141-1147. Davies, S. G.; Walter, I. A. S. J. Chem. Soc., Perkin Trans. 1 1994, 1129-1139. Bunnage, M. E.; Davies, S. G.; Goodwin, C. J.; Ischihara, O. Tetrahedron 1994, 50, 3975-3986. Davies, S. G.; Bhalay, G. Tetrahedron: Asymmetry 1996, 7(6), 1595. Davies, S. G.; Ichihara, O. Tetrahedron: Asymmetry 1996, 7(7), 1919. Davies, S. G.; Smyth, G. D.; Chippindale, A. M. J. Chem. Soc., Perkin Trans. 1 1999, 3089.
16. Davies, S. G.; Ichihara, O. Tetrahedron: Asymmetry 1991, 2(3), 183-186. Bunnage, M. E.; Davies, S. G.; Goodwin, C. J. J. Chem. Soc., Perkin Trans. 1 1993, 1375-1376. Davies, S. G.; Ichihara, O.; Walter, I. A. S. J. Chem. Soc., Perkin Trans. 1 1994, 1141-1147. Davies, S. G.; Walter, I. A. S. J. Chem. Soc., Perkin Trans. 1 1994, 1129-1139. Bunnage, M. E.; Davies, S. G.; Goodwin, C. J.; Ischihara, O. Tetrahedron 1994, 50, 3975-3986. Davies, S. G.; Bhalay, G. Tetrahedron: Asymmetry 1996, 7(6), 1595. Davies, S. G.; Ichihara, O. Tetrahedron: Asymmetry 1996, 7(7), 1919. Davies, S. G.; Smyth, G. D.; Chippindale, A. M. J. Chem. Soc., Perkin Trans. 1 1999, 3089.
17. In a first approach we applied the Davies chemistry to BOC protected 7-aminohept-2-enoic acid ethyl ester. However, the success of this approach was limited by the difficulty to prepare the BOC-protected aminopentanal which rapidly cyclizes to N-Boc-1,2,3,4-dihydropyridine. Furthermore the Michael addition needs at least two equivalents of the homochiral amine due to proton abstraction at the Boc-amide position. Replacement of the BOC protection with the phthaloyl group did not give the desired addition product. Finally, the N-Boc-N-benzyl protected derivative, which can be easily prepared, revealed to be resistant to the hydrogenolysis at the ω-BOC-position. This last approach was successful, but needed several more steps to obtain the desired molecule (protection of the β-amino moiety, Boc cleavage, debenzylation, protection of the ω-amino group and deprotection of the β-amino position).
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19. An analogous synthesis of trans-2-aminocyclohexane-1-carboxylic acid starting from 7-iodohept-2-enoic acid, tert-butyl ester through Michael addition of a lithiated chiral hydrazine has been recently reported, see: Enders, D.; Wiedemann, J.; Bettray, W. Synlett 1995, 369-371. A synthesis of compound 7 and the enantiomer, through Michael addition to cyclohexenecarboxylic acid tert-butyl ester, followed by a E/Z isomerisation is reported in the literature, see: Davies, S. G.; Ichihara, O.; Walters, I. A. S. Synlett 1993, 461-462. Davies, S. G.; Ichihara, O.; Lenoir, I.; Walters, J. A. S. J. Chem. Soc., Perkin Trans. 1 1994, 1411-1415.
20. An analogous synthesis of trans-2-aminocyclohexane-1-carboxylic acid starting from 7-iodohept-2-enoic acid, tert-butyl ester through Michael addition of a lithiated chiral hydrazine has been recently reported, see: Enders, D.; Wiedemann, J.; Bettray, W. Synlett 1995, 369-371. A synthesis of compound 7 and the enantiomer, through Michael addition to cyclohexenecarboxylic acid tert-butyl ester, followed by a E/Z isomerisation is reported in the literature, see: Davies, S. G.; Ichihara, O.; Walters, I. A. S. Synlett 1993, 461-462. Davies, S. G.; Ichihara, O.; Lenoir, I.; Walters, J. A. S. J. Chem. Soc., Perkin Trans. 1 1994, 1411-1415.
21. An analogous synthesis of trans-2-aminocyclohexane-1-carboxylic acid starting from 7-iodohept-2-enoic acid, tert-butyl ester through Michael addition of a lithiated chiral hydrazine has been recently reported, see: Enders, D.; Wiedemann, J.; Bettray, W. Synlett 1995, 369-371. A synthesis of compound 7 and the enantiomer, through Michael addition to cyclohexenecarboxylic acid tert-butyl ester, followed by a E/Z isomerisation is reported in the literature, see: Davies, S. G.; Ichihara, O.; Walters, I. A. S. Synlett 1993, 461-462. Davies, S. G.; Ichihara, O.; Lenoir, I.; Walters, J. A. S. J. Chem. Soc., Perkin Trans. 1 1994, 1411-1415.
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