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Chiral amine compound and its synthesis and use

A synthesis method and technology of chiral amines, applied in the field of chiral amine compounds, can solve problems such as narrow substrate range

Inactive Publication Date: 2002-01-23
SHANGHAI INST OF ORGANIC CHEM CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] Although this method has obtained better results, it is only limited to the reaction of phenylalaninaldehyde 3 and nitromethane, and the range of substrates is narrow.
Moreover, the chiral inducers used are also limited to quaternary ammonium salts of cinchonine

Method used

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  • Chiral amine compound and its synthesis and use

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0025] Reaction 4

[0026] Dissolve 50 mg of N,N-dibenzyl-(S)-phenylalaninaldehyde 5 (0.15 mmol) in 1.5 mL of toluene, then add 6 mg of 1,3-N,N-di-(R)-α-naphthalene Etamine 8, after cooling to -20°C, 0.2 mL of nitromethane was added dropwise, reacted for 12 hours, and 55 mg of the post-treated product was obtained, with a total yield of 92%. d.e. >99%. 1 HNMR (300MHz, CDCL 3 )δ compound 6: 7.32 (m, 15H), 4.85 (dd, 1H, J 1 =12.0Hz,J 2 =3.0Hz), 4.53(m, 1H), 4.06(dd, 1H, J 1 =13.5Hz,J 2 =9.9Hz), 3.84(d, 2H, J=13.5Hz), 3.57(d, 2H, J=13.5Hz), 3.20(dd, 1H, J 1 =6.0Hz,J 2 =3.3Hz), 3.08(m, 2H), 2.53(s, 1H).ESIMS: (M+H) + 391.3. Compound 7: 7.32 (m, 15H), 4.19-4.33 (m, 2H), 4.13 (d, 2H, J=13.2Hz), 3.95 (s, 1H), 3.83 (d, 1H, J=21.3Hz), 3.49(d, 2H, J=13.2Hz), 3.24(d, 1H, J=11.4Hz), 2.86(m, 2H); ESIMS: (M+H) + 391.3.

Embodiment 2

[0028] Dissolve 50mg of N,N-dibenzyl-(S)-phenylalaninaldehyde 5 (0.15mmol) in 1.5mL of toluene, then add 6mg of guanidine 9, cool to -20°C and add 0.2mL of nitromethane dropwise, After 12 hours of reaction, 55 mg of product was obtained after post-treatment, with a total yield of 89%. d.e. = 93.3%. The structural data are the same as in Example 1.

Embodiment 3

[0030] Dissolve 50mg of N,N-dibenzyl-(S)-phenylalaninaldehyde 5 (0.15mmol) in 1.5mL of toluene, then add 6mg of guanidine 10, cool to -20C, and drop 0.2mL of nitromethane into the reaction After 12 hours, 55 mg of the product was obtained after post-treatment, with a yield of 97%. d.e. = 93.3%. The structural data are the same as in Example 1. Example 4

[0031] Dissolve 50mg of N,N-dibenzyl-(S)-phenylalaninaldehyde 5 (0.15mmol) in 1.5mL of toluene, then add 6mg of guanidine 11, cool to -20°C and add 0.2mL of nitromethane dropwise, After 18 hours of reaction, 55 mg of product was obtained after post-treatment, with a total yield of 91%. d.e. = 57.4%. The structural data are the same as in Example 1.

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Abstract

The present invention relates to a chiral amine compound. It is prepared through asymmetrical Henry reaction of amino aldehyde, obtained through the conversion of amino acid and amino alcohol, as acceptor with nitro alkane with molecular formula of R6NO2 in the presence of chiral carbamidine as catalyst. The compound may be used to synthesize a HIV proteinase inhibitor with wide application.

Description

technical field [0001] The invention relates to a chiral amine compound, which is prepared by the asymmetric Henry reaction of aminoaldehyde and nitroalkane under the catalysis of chiral guanidine. The compound can be used for synthesizing HIV protease inhibitor with wide application. Background technique [0002] The nucleophilic addition reaction of aldehydes to nitroalkanes (called Henry reaction, also known as Nitroaldol reaction) is one of the oldest and important methods for building C-C bonds. However, the Henry reaction using guanidine as a catalyst was first reported in the early 1990s. It uses tetramethylguanidine (TMG) as a catalyst to catalyze the reaction of L-glucose and nitromethane (A.C.Forsyth, R.M.Paton, I.Watt., Tetrahedron Letter, 1989, 30, 993.). In 1994, R. Chinchilla etc. first reported the Henry reaction of alkyl aldehydes and nitromethane with chiral guanidine as catalysis, and obtained the highest e.e value of 54% (R. Chinchlla, C. Najera, Tetrahed...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C215/06C07C215/08C07C215/28C07C217/26C07C217/48C07C229/20C07C229/34C07C233/16C07C323/24
Inventor 马大为韩福社
Owner SHANGHAI INST OF ORGANIC CHEM CHINESE ACAD OF SCI