- Synthesis method of chiral N-Boc-3-amino-4-aryl-butyric acid
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The invention relates to a synthesis method of chiral N-Boc-3-amino-4-aryl-butyric acid. The method is as below: 1, conducting a cross metathesis reaction, an asymmetric conjugate addition reaction and an oxidation reaction on starting materials including an allyl aromatic compound and crotonaldehyde by a continuous reaction one-pot method to synthesize an N-Boc-3-aryl methyl-5-oxo isoxazole intermediate; or conducting an asymmetric conjugate addition reaction and an oxidation reaction on a starting material (E)-4-aryl-2-crotonaldehyde by a continuous reaction one-pot method to synthesize an N-Boc-3-aryl methyl-5-oxo isoxazole intermediate; and 2, subjecting (3R)-N-Boc-3-aryl methyl-5-oxo isoxazole intermediate by high-pressure hydrogenation to directly prepare the chiral N-Boc-3-amino-4-aryl-butyric acid. The synthesis method provided by the invention has the advantages of simple operation, mild reaction conditions, target product yield reaching 60-69%, and ee value of the target product reaching as high as 96%. The synthetic route has industrialization prospect.
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Paragraph 0032; 0033; 0034; 0035; 0037; 0044
(2017/08/28)
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- Discovery of potent and selective β-homophenylalanine based dipeptidyl peptidase IV inhibitors
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Modification of in-house screening lead β-aminoacyl proline 8 gave an equipotent thiazolidide 9. Extensive SAR studies on the phenyl ring of 9 led to the discovery of a novel series of potent and selective DP-IV inhibitors. Introduction of a fluorine at the 2-position proved to be crucial for the potency of this series. The 2,5-difluoro (22q) and 2,4,5-trifluoro (22t) analogues were potent inhibitors of DP-IV (IC50 = 270, 119 nM, respectively).
- Xu, Jinyou,Ok, Hyun O.,Gonzalez, Edward J.,Colwell Jr., Lawrence F.,Habulihaz, Bahanu,He, Huaibing,Leiting, Barbara,Lyons, Kathryn A.,Marsilio, Frank,Patel, Reshma A.,Wu, Joseph K.,Thornberry, Nancy A.,Weber, Ann E.,Parmee, Emma R.
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p. 4759 - 4762
(2007/10/03)
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