- Preparation method of antihypertensive medicine key intermediate of trans-4-cyclohexyl-L-proline
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The invention discloses a preparation method of trans-4-cyclohexyl-L-proline. The method comprises the following steps of (1) under the effect of an acid-binding agent, 4S-hydroxy-N-Boc-L-proline ester 6 and sulfonyl chloride are subjected to condensation to generate sulphonate 5, wherein R is C1-4 alkyl; (2) under the effects of a copper catalyst, lithium salt and organic alkali, the sulphonate 5and cyclohexylmagnesium bromide take nucleophilic substitution to generate a compound 4; (3) the compound 4 is hydrolyzed by lithium hydroxide to obtain (4S)-N-Boc-4-cyclohexyl-L-proline (a compound3); (4) the compound 3 is subjected to Boc removal under the condition of hydrochloric acid or trifluoroacetic acid/methylene dichloride; a target product 2 is prepared. The preparation method has thebeneficial effects that the target product structure and chirality are introduced through sulphonate and Grignard reagent nucleophilic substitution; the defects of the existing noble metal reductionmethod are overcome; the operation of the method is simple; the conditions are mild; the yield is good; the chemical purity and the optical purity are very high; the preparation method is suitable forindustrial production.
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- Proline compounds as Granzyme B inhibitors
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Proline compounds as Granzyme B inhibitors, compositions that include the compounds, and methods for using the compounds. Methods for treating cutaneous scleroderma, epidermolysis bullosa, radiation dermatitis, alopecia areata, and discoid lupus erythematosus are provided.
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Page/Page column 54; 55
(2016/10/27)
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- Design and synthesis of long-acting inhibitors of dipeptidyl peptidase IV
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A series of (4-substituted prolyl)prolinenitriles were synthesized and evaluated as inhibitors of dipeptidylpeptidase IV (DPP-IV). Among those tested, the 4β-[4-(hydroxyphenyl)prolyl]prolinenitriles showed a potent inhibitory activity with a long duration
- Kondo, Takashi,Sugimoto, Isamu,Nekado, Takahiro,Ochi, Kenya,Ohtani, Tazumi,Tajima, Yohei,Yamamoto, Susumu,Kawabata, Kazuhito,Nakai, Hisao,Toda, Masaaki
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p. 2715 - 2735
(2008/02/08)
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- Novel peptides as NS3-serine protease inhibitors of hepatitis C virus
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The present invention discloses novel compounds which have HCV protease inhibitory activity as well as methods for preparing such compounds. In another embodiment, the invention discloses pharmaceutical compositions comprising such compounds as well as methods of using them to treat disorders associated with the HCV protease.
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