394734-77-1Relevant articles and documents
Preparation method of antihypertensive medicine key intermediate of trans-4-cyclohexyl-L-proline
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, (2018/11/22)
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.
Design and synthesis of long-acting inhibitors of dipeptidyl peptidase IV
Kondo, Takashi,Sugimoto, Isamu,Nekado, Takahiro,Ochi, Kenya,Ohtani, Tazumi,Tajima, Yohei,Yamamoto, Susumu,Kawabata, Kazuhito,Nakai, Hisao,Toda, Masaaki
, p. 2715 - 2735 (2008/02/08)
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
