157008-40-7Relevant academic research and scientific papers
Lipase-catalyzed kinetic resolution of trans-2,5-disubstituted pyrrolidine derivatives
Kawanami, Yasuhiro,Moriya, Hitoko,Goto, Yuka,Tsukao, Keiko,Hashimoto, Michihiro
, p. 565 - 570 (1996)
Enantioselective preparation of C2-symmetric (-)-(2S,5S)-N-benzyl-trans-2,5-bis(acetoxymethyl)pyrrolidine was carried out by the lipase-catalyzed hydrolysis of racemic diacetate. Organic co-solvent affected the enantioselectivity and 50% DMSO in the phosphate buffer was found to be the optimal solvent system. A possible active site model was also described.
Influence of 4- or 5-substituents on the pyrrolidine ring of 5-[1-(2-methoxymethylpyrrolidinyl)sulfonyl]isatin derivatives on their inhibitory activities towards caspases-3 and -7 Dedicated to Professor Dr. Ernst-Ulrich Würthwein on the occasion of his 65th birthday
Limpachayaporn, Panupun,Riemann, Burkhard,Kopka, Klaus,Schober, Otmar,Sch?fers, Michael,Haufe, Günter
, p. 562 - 578 (2013/07/11)
A series of new 4- or 5-substituted pyrrolidine derivatives of 5-[1-(2-methoxymethylpyrrolidinyl)sulfonyl]isatin bearing additional n-butyl or 4-fluorobutyl groups at the isatin nitrogen were prepared and their inhibitory activities have been tested against caspases-3 and -7, which are known to participate in the execution of the programmed cell death, called apoptosis. Several analogues fluorinated at the 4-position of the pyrrolidine ring were also synthesized since such inhibitors might be developed as 18F-radiotracers for molecular imaging of activated caspases in vivo by PET. Enantiomerically pure diastereomeric 4-fluoropyrrolidinyl derivatives inhibited the enzymes in the nanomolar scale, i.e.100-1000 times more efficient than the corresponding 4-methoxy analogues. The 4,4-difluorinated compound showed the best result with IC50 = 362 nM and 178 nM for the aforementioned caspases. In contrast, the 4-methoxy and 4-trifluoromethyl analogues exhibited less inhibition potencies for the enzymes in the μM scale, whereas all 4-OPEG4 (PEG4 = tetraethyleneglycol) and 5-methoxymethyl derivatives were inactive.
Symmetry-Assisted Synthesis of C2-Symmetric trans-α,α'-Bis(hydroxymethyl)pyrrolidine and -piperidine Derivatives via Double Sharpless Asymmetric Dihydroxylation of αω-Terminal Dienes
Takahata, Hiroki,Takahashi, Seiki,Kouno, Shin-Ichi,Momose, Takefumi
, p. 2224 - 2231 (2007/10/03)
A new strategy has been developed for the synthesis of C2-symmetric trans-α,α'-bis(hydroxymethyl)pyrrolidine and piperidine derivatives 1-3 starting from symmetric αω-terminal dienes 4-6. The double-asymmetric dihydroxylation (AD) reaction of 4-6 gave C2-symmetric tetrols, which were converted in a four-step sequence to C2-symmetric azacycloalkanes 17,9, and 22, respectively. These azacycloalkanes were transformed into 1-3 in high enantiomeric excess (82% → 98%ee). The double AD reaction proved to cause enantiomeric enhancement, even though the asymmetric induction for the first AD reaction is moderate. In addition, it was observed that the chromatography on silica gel of several C2-symmetric azacycloalkanes (17, 20, and 22) of varying ee's resulted in marked enantiomeric fractionation.
Synthesis of both enantiomers of C2 symmetric trans-2,5- bis(hydroxymethyl)pyrrolidine. Lipase mediated sequential kinetic resolutions
Sibi,Lu
, p. 4915 - 4918 (2007/10/02)
Lipase mediated sequential kinetic resolution has been employed to give both enantiomers of trans-2,5-bis(hydroxymethyl)pyrrolidine in optically pure form. The effect of different parameters on the ee and yields in these resolutions are also reported.
A facile synthesis of optically active C2-symmetric 2,5-disubstituted pyrrolidines and other β,β′-dihydroxyamines
Koh, Kevin,Ben, Robert N.,Durst
, p. 375 - 378 (2007/10/02)
2,5-Dibromoadipic acid has been converted into the di-(R)-pantolactone ester of (S,S)-pyyrolidine-2,5-dicarboxylic acid in two steps. This compound serves as a precursor to C2-symmetric 2,5-disubstituted pyrrolidines. The synthesis of linear C
