124445-27-8Relevant articles and documents
Preparation of enantiomerically pure N-heterocyclic amino alcohols by enzymatic kinetic resolution
Tofani, Giorgio,Petri, Antonella,Piccolo, Oreste
, p. 638 - 643 (2015/08/03)
Abstract The synthesis of both enantiomers of N-benzyl-3-hydroxypyrrolidine and N-benzyl-3-hydroxypiperidine via enzymatic kinetic resolution of the corresponding racemic esters is described. Various commercially available hydrolases were studied as biocatalysts in native and immobilized form. The best results were obtained with lipases PS, AK, CAL-B and with protease Alcalase, which were active and selective for the kinetic resolutions of racemic esters (E > 100). Under optimized reaction conditions, highly enantiomerically enriched (up to 99.5% ee) resolution products were obtained. Lipase and protease showed opposite enantiopreference on the esters, allowing the preparation of both enantiomers of the target compounds. Semi-continuous reactions in column reactors with immobilized biocatalysts were also performed with high enantioselectivities. Inversion of the configuration at C(3) of N-benzyl-3-hydroxypyrrolidine was quantitatively effected in a short number of steps.
3-Hydroxypyrrolidine and (3,4)-dihydroxypyrrolidine derivatives: Inhibition of rat intestinal α-glucosidase
Carreiro, Elisabete P.,Louro, Patrícia,Adriano, Gizé,Guedes, Romina A.,Vannuchi, Nicholas,Costa, Ana R.,Antunes, Célia M.M.,Guedes, Rita C.,Burke
, p. 81 - 88 (2014/06/09)
Thirteen pyrrolidine-based iminosugar derivatives have been synthesized and evaluated for inhibition of α-glucosidase from rat intestine. The compounds studied were the non-hydroxy, mono-hydroxy and dihydroxypyrrolidines. All the compounds were N-benzylated apart from one. Four of the compounds had a carbonyl group in the 2,5-position of the pyrrolidine ring. The most promising iminosugar was the trans-3,4-dihydroxypyrrolidine 5 giving an IC50 of 2.97 ± 0.046 and a KI of 1.18 mM. Kinetic studies showed that the inhibition was of the mixed type, but predominantly competitive for all the compounds tested. Toxicological assay results showed that the compounds have low toxicity. Docking studies showed that all the compounds occupy the same region as the DNJ inhibitor on the enzyme binding site with the most active compounds establishing similar interactions with key residues. Our studies suggest that a rotation of ～90° of some compounds inside the binding pocket is responsible for the complete loss of inhibitory activity. Despite the fact that activity was found only in the mM range, these compounds have served as simple molecular tools for probing the structural features of the enzyme, so that inhibition can be improved in further studies.
PYRIDONE DERIVATIVE
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Page/Page column 102, (2010/11/25)
The invention provides pyridone derivatives represented by a general formula (I) [in the formula, R 1 and R 2 may be same or different and stands for H, etc., or R 1 and R 2 may form an aliphatic nitrogen-containing heterocyclic group together with the N to which they bind; X 1 -X 3 may be same or different and stand for methine or N, provided not all of them simultaneously stand for nitrogen; X 4 -X 7 may be same or different and stand for methine or N, provided that three or more of them do not simultaneously stand for N; Y 1 and Y 3 may be same or different and stand for single bond, -0-, -NR-, -S-, etc ; Y 2 stands for lower lkylene, etc.; R stands for H, etc., L stands for methylene; Z 1 and Z 2 may be same or different and stand for single bond or lower alkylene; or R 1 , L and Z 2 may form an aliphatic nitrogen-containing heterocyclic group with the N to which R 1 binds; and Ar stands for aromatic carbocyclic group, etc.].
Lipase-catalyzed practical synthesis of (R)-1-benzyl-3-hydroxy-2,5-pyrrolidinedione and its related compounds
Tomori, Hiroshi,Shibutani, Kuniko,Ogura, Katsuyuki
, p. 207 - 215 (2007/10/03)
A practical method for preparing (R)-1-benzyl-3-hydroxy-2,5-pyrrolidinedione (1) was investigated by the use of the enzymatic hydrolysis of its acetate (2a). Among several hydrolases examined here, lipase PS from Pseudomonas cepacia gave the best result: In a mixed solvent (1:1 v/v) of dioxane and a phosphate buffer (pH 7), the hydrolysis took place smoothly with a high enantioselectivity (E > 3000). Several 3-alkanoyl derivatives of 1 were subjected to the lipase PS-catalyzed hydrolysis. The chain length of the alkanoyl does not noticeably influence the reaction rate or the enantioselectivity. In contrast, the hydrolysis of the 1-benzoyl derivative proceeded slowly with a low enantioselectivity (E = 19). The syntheses of optically active 3-hydroxypyrrolidines and 3-hydroxypiperidines were also achieved under the reaction conditions similar to the lipase PS-catalyzed hydrolysis of 2a.
