101385-90-4Relevant articles and documents
Natural (-)-vasicine as a novel source of optically pure 1-benzylpyrrolidin-3-ol
Aga, Mushtaq A.,Kumar, Brijesh,Rouf, Abdul,Shah, Bhahwal A.,Andotra, Samar S.,Taneja, Subhash C.
, p. 969 - 977 (2013)
A facile and scalable methodology for the preparation of optically active (3S)-1-benzylpyrrolidin-3-ol (3), an important drug precursor, is reported. Starting from the naturally occurring alkaloid (-)-vasicine (1), a major alkaloid of the plant Adhatoda vasica, 3 was obtained in 84% overall yield (Scheme 3). Copyright
Preparation of optically active N-benzyl-3-hydroxypyrrolidine by enzymatic hydroxylation
Li, Zhi,Feiten, Hans-Juergen,Van Beilen, Jan B.,Duetz, Wouter,Witholt, Bernard
, p. 1323 - 1333 (1999)
Hydroxylation of N-benzylpyrrolidine 2 with Pseudomonas oleovorans GPo1 afforded 62% of (R)-N-benzyl-3-hydroxypyrrolidine 3 in 52% e.e. This reaction was catalyzed by the alkane hydroxylase system in this strain, which was demonstrated by hydroxylation of 2 with Escherichia coli GEc137 (pGEc47), a recombinant strain that carries the genes for the alkane hydroxylase system of P. oleovorans GPo1. In a set of 70 alkane-degrading microorganisms, 12 were found to catalyze the biotransformation of 2 into 3 by screening with a microtiter plate technique. Hydroxylation of 2 with isolates HXN-1100 and HXN-200 gave 67% of (R)-3 in 70% e.e. and 62% of (S)-3 in 53% e.e., respectively.
Inverting the enantioselectivity of P450pyr monooxygenase by directed evolution
Tang, Weng Lin,Li, Zhi,Zhao, Huimin
, p. 5461 - 5463 (2010)
We report the first example of directed evolution of a P450 monooxygenase with inverted enantioselectivity for asymmetric biohydroxylation. The biohydroxylation product of the best mutant 1AF4A has an ee of 83% (R) compared to the wild type's ee of 43% (S). The Royal Society of Chemistry 2010.
Practical synthetic process for enantiopure 1-benzyl-3-hydroxypyrrolidine
Morimoto, Masao,Sakai, Kenichi
, p. 1464 - 1468 (2008)
The synthesis of (S)-1-benzyl-3-hydroxypyrrolidine (S)-5 comprised the asymmetric hydroboration of 1-benzyl-3-pyrroline 4, followed by oxidation and chiral purification via diastereomeric salt formation. The asymmetric borane reagent was generated 'in situ' from NaBH4, BF3-OEt2, and (+)-α-pinene 1 (85% ee) and reacted with 4, prepared from cis-1,4-butenediol 3, to give crude product (S)-5. The following chiral purification via diastereomeric salt formation proceeded to afford (S)-5 with >99% ee. The optimized process was successfully scaled up to an industrial scale to produce a 252 kg batch of (S)-5.
Exploring Derivatives of Quinazoline Alkaloid l-Vasicine as Cap Groups in the Design and Biological Mechanistic Evaluation of Novel Antitumor Histone Deacetylase Inhibitors
Ahmad, Mudassier,Aga, Mushtaq A.,Bhat, Javeed Ahmad,Kumar, Brijesh,Rouf, Abdul,Capalash, Neena,Mintoo, Mubashir Javeed,Kumar, Ashok,Mahajan, Priya,Mondhe, Dilip Manikrao,Nargotra, Amit,Sharma, Parduman Raj,Zargar, Mohmmad Afzal,Vishwakarma, Ram A.,Shah, Bhahwal Ali,Taneja, Subhash Chandra,Hamid, Abid
, p. 3484 - 3497 (2017)
l-Vasicine is a quinazoline alkaloid with an electron dense ring and additional functionalities in its structure. Employing target oriented synthesis (TOS) based on in silico studies, molecules with significant docking scores containing different derivatives of l-vasicine as caps were synthesized. Interestingly, one molecule, i.e., 4a, which contained 3-hyroxypyrrolidine as a cap group and a six carbon long aliphatic chain as a linker was found to inhibit HDACs. 4a showed more specificity toward class I HDAC isoforms. Also 4a was found to be less cytotoxic toward normal cell lines as compared to cancer cell lines. 4a inhibited cancer cell growth and induced cell death by various mechanisms. However, 4a was found to induce cell death independent of ROS generation, and unlike many natural product based HDAC inhibitors, 4a was found to be nontoxic under in vivo conditions. Importantly, we for the first time report the possibility of using a 3-hydroxypyrrolidine cap for the synthesis of HDAC inhibitors with good potency.
Method (S)-3- for -1- synthesizing P-hydroxymethylbenzopyrrolidine (by machine translation)
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Paragraph 0027-0033, (2020/02/14)
After the completion of (S)- 3 - the dropwise addition of the solvent, the reaction liquid,S1, drops are added, into the solvent and then, refluxed, under the (S)- 3, conditions of the temperature under, the conditions 20-65 °C of, the. temperature of the temperature 4 - of the temperature of the reflux ;S2, of (S)4 - the reaction solution, 10-65 °C 10-12h;S3, (S)- 1 -S4, (S)- 1 - 0-65 °C 12-20h;S5, (S)- 3 . (by machine translation)
Stereo-complementary bioreduction of saturated N-heterocyclic ketones
Li, Chao,Liu, Yan,Pei, Xiao-Qiong,Wu, Zhong-Liu
, p. 90 - 97 (2017/04/28)
The asymmetric bioreduction of several saturated N-heterocyclic ketones is demonstrated in a stereo-complementary fashion using the ketoreductases READH and ChKRED20 for the production of (S)- and (R)-alcohols, respectively. The reaction accepts substrates with a five-, six- or seven-membered ring, and exhibits excellent stereoselectivity when using 2-propanol as both the ultimate reducing agent and cosolvent, achieve >99% ee in the majority of cases for both enantiomers.
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.
Synthesis of novel enantiopure ionic liquids from (S)-malic acid
Bonanni, Marco,Manuelli, Massimo,Goti, Andrea,Faggi, Cristina,Cardona, Francesca
, p. 54 - 64 (2014/03/21)
A straightforward and practical synthesis of six novel pyrrolidinium salts based on (S)-malic acid is reported. Two of them were liquid at room temperature, and can be employed as novel chiral ionic liquids for enantioselective applications.ARKAT-USA, Inc.
