- First total synthesis of (±)-3-hydroxy-11-norcytisine: Structure confirmation and biological characterization
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(Chemical Equation Presented) The first total synthesis of the natural product 3-hydroxy-11-norcytisine (1), structurally related to cytisine (2), a benchmark ligand at neuronal nicotlnic acetylcholine receptors (NNRs), has been achieved. The synthesis permits the unambiguous confirmation of the structure originally proposed for 1 and has enabled initial biological characterization of 1 and its related compounds against NNRs.
- Yohannes, Daniel,Hansen, Camilla P.,Akireddy, Srinivasa Rao,Hauser, Terry A.,Kiser, Melanie N.,Gurnon, Nicholas J.,Day, Cynthia S.,Bhatti, Balwinder,Caldwell, William S.
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- Method for synthesizing N-Boc-3-pyrrolidine formaldehyde
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The invention discloses a method for synthesizing N-Boc-3-pyrrolidine formaldehyde. The method comprises that dimethyl itaconate as a raw material undergoes an intramolecular cyclization reaction to produce methyl 5-oxo-3-pyrrolidine carboxylate, then the methyl 5-oxo-3-pyrrolidine carboxylate undergoes a reduction reaction to produce pyrrolidine-3-methanol, then the pyrrolidine-3-methanol is subjected to Boc protection so that N-Boc-pyrrolidine-3-methanol is obtained, and finally, the N-Boc-pyrrolidine-3-methanol is oxidized to form a final product compound. The method is simple and convenient, has a low cost, content greater than 99%, produces small environmental pollution and is suitable for industrial production.
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Paragraph 0032; 0033; 0038; 0043
(2017/06/02)
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- Synthesis of Boc-protected 4,5-methano-β-proline
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An efficient method for the preparation of Boc-protected 4,5-methano-β-proline - a novel bicyclic cyclopropane-containing β-amino acid - was developed, starting from readily available itaconic acid. A modified Simmons-Smith reaction was used for the construction of the cyclopropane ring. The method allowed for the synthesis of both cis and trans isomers of the title compound in 49% total yield and can be employed for gram-scale preparations. An approach to the preparation of methyl 5-oxopyrrolidine-3-carboxylate, which is one of the key intermediates in the synthetic scheme, on a multigram scale was also developed.
- Tymtsunik, Andriy V.,Ivon, Yevhen M.,Komarov, Igor V.,Grygorenko, Oleksandr O.
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p. 3312 - 3315
(2014/06/09)
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- A chemoenzymatic approach to the synthesis of enantiomerically pure aza analogues of paraconic acid methyl ester and both enantiomers of methyl β-proline
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Enantiopure methyl esters of 1-alkyl-5-oxo-3-pyrrolidinecarboxylic acids were obtained by enzymatic resolution of the corresponding chiral racemic mixtures. A particularly favourable interaction, also supported by molecular mechanics calculations, was observed between the 1-benzyl derivative and α-chymotrypsin, for which the enantiomeric ratio, E, exceeded 200. The absolute configurations of the lactams were determined by means of CD spectroscopy. From the resulting enantiomerically pure (99% e.e.) (S)-(+)-1-benzyl-3-pyrrolidinecarboxylic acid and methyl (R)-(-)-1-benzyl-3-pyrrolidinecarboxylate, the methyl esters of (+) and (-)-β-proline were synthesised in 99% e.e. and 18 and 22% overall yield, respectively.
- Felluga, Fulvia,Pitacco, Giuliana,Prodan, Massimo,Pricl, Sabrina,Visintin, Marco,Valentin, Ennio
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p. 3241 - 3249
(2007/10/03)
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- THERAPEUTIC AGENT FOR DIABETES
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A therapeutic agent for diabetes, which comprises a compound of the formula [I] wherein Xis a group of the formula wherein R4and R5are the same or different and each is a hydrogen atom, an optionally substituted alkyl having 1 to 5 carbon atoms and the like, and R6is a hydrogen atom or an amino-protecting group; R1is an optionally substituted alkyl having 1 to 5 carbon atoms, an optionally substituted alkenyl having 2 to 6 carbon atoms and the like, R2is a hydrogen atom, an optionally substituted alkyl having 1 to 5 carbon atoms and the like, R2' is a hydrogen atom, and R3is an optionally substituted alkyl having 1 to 5 carbon atoms and the like, a prodrug thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof and a solvate thereof. The compound of the present invention shows superior blood sugar decreasing action on the state of hyperglycemia, but does not affect the blood sugar when it is in the normal range or in the hypoglycemic state, which means that it is free of serious side effects such as hypoglycemia. Therefore, the compound of the present invention is useful as a therapeutic drug for diabetes and also useful as a preventive of the chronic complications of diabetes.
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- Synthetic Versatility of N(Silylmethyl)imines: Water-Induced Generation of N-Protonated Azomethine Ylides of Nonstabilized Type and Fluoride-Induced Generation of 2-Azallyl Anions
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N-(Silylmethyl)imines generate N-protonated azomethine ylides of nonstabilized type when treated with water in HMPA, which undergo stereospecific and regioselective cycloadditions with electron-poor olefins affording N-unsubstituted pyrrolidines.On the other hand, fluoride-induced desilylation of the imines leads to 2-azallyl anions which are found to be synthetic equivalents of aminomethyl anion in the Michael additions with electron-poor olefins and nucleophilic additions with carbonyl compounds.
- Tsuge, Otohiko,Kanemasa, Shuji,Hatada, Akira,Matsuda, Koyo
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p. 2537 - 2546
(2007/10/02)
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