- Biocatalysts and methods for the synthesis of armodafinil
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The present invention relates to non-naturally occurring polypeptides useful for preparing armodafinil, polynucleotides encoding the polypeptides, and methods of using the polypeptides. The non-naturally occurring polypeptides of the present invention are effective in carrying out biocatalytic conversion of the (i) 2-(benzhydrylsulfinyl)acetamide to (?)-2-[(R)-(diphenyl-methyl)sulfinyl]acetamide (armodafinil), or (ii) benzhydryl-thioacetic acid to (R)-2-(benzhydrylsulfinyl)acetic acid, which is a pivotal intermediate in the synthesis of armodafinil, in enantiomeric excess.
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Page/Page column 64-65
(2016/05/19)
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- Asymmetric Oxidation Synthesis of Modafinil Acid by Use of a Recyclable Chiral-at-Metal Complex
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The enantioselective oxidation synthesis of chiral modafinil acid and its analogues with high enantiomeric excess has been developed by means of a chiral-at-metal strategy. Treatment of ruthenium complexes cis-[Ru(bpy)2Cl2] or Δ/Λ-[Ru(bpy)2(MeCN)2](PF6)2 (bpy is 2,2′-bipyridine) with the appropriate prochiral thioether ligands afforded thioether complexes rac-1, Δ/Λ-1, rac-2, Δ/Λ-2, rac-3, and Δ/Λ-3. Diastereoselective oxidation of the thioether complexes in situ produced the corresponding sulfoxide complexes rac-1a, Δ/Λ-1a, rac-2a, Δ/Λ-2a, rac-3a, and Δ/Λ-3a. The configuration at the metal center in each case is stable during the coordination and oxidation reactions, and dictates the chirality of the sulfoxide ligand in the oxidation process. The chiral modafinil acids were obtained with ee values greater than 98% upon their removal from the corresponding sulfoxide complexes in the presence of TFA/MeCN. Moreover, the chiral ruthenium precursors Δ/Λ-[Ru(bpy)2(MeCN)2](PF6)2 are recyclable and reusable with complete retention of the configurations. Chiral modafinil acid and its analogues have been synthesized with high ee values by means of asymmetric coordination oxidation of a thioether complex in situ with a chiral-at-metal strategy.
- Li, Zheng-Zheng,Yao, Su-Yang,Wen, A-Hao,Ye, Bao-Hui
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p. 4335 - 4342
(2015/09/15)
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- NOVEL CRYSTALLINE POLYMORPH OF ARMODAFINIL AND AN IMPROVED PROCESS FOR PREPARATION THEREOF
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The present invention relates to a novel crystalline polymorph of armodafinil. In another aspect the invention relates to an improved process for preparation of the novel polymorph of armodafinil.
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Page/Page column 9
(2009/08/16)
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- PROCESSES FOR PREPARING ARMODAFINIL INTERMEDIATE
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The present invention encompasses processes (1) for preparing racemic 2-(benzhydrylsulfinyl)acetic acid by combining the (S)- or the (R)-enantiomer with at least one organic solvent and at least one acid promoter, such as perchloric acid or an acyl halide; (2) for preparing racemic 2-(benzhydrylsulfinyl)acetamide or racemic 2-(benzhydrylsulfinyl)acetic acid by combining the (S)- or the (R)-enantiomer with at least one organic solvent having a boiling point above 60°C, heating to a temperature above 60°C and cooling. The present invention also encompasses the conversion of the racemic intermediates to armodfinil.
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Page/Page column 9 - 10
(2008/12/06)
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- A PROCESS OF SULFOXIDATION OF BIOLOGICALLY ACTIVE COMPOUNDS
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The present invention relates to a new process for the preparation of sulfoxides, preferably stereoselective preparation of substituted or unsubstituted chiral sulfinyl derivatives 2-(2- pyridylmethyl) sulfinyl-l H-benzimidazole by oxidation with oxaziridine in presence of suitable solvent and base.
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Page/Page column 13
(2009/01/24)
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- AN IMPROVED PROCESS FOR THE PREPARATION OF ARMODAFINIL
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The invention encompasses processes for preparing intermediates, such as R-modafinic acid or (R)-C1-2 alkyl ester, of modafinic acid, and the conversion of the intermediates to armodafinil.
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Page/Page column 20
(2008/06/13)
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- Asymmetric synthesis of modafinil and its derivatives by enantioselective oxidation of thioethers: comparison of various methods including synthesis in ionic liquids
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The oxidation of 2-(benzhydrylthio)acetic acid and its derivatives was performed with various catalytic and stoichiometric enantioselective reagents, the best results being obtained with stoichiometric chiral oxaziridine 5. The use of [bmim][PF6] as a solvent with 5 gave slightly higher yields and, in the case of the model compound thioanisole, a reversal of the enantioselectivity.
- Ternois, James,Guillen, Frederic,Plaquevent, Jean-Christophe,Coquerel, Gerard
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p. 2959 - 2964
(2008/09/16)
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- Synthesis and determination of the absolute configuration of the enantiomers of modafinil
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The asymmetric synthesis of both enantiomers of modafinil, a unique CNS stimulant with a reduced abuse liability, is described. This approach effectively prepares modafinil on a multigram scale in several steps from benzhydrol. The described synthetic route has also been used to produce the more water soluble analogue, adrafinil. X-ray crystallographic analysis on (-)-(diphenylmethanesulfinyl)acetic acid has determined the absolute configuration to be R.
- Prisinzano, Thomas,Podobinski, John,Tidgewell, Kevin,Luo, Min,Swenson, Dale
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p. 1053 - 1058
(2007/10/03)
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- Synthesis and determination of the absolute stereochemistry of the enantiomers of adrafinil and modafinil
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Both enantiomers of modafinil, adrafinil, modafinic acid and ethyl modafinate were prepared from the diastereomers formed by reacting racemic β-sulfinyl carboxylic acid with (4R)-phenyl-thiazolidinethione. The absolute stereochemistry of the sulfoxide group was confirmed via X-ray analysis of one of the thiazolidinethione diastereomers.
- Osorio-Lozada, Antonio,Prisinzano, Thomas,Olivo, Horacio F.
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p. 3811 - 3815
(2007/10/03)
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