199391-75-8Relevant articles and documents
Tasimelteon intermediate and preparation method thereof
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, (2017/04/27)
The invention provides a tasimelteon intermediate and a preparation method thereof. The preparation method comprises the following steps: with a compound a as a raw material, reacting the compound a with benzyl bromide so as to obtain a compound I; then subjecting the compound I to a reaction under the action of a combined catalyst consisting of potassium osmate dihydrate, potassium carbonate, potassium ferricyanide, benzyltriethylammonium chloride and methane sulfonamide or a combined catalyst consisting of osmium tetroxide, potassium carbonate, potassium ferricyanide, benzyltriethylammonium chloride and methane sulfonamide so as to obtain a compound II; subjecting the compound II to an oxidation reaction under the action of sodium periodate or lead tetraacetate so as to obtain an intermediate compound III and carrying out a reduction reaction so as to obtain a compound IV; and subjecting the compound IV to a reduction reaction to remove a benzyl protective group so as to obtain a compound V, then reacting the compound V with p-toluene sulfonyl chloride, carrying out hydroxyl protection and then carrying out cyclization under the action of potassium carbonate so as to obtain the tasimelteon intermediate compound VI. The invention provides a novel process for preparation of the tasimelteon intermediate; and the prepared tasimelteon intermediate has good purity and high quality and is applicable to industrial production.
Gram-Scale Synthesis of Chiral Cyclopropane-Containing Drugs and Drug Precursors with Engineered Myoglobin Catalysts Featuring Complementary Stereoselectivity
Bajaj, Priyanka,Sreenilayam, Gopeekrishnan,Tyagi, Vikas,Fasan, Rudi
supporting information, p. 16110 - 16114 (2016/12/26)
Engineered hemoproteins have recently emerged as promising systems for promoting asymmetric cyclopropanations, but variants featuring predictable, complementary stereoselectivity in these reactions have remained elusive. In this study, a rationally driven strategy was implemented and applied to engineer myoglobin variants capable of providing access to 1-carboxy-2-aryl-cyclopropanes with high trans-(1R,2R) selectivity and catalytic activity. The stereoselectivity of these cyclopropanation biocatalysts complements that of trans-(1S,2S)-selective variants developed here and previously. In combination with whole-cell biotransformations, these stereocomplementary biocatalysts enabled the multigram synthesis of the chiral cyclopropane core of four drugs (Tranylcypromine, Tasimelteon, Ticagrelor, and a TRPV1 inhibitor) in high yield and with excellent diastereo- and enantioselectivity (98–99.9% de; 96–99.9% ee). These biocatalytic strategies outperform currently available methods to produce these drugs.
ACYL GUANIDINE SODIUM/PROTON EXCHANGE INHIBITORS AND METHOD
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Page/Page column 32, (2010/02/10)
Acyl guanidines are provided which are sodium/proton exchange (NHE) inhibitors which have the structure wherein n is 1 to 5; X is N or C-R5 wherein R5 is H, halo, alkenyl, alkynyl, alkoxy, alkyl, aryl or heteroaryl; and R1, R2, R3 and R4 are as defined herein, and where X is N, R1 is preferably aryl or heteroaryl, and are useful as antianginal and cardioprotective agents. In addition, a method is provided for preventing or treating angina pectoris, cardiac dysfunction, myocardial necrosis, and arrhythmia employing the above acyl guanidines.