- Stereoselective amination of racemic sec-alcohols through sequential application of laccases and transaminases
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A one-pot/two-step bienzymatic asymmetric amination of secondary alcohols is disclosed. The approach is based on a sequential strategy involving the use of a laccase/TEMPO catalytic system for the oxidation of alcohols into ketone intermediates, and their following transformation into optically enriched amines by using transaminases. Individual optimizations of the oxidation and biotransamination reactions have been carried out, studying later their applicability in a concurrent process. Therefore, 17 racemic (hetero) aromatic sec-alcohols with different substitutions in the aromatic ring have been converted into enantioenriched amines with good to excellent selectivities (90-99% ee) and conversion values (67-99%). The scalability of the process was also demonstrated when two different amine donors were used in the transamination step, such as isopropylamine and cis-2-buten-1,4-diamine. Satisfyingly, both sacrificial amine donors can shift the equilibrium toward the amine formation, leading to the corresponding isolated enantioenriched amines with good to excellent results.
- Martínez-Montero, Lía,Gotor, Vicente,Gotor-Fernández, Vicente,Lavandera, Iván
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p. 474 - 480
(2017/06/23)
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- MCH antagonists and their use in the treatment of obesity
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Disclosed are compounds represented by structural formula I: or a pharmaceutically acceptable salt, ester or solvate thereof, wherein W is R1—CR3R12NR4C(O)— or R11C(O)NR4—; the dotted line is an optional double bond; X is —CHR8—, —C(O)—, or —C(═NOR9)—; Y is R1is optionally substituted cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocycloalkyl or heterocycloalkyl-alkyl; R2is optionally substituted aryl or heteroaryl; R3is alkyl, aryl or heteroaryl; R4and R12are H or alkyl; R8is H, alkyl or alkoxyalkyl; R9is H, alkyl or arylalkyl; R10is H, alkyl or aryl; R11is or, when R2is R6-heteroaryl or R10is not H, R11can also be R5-phenylalkyl; n is 1-3 and m is 1-5; and R14is 1-3 substituents selected from H, alkyl, halogen, —OH, alkoxy and CF3; and pharmaceutical compositions containing the compounds and methods of using the compounds in the treatment of eating disorders and diabetes.
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