Synthesis of Pharmaceutically Relevant 2-Aminotetralin and 3-Aminochroman Derivatives via Enzymatic Reductive Amination
2-Aminotetralin and 3-aminochroman derivatives are key structural motifs present in a wide range of pharmaceutically important molecules. Herein, we report an effective biocatalytic approach towards these molecules through the enantioselective reductive coupling of 2-tetralones and 3-chromanones with a diverse range of primary amine partners. Metagenomic imine reductases (IREDs) were employed as the biocatalysts, obtaining high yields and enantiocomplementary selectivity for >15 examples at preparative scale, including the precursors to Ebalzotan, Robalzotan, Alnespirone and 5-OH-DPAT. We also present a convergent chemo-enzymatic total synthesis of the Parkinson's disease therapy Rotigotine in 63 % overall yield and 92 % ee.
Citoler, Joan,Harawa, Vanessa,Marshall, James R.,Bevinakatti, Han,Finnigan, James D.,Charnock, Simon J.,Turner, Nicholas J.
supporting information
p. 24456 - 24460
(2021/10/19)
S-5-SUBSTITUENT-N-2'-(THIOPHENE-2-YL)ETHYL-TETRALIN-2-AMINE OR CHIRAL ACID SALTS THEREOF AND USE FOR PREPARING ROTIGOTINE
The chiral compound S-5-substituted-N-2′-(thienyl-2-yl-)ethyl-tetralin-2-amine or its chiral acid salts and preparation method thereof are disclosed, and the method for preparing Rotigotine by using the chiral compound is also disclosed. Racemic 5-substituted-N-2′-(thien-2-yl-)ethyl-tetralin-2-amine (compound 1) is resolved by using a conventional chiral acid to obtain an optically pure chiral acid salt of S-5-substituted-N-2′-(thien-2-yl-)ethyl-tetralin-2-amine, which is then dissociated to obtain S-5-substituted-N-2′-(thien-2-yl-)ethyl-tetralin-2-amine (compound 2). The compound 2 or chiral acid salt thereof is alkylated and deprotected to produce rotigotine (compound 5).
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Paragraph 0036; 0037
(2013/03/26)
S-5-SUBSTITUENT-N-2'-(THIOPHENE-2-YL)ETHYL-TETRALIN-2-AMINE OR CHIRAL ACID SALTS THEREOF AND USE FOR PREPARING ROTIGOTINE
The chiral compound S-5-substituted-N-2-(thienyl-2-yl-)ethyl-tetralin-2-amine or its chiral acid salts and preparation method thereof are disclosed, and the method for preparing Rotigotine by using the chiral compound is also disclosed. Racemic 5-substituted-N-2'-(thien-2-yl-)ethyl-tetralin-2-amine (compound 1) is resolved by using a conventional chiral acid to obtain an optically pure chiral acid salt of S-5-substituted-N,2'-(thien-2-yl-)ethyl-tetralin-2-amine, which is then dissociated to obtain S-5-substituted-N-2'-(thien-2-yl-)ethyl-tetralin-2-amine (compound 2). The compound 2 or chiral acid salt thereof is alkylated and deprotected to produce rotigotine (compound 5).
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Page/Page column 6
(2012/07/28)
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