Decarboxylation of α-Amino Acids Containing Two and Three Stereogenic Centers: A Simple One-Step Procedure to Prepare two Optically Active β-Amino Alcohols and a Bicyclic Pyrrolidine Derivative

Organocatalytic Decarboxylation of Amino Acids as a Route to Bio‐based Amines and Amides

“…The decarboxylation of phenylalanine ( 1 a ) to 2‐phenethylamine ( 2 a ) was studied as a model reaction to assess the intrinsic catalytic activity of different carbonyl compounds under relatively mild conditions (Table ; additional examples in the Supporting Information (Table S1)). To that end, a catalyst loading of 5 mol% was applied, which is low in comparison with previous studies . The thermal decarboxylation of 1 a at 130 °C – in the absence of any additional carbonyl compound – occurred only to a limited extent (entry 1).…”

“…To that end, a catalyst loading of 5 mol% was applied, which is low in comparison with previous studies. [36][37][38][39][40][41][42][43][44][45][46][47][48][49][50] The thermal decarboxylation of 1 a at 130°C -in the absence of any additional carbonyl compound -occurred only to a limited extent (entry 1). First, structural analogues of PLP and the pyruvoyl cofactor present in amino acid decarboxylases were selected as potential organocatalysts, but pyridine-4-carbaldehyde, 4-acetylpyridine and methyl pyruvate showed no activity (entries 2-4).…”

“…[35] In an attempt to mimic the enzymatic approach, both aliphatic and aromatic carbonyl compounds have been proposed as suitable mediators for amino acid decarboxylation. Although these compounds have often been evaluated as stoichiometric reagents, [36][37][38][39][40][41][42][43][44][45][46][47][48][49][50] they are not consumed according to the mechanism (Scheme 1). However, their ability to act as a catalyst has only rarely been exploited before.…”

“…Promising results were obtained for α,β-unsaturated ketones like 2-cyclohexen-1one in certain case studies, but reactions were still applied with rather high catalyst loadings and at high temperature. [41][42][43][44][45][46][47][48][49][50] Therefore, this study aims to identify a performant organocatalyst for amino acid decarboxylation, which is active at low loadings (� 5 mol%) and under relatively mild conditions (� 150°C).…”

Engineering of recombinant E. coli cells co‐expressing P450pyrTM monooxygenase and glucose dehydrogenase for highly regio‐ and stereoselective hydroxylation of alicycles with cofactor recycling

“…HXN‐200, a class I P450 requiring ferredoxin (Fdx) and ferredoxin reductase (FdR) for electron transfer, for the hydroxylation at non‐activated carbon atom with unique substrate specificity, broad substrate range, and good to excellent regio‐ and stereoselectivity (Chang et al, 2000, 2002a, b; Li et al, 1999, 2001). It represents the best hydroxylation system known thus far for the hydroxylation of a series of alicycles such as N ‐substituted pyrrolidines (Li et al, 1999, 2001), pyrrolidinones (Chang et al, 2000), piperidines (Chang et al, 2002b), piperidinones (Chang et al, 2002a), and azetidines (Chang et al, 2002b) to prepare the corresponding alcohols as useful and valuable pharmaceutical intermediates (Fromtling and Castaner, 1995; Nagahara et al, 1994; Wallbaum et al, 1994; Weber and Gmeiner, 1998). To improve the enantioselectivity in the hydroxylation of N ‐benzyl pyrrolidine, we performed the directed evolution of P450pyr hydroxylase.…”