287477-53-6Relevant articles and documents
Continuous enzymatic stirred tank reactor cascade with unconventional medium yielding high concentrations of (S)-2-hydroxyphenyl propanone and its derivatives
Glaser, Juliane,Oeggl, Reinhard,Rother, D?rte,von Lieres, Eric
, p. 7886 - 7897 (2021/12/27)
The implementation of biocatalysis in flow chemistry offers synergistic synthesis advantages in line with green chemistry principles. Yet, the conversion of high substrate concentrations is in many cases hindered by insolubility issues or substrate toxicity. Here, the continuous synthesis of (S)-2-hydroxyphenyl propanone (2-HPP) from inexpensive benzaldehyde and acetaldehyde in a methyltert-butyl ether based organic reaction environment, namely micro-aqueous reaction system, has been established. Kinetic parameters of the applied whole cell catalyst were identified to design a continuous process for (S)-2-HPP synthesis. This revealed a necessity to distribute acetaldehyde over a spatial coordinate to remain below a toxic concentration threshold. Hence, three continuous stirred tank reactors (cSTR) were conjugated in a technical cascade with an additional influx of acetaldehyde into each unit. The catalytic behaviour of this reaction setup was described based on mass balances and a kinetic model. Enzyme deactivation was described by a novel staged model and compared to a simple generic model. The optimized continuous setup yielded 190 mM (S)-HPP with an ee > 98% over 8 h. The product was easily recovered from the organic reaction environment by crystallization with an isolated yield of 68% and a purity of >99%. Further, the substrate range of the applied catalystPseudomonas putidabenzoylformate decarboxylase variant L461A was analysed. This revealed numerous halogenated, methoxylated and nitro-derivatives inortho,meta, andparaposition, which can in principle be gained by the established process. As an example, the applied cSTR concept was transferred top-methoxy benzaldehyde with good results even without further optimization.
Synthesis and characterization of in vitro and in vivo profiles of hydroxybupropion analogues: Aids to smoking cessation
Lukas, Ronald J.,Muresan, Ana Z.,Damaj, M. Imad,Blough, Bruce E.,Huang, Xiaodong,Navarro, Hernán A.,Mascarella, S. Wayne,Eaton, J. Brek,Marxer-Miller, Syndia K.,Carroll, F. Ivy
experimental part, p. 4731 - 4748 (2010/10/03)
To create potentially superior aids to smoking cessation and/or antidepressants and to elucidate bupropions possible mechanisms of action(s), 23 analogues based on its active hydroxymetabolite (2S,3S)-4a were synthesized and tested for their abilities to inhibit monoamine uptake and nAChR subtype activities in vitro and acute effects of nicotine in vivo. The 3′,4′-dichlorophenyl [(±)-4n], naphthyl (4r), and 3-chlorophenyl or 3-propyl analogues 4s and 4t, respectively, had higher inhibitory potency and/or absolute selectivity than (2S,3S)-4a for inhibition of DA, NE, or 5HT uptake. The 3′-fluorophenyl, 3′-bromophenyl, and 4-biphenyl analogues 4c, 4d, and 4l, respectively, had higher potency for antagonism of α4β2-nAChR than (2S,3S)-4a. Several analogues also had higher potency than (2S,3S)-4a as antagonists of nicotine-mediated antinociception in the tail-flick assay. The results suggest that compounds acting via some combination of DA, NE, or 5HT inhibition and/or antagonism of α4β2-nAChR can potentially be new pharmacotherapeutics for treatment of nicotine dependence.
