Development of Biotransamination Reactions towards the 3,4-Dihydro-2H-1,5-benzoxathiepin-3-amine Enantiomers

Abstract

The stereoselective synthesis of chiral amines is an appealing task nowadays. In this context, biocatalysis plays a crucial role due to the straightforward conversion of prochiral and racemic ketones into enantiopure amines by means of a series of enzyme classes such as amine dehydrogenases, imine reductases, reductive aminases and amine transaminases. In particular, the stereoselective synthesis of 1,5-benzoxathiepin-3-amines have attracted particular attention since they possess remarkable biological profiles; however, their access through biocatalytic methods is unexplored. Amine transaminases are applied herein in the biotransamination of 3,4-dihydro-2H-1,5-benzoxathiepin-3-one, finding suitable enzymes for accessing both target amine enantiomers in high conversion and enantiomeric excess values. Biotransamination experiments have been analysed, trying to optimise the reaction conditions in terms of enzyme loading, temperature and reaction times.

Synthesis of [1,4]Oxathiepino[5,6-b]quinolines via Base-Mediated Intramolecular Hydroalkoxylation

“…It is notable that Vandavasi et al previously studied the synthe-sis of indole/pyrrole-fused 1,4-oxazines. 29 All structures of the newly synthesized compounds were confirmed by 1 H and 13 C NMR spectroscopic and elemental analysis. M.-S. Tonekaboni et al…”

“…Melting points were measured with an Electrothermal 9100 apparatus. NMR spectra were acquired with a Bruker Avance spectrometer at 400 or 300 MHz for 1 H NMR and 100 MHz for 13 C NMR analysis. A Leco CHNS 932 instrument was used for elemental analysis.…”

“…1 H NMR (400 MHz, CDCl 3 ):  = 1.78 (s, 3 H), 4.80 (s, 1 H), 5.41 (s, 2 H), 7.52-7.57 (m, 1 H), 7.72-7.82 (m, 2 H), 7.97 (t, J = 12 Hz, 1 H). 13 C NMR (100 MHz, CDCl 3 ):  = 23.1, 70.2, 85.9, 126.6, 126.7, 127.6, 128.6, 130.6, 132.9, 136.6, 147.4, 154.9.…”

“…11,12 Oxathiepines rank among the less studied heterocycles, although groups have reported several compounds possessing (R,S)-benzo-fused, seven-membered rings with oxygen and sulfur atoms in a 1,5-relationship with interesting antiproliferative activities against the MCF-7 cancer cell line (Figure 1). 13,14…”

Biocatalysis and Pharmaceuticals: A Smart Tool for Sustainable Development

“…Two contributions in this Special Issue focus on this area. Campos, Gotor-Fernández, and coworkers apply a broad panel of commercially available amine transaminases (ATAs) for the biotransanimation of 3,4-dihydro-2H-1,5-benzoxathiepin-3-one (the chemical synthesis of which is reported via some previously undescribed intermediates) to furnish the correspondent enantiopure amines [91]. The optimization of the reaction conditions (enzyme loading, temperature, and reaction times) using ATA03 from Neosartorya fischeri and ATA07 from Mycobacterium vanbaalenii (leading to the (S)-amine), as well as TA-P1-G05 for the (R)-counterpart, allowed a milligram-scale synthesis of the pure amines, which are useful as building blocks for the preparation of antiproliferative drugs.…”