Nanomicelle-enhanced, asymmetric ERED-catalyzed reductions of activated olefins. Applications to 1-pot chemo- and bio-catalysis sequences in water

Abstract

Bio-catalytic reactions involving ene-reductases (EREDs) in tandem with chemo-catalysis in water can be greatly enhanced by the presence ofnanomicelles derived from the surfactant TPGS-750-M. Transformations are provided that illustrate the...

Lipase-catalyzed esterification in water enabled by nanomicelles. Applications to 1-pot multi-step sequences

“…Contributions by the surfactant and additive could be individually evaluated based on the “reservoir effect” first discovered in enzymatic ketone reductions (KREDs). 18 This phenomenon was also observed in the lipase-catalyzed esterification between 3-phenylpropanoic acid 20 and (4-chlorophenyl)methanol 29 leading to ester 9 ( Fig. 3 ).…”

“…Unexpectedly, while the presence of 2 wt% TPGS-750-M ( i.e. , 20 mg mL −1 of water) in the buffered aqueous medium proved beneficial in most cases, increasing the amount to either 4 or 6 wt%, unlike that observed with KRED, 18 led to no further benefit. While these esterifications in water seem unexpected, the key to success may be the presence of the micelles.…”

“…Thus, opportunities for competitive hydrolysis by water are negated due to this “reservoir” effect. 18 …”

“…The benefits to be realized from such a synthetic strategy include not only minimizing workups and thereby, waste creation, but also time invested (“time economy”), 24 and processing (“pot economy”). 25 Importantly, while maintaining global concentrations that typically range between 0.25 and 1 M, 18 the sequence of reactions involving chemo- or bio-catalysis can be varied ( vide infra ).…”

“…30 Thus, and notwithstanding these levels of metal present in the aqueous medium, initial product alcohol 50 was successfully subjected (after adjustment to pH = 2) to lipase-catalyzed esterification. 31 The 1-pot reaction mixture containing ester 51 was subsequently adjusted to pH 7, after which addition of an alcohol dehydrogenase (ADH-101) 18 provided secondary nonracemic alcohol 52 in 59% overall isolated yield (ee >99%).…”