Two complementary strategies for the synthesis of febrifugine are detailed based on previously developed chemoenzymatic approaches to the 3-hydroxypiperidine skeleton. The introduction of the quinazolone-containing side chain in both strategies was based on an N-acyliminium ion-mediated coupling reaction.

Chemoenzymatic reaction cascades can provide access to chiral compounds from low-cost starting materials in one pot. Here we describe one-pot asymmetric routes to tetrahydroisoquinoline alkaloids (THIAs) using the Pictet-Spenglerase norcoclaurine synthase (NCS) followed by a cyclisation, to give alkaloids with two new heterocyclic rings. These reactions operated with a high atom economy to gene...

A chemoenzymatic approach for the asymmetric total synthesis of the title compounds is described that employs an enantioselective oxidative C-C bond formation catalyzed by berberine bridge enzyme (BBE) in the asymmetric key step. This unique reaction yielded enantiomerically pure (R)-benzylisoquinoline derivatives and (S)-berbines such as the natural product (S)-scoulerine, a sedative and muscl...

The chemical step in the chemoenzymatic synthesis of bioengineered heparin has been examined and optimized statistically using a response surface methodology. A four factor, two level full factorial design experiment and a three factor Box-Behnken design were carried out. The goal was to establish a method to prepare N-sulfo, N-acetyl heparosan of the desired N-acetyl content, number average mo...

A two-step strategy for disaccharide modulation using vancomycin as a model is reported. The strategy relies upon a glycosyltransferase-catalyzed 'reverse' reaction to enable the facile attachment of an alkoxyamine-bearing sugar to the vancomycin core. Neoglycosylation of the corresponding aglycon led to a novel set of vancomycin 1,6-disaccharide variants. While the in vitro antibacterial prope...

A novel chemoenzymatic one-pot multicomponent synthesis of thiazole derivatives was developed. A series of thiazole derivatives were synthesized with high yields up to 94% under mild enzyme-catalyzed conditions. The blank and control experiments reveal that trypsin from porcine pancreas (PPT) displayed great catalytic activity to promote this reaction and showed a wide tolerance range towards d...

The trans-o-hydroxybenzylidene pyruvate aldolase-catalysed reactions between fluoropyruvate and many (hetero)aromatic aldehydes yield aldol adducts without subsequent dehydration. Treatment of the reaction products with hydrogen peroxide yields the corresponding syn-configured α-fluoro β-hydroxy carboxylic acids which have >98 % ee. The overall chemoenzymatic approach, in which fluoropyruvate s...

Pterin-containing natural products have diverse functions in life, but an efficient and easy scheme for their in vitro synthesis is not available. Here we report a chemoenzymatic 14-step, one-pot synthesis that can be used to generate 13C- and 15N-labeled dihydrofolates (H2F) from glucose, guanine, and p-aminobenzoyl-l-glutamic acid. This synthesis stands out from previous approaches to produce...

Chemoenzymatic cascades are an important tool for advanced synthesis in chemistry. However, these often limited due to the incompatibility issue between two distinct catalysts and reactions. To address this issue, we present a simple multistep one-pot platform, which nanoparticle prepared allow chemo- biocatalytic reactions performed sequentially water Pickering emulsions. The preparation of pa...

The combination of small-molecule catalysis and enzyme represents an underexploited area research with huge potential in asymmetric synthetic chemistry due to both compatibility reaction conditions complementary reactivity. Herein, we describe the telescopic synthesis chiral nitro alcohols starting from commercially available benzaldehyde derivatives through one-pot three-step chemoenzymatic ca...