Synthesis of 1,3,4-Oxadiazoles by Iodine-mediated Oxidative Cyclization of Methyl Ketones with 4-Phenylsemicarbazide

An efficient one-pot method to access 5-amino-2-benzoyl-1,3,4-oxadiazoles via I2/DMSO promoted oxidative cyclization of 4-phenylsemicarbazide with (het)aryl methyl ketones under mild conditions was developed. This reaction proceeds smoothly with a wide range of methyl ketones containing different functional groups to give the corresponding products in moderate yields under mild conditions.

A One-pot Access to Diastereoselective Benzo[5,6]oxepino[2,3-c]pyrroles via Formal (5+2)-Annulation of Donor-/Acceptor-Type Aryl Vinyl diazosuccinimide with Ketones Under Silver Catalysis

A silver triflimide catalyzed one-pot protocol for the diastereoselective synthesis of dihydrobenzoxepines has been developed. Silver triflimide found to be an efficient catalyst for the formal (5+2)-cycloaddition to access dihydrobenzoxepines as a single diastereomer using vinyl diazo compounds as 5-C-synthons and ketones. An unmet challenge of utilizing the donor-/acceptor-type vinyl diazosuccinimides as 5-C-synthons under silver-catalysis is presented. This protocol found to be highly regio-, chemo- and diastereoselective, and works well with aliphatic as well as aromatic methyl ketones bearing electron deactivating as well as donating groups to afford dihydrobenzo[5,6]oxepino[2,3-c]pyrroles with a broad substrates scope. The control experiments and time dependent NMR studies revealed the plausible mechanism of this transformation. The protocol also proved to be scalable on the gram scale synthesis.

Metabolic engineering strategies to produce medium-chain oleochemicals via acyl-ACP:CoA transacylase activity

Microbial lipid metabolism is an attractive route for producing aliphatic chemicals, commonly referred to as oleochemicals. The predominant metabolic engineering strategy centers on heterologous thioesterases capable of producing fatty acids of desired size. To convert acids to desired oleochemicals (e.g. fatty alcohols, ketones), metabolic engineers modify cells to block beta-oxidation, reactivate fatty acids as coenzyme-A thioesters, and redirect flux towards termination enzymes with broad substrate utilization ability. These genetic modifications narrow the substrate pool available for the termination enzyme but cost one ATP per reactivation - an expense that could be saved if the acyl-chain was directly transferred from ACP- to CoA-thioester. In this work, we demonstrate an alternative acyl-transferase strategy for producing medium-chain oleochemicals. Through bioprospecting, mutagenesis, and metabolic engineering, we developed strains of Escherichia coli capable of producing over 1 g/L of medium-chain free fatty acids, fatty alcohols, and methyl ketones using the transacylase strategy.