Total Synthesis of Clerobungin A via a Cascade Cyclization Reaction

The first total synthesis of the novel cyclohexylethanoid natural product clerobungin A has been achieved in six steps and 14% overall yield starting from commercially available tyrosol. Key steps in this sequence include a bioinspired oxidative dearomatization of a phenol and a hemiacetalization/oxa-Michael cascade to form the tricyclic ring system. Resolution of a late-stage intermediate via chiral HPLC allowed for the measurement of the chiroptical properties of both enantiomers of clerobungin A, supporting the scalemic nature of the natural product

Total Synthesis of Pyrophen and Campyrones A–C

The first total syntheses of the natural products pyrophen and campyrones A–C, isolated from the fungus <i>Aspergillus niger</i>, have been achieved in six steps starting from commercially available <i>N</i>-Boc amino acids. Key steps in this sequence include a vinylogous Claisen condensation to achieve fragment coupling and a dioxinone thermolysis/cyclization cascade to form the α-pyrone ring. The route described herein afforded the natural products in 15–25% overall yield, furnishing sufficient material for testing in biological assays

Microbial Biotransformation Products and Pathways of Dichloroacetamide Herbicide Safeners

Dichloroacetamide safeners are common ingredients in commercial herbicide formulations. We previously investigated the environmental fate of dichloroacetamides via photolysis and hydrolysis, but other potentially important, environmentally relevant fate processes remain uncharacterized and may yield products of concern. Here, we examined microbial biotransformation of two dichloroacetamide safeners, benoxacor and dichlormid, to identify products and elucidate pathways. Using aerobic microcosms inoculated with river sediment, we demonstrated that microbial biotransformations of benoxacor and dichlormid proceed primarily, if not exclusively, via cometabolism. Benoxacor was transformed by both hydrolysis and microbial biotransformation processes; in most cases, biotransformation rates were faster than hydrolysis rates. We identified multiple novel products of benoxacor and dichlormid not previously observed for microbial processes, with several products similar to those reported for structurally related chloroacetamide herbicides, thus indicating potential for conserved biotransformation mechanisms across both chemical classes. Observed products include monochlorinated species such as the banned herbicide CDAA (from dichlormid), glutathione conjugates, and sulfur-containing species. We propose a transformation pathway wherein benoxacor and dichlormid are first dechlorinated, likely via microbial hydrolysis, and subsequently conjugated with glutathione. This is the first study reporting biological dechlorination of dichloroacetamides to yield monochlorinated products in aerobic environments