Opioid exit plans for tapering postoperative pain control in noncancer patients: a systematic review.

Background: A growing number of countries have reported sharp increases in the use and harm of opioid analgesics. High rates of new opioid initiation are observed in postoperative patients. In response, various tertiary care institutions have developed opioid exit plans (OEPs) to curb potential opioid-related harm.

An alternative broad-specificity pathway for glycan breakdown in bacteria.

The vast majority of glycosidases characterized to date follow one of the variations of the 'Koshland' mechanisms to hydrolyse glycosidic bonds through substitution reactions. Here we describe a large-scale screen of a human gut microbiome metagenomic library using an assay that selectively identifies non-Koshland glycosidase activities. Using this, we identify a cluster of enzymes with extremely broad substrate specificities and thoroughly characterize these, mechanistically and structurally.

Total Synthesis of Isoxeniolide A.

Isoxeniolide A is a highly strained xenicane diterpenoid of marine origin. This natural product is representative for a subfamily of xenicanes incorporating an allylic hydroxy group in the nine-membered ring; members of this xenicane subfamily so far have not been targeted by total synthesis. Herein, we describe the first asymmetric total synthesis of isoxeniolide A.

A Mechanism-Based Approach to Screening Metagenomic Libraries for Discovery of Unconventional Glycosidases.

Functional metagenomics has opened new opportunities for enzyme discovery. To exploit the full potential of this new tool, the design of selective screens is essential, especially when searching for rare enzymes. To identify novel glycosidases that employ cleavage strategies other than the conventional Koshland mechanisms, a suitable screen was needed.

Xenicane Natural Products: Biological Activity and Total Synthesis.

The xenicanes are a large class of mostly bicyclic marine diterpenoids featuring a cyclononane ring as a common structural denominator. After a brief introduction into the characteristic structural features of xenicanes and some biogenetic considerations, the major focus of this review will be on the various biological activities that have been reported for xenicanes and on efforts towards the total synthesis of these structures. Several xenicanes have been shown to be potent antiproliferative agents in vitro, but activities have also been reported in relation to inflammatory processes.

Total synthesis of (-)-zampanolide and structure-activity relationship studies on (-)-dactylolide derivatives.

A new total synthesis of the marine macrolide (-)-zampanolide (1) and the structurally and stereochemically related non-natural levorotatory enantiomer of (+)-dactylolide (2), that is, ent-2, has been developed. The synthesis features a high-yielding, selective intramolecular Horner-Wadsworth-Emmons (HWE) reaction to close the 20-membered macrolactone ring of 1 and ent-2. The β-keto phosphonate/aldehyde precursor for the ring-closure reaction was obtained by esterification of a ω-diethylphosphono carboxylic acid fragment and a secondary alcohol fragment incorporating the THP ring that is embedded in the macrocyclic core structure of 1 and ent-2.