In 2005, the ACS Green Chemistry Institute (GCI) and the global pharmaceutical corporations developed the ACS GCI Pharmaceutical Roundtable to encourage the development of green chemistry and green engineering in the pharmaceutical industry. The Roundtable has established a list of key research areas including the direct nucleophilic reactions of alcohols. The substitution of activated alcohols is a frequently used approach for the preparation of active pharmaceutical ingredients. Alcohols are transformed into the reactive halides or sulfonate esters, thereby allowing their reaction with nucleophiles. Although the direct nucleophilic substitution of an alcohol should be an attractive process, as one of the byproducts from the reaction yields water, hydroxide is a poor leaving group that hinders the reaction. Recently, the direct substitution of allylic, benzylic, and tertiary alcohols has been achieved through an SN1 reaction with catalytic amounts of Brønsted or Lewis acids. In this review, the approaches leading to a greener process are examined in detail, and the advances achieved to date in this important transformation are presented.

Glucose is a major source of energy for most living organisms and its aberrant uptake is linked to many pathological conditions. However, our understanding of disease-associated glucose flux is limited due to the lack of robust tools. To date, positron emission tomography (PET) imaging remains the gold standard for measuring glucose uptake, and no optical tools exist for non-invasive longitudinal imaging of this important metabolite in in vivo settings. Here we report the development of a novel bioluminescent glucose uptake probe (BiGluc) for real-time, non-invasive longitudinal imaging of glucose absorption both in vitro and in vivo. In addition, we demonstrate that the sensitivity of our method is comparable with commonly used 18F-FDG-PET tracers and validate BiGluc as a tool for the identification of novel glucose transport inhibitors. The new imaging reagent enables a wide range of applications in the field of metabolism and drug development.

C-Glycosides represent an important class of bioactive compounds that are resistant to metabolic processing. 1,2 Although crosscoupling reactions are obvious approaches to these compounds, the sensitivity of C1-substituted organometallics to β-elimination processes (hydride or alkoxy) is the generally accepted reason why fully oxygenated and saturated structures are not typically accessible via these methods. [3][4][5] This notion is generally true of the synthetic methods that generate nucleophilic character at C1. 6 The contrastingly high number of methods for the synthesis of 2-deoxy C-glycosides 2a reinforces the notion of an elimination problem in C1 organometallics. 7 Recent investigations of pincer-ligated organometallic complexes

A novel Pd-catalyzed intramolecular allylic alkylation of indoles allows THBCs and THGCs to be effectively synthesized in high yields and excellent enantiomeric excesses (ee up to 97%).

Novel, clinically relevant, approaches to shift energy balance are urgently needed to combat metabolic disorders such as obesity and diabetes. One promising approach has been the expansion of brown adipose tissues that express uncoupling protein (UCP) 1 and thus can uncouple mitochondrial respiration from ATP synthesis. While expansion of UCP1-expressing adipose depots may be achieved in rodents via genetic and pharmacological manipulations or the transplantation of brown fat depots, these methods are difficult to use for human clinical intervention. We present a novel cell scaffold technology optimized to establish functional brown fat–like depots in vivo. We adapted the biophysical properties of hyaluronic acid–based hydrogels to support the differentiation of white adipose tissue–derived multipotent stem cells (ADMSCs) into lipid-accumulating, UCP1-expressing beige adipose tissue. Subcutaneous implantation of ADMSCs within optimized hydrogels resulted in the establishment of distinct UCP1-expressing implants that successfully attracted host vasculature and persisted for several weeks. Importantly, implant recipients demonstrated elevated core body temperature during cold challenges, enhanced respiration rates, improved glucose homeostasis, and reduced weight gain, demonstrating the therapeutic merit of this highly translatable approach. This novel approach is the first truly clinically translatable system to unlock the therapeutic potential of brown fat–like tissue expansion.