Asymmetric Monoreduction of α,β-Dicarbonyls to α-Hydroxy Carbonyls by Ene Reductases.

Ene reductases (EREDs) catalyze asymmetric reduction with exquisite chemo-, stereo-, and regioselectivity. Recent discoveries led to unlocking other types of reactivities toward oxime reduction and reductive C-C bond formation. Exploring nontypical reactions can further expand the biocatalytic knowledgebase, and evidence alludes to yet another variant reaction where flavin mononucleotide (FMN)-bound ERs from the old yellow enzyme family (OYE) have unconventional activity with α,β-dicarbonyl substrates.

Peroxygenase-Catalyzed Allylic Oxidation Unlocks Telescoped Synthesis of (1,3)-3-Hydroxycyclohexanecarbonitrile.

The unmatched chemo-, regio-, and stereoselectivity of enzymes renders them powerful catalysts in the synthesis of chiral active pharmaceutical ingredients (APIs). Inspired by the discovery route toward the LPA-antagonist BMS-986278, access to the API building block (1,3)-3-hydroxycyclohexanecarbonitrile was envisaged using an ene reductase (ER) and alcohol dehydrogenase (ADH) to set both stereocenters. Starting from the commercially available cyclohexene-1-nitrile, a C-H oxyfunctionalization step was required to introduce the ketone functional group, yet several chemical allylic oxidation strategies proved unsuccessful.

Enantio-Complementary Synthesis of 2-Substituted Pyrrolidines and Piperidines via Transaminase-Triggered Cyclizations.

Chiral -heterocycles are a common motif in many active pharmaceutical ingredients; however, their synthesis often relies on the use of heavy metals. In recent years, several biocatalytic approaches have emerged to reach enantiopurity. Here, we describe the asymmetric synthesis of 2-substituted pyrrolidines and piperidines, starting from commercially available ω-chloroketones by using transaminases, which has not yet been comprehensively studied.

Influence of Multimodal Treatment on Rest/Activity and Autonomic Regulation in Breast Cancer Patients with Cancer-Related Fatigue: Results of a Tri-Centre Trial with a Comprehensive Cohort Design.

Introduction: Breast cancer patients with cancer-related fatigue (BC-CRF) often have lower physical activity. To investigate how this could be improved, we evaluated a multimodal treatment (MT) and a combination of MT with aerobic training (CT) and compared these with aerobic training (AT) regarding rest/activity rhythm and state autonomic regulation (State aR).

Methods: In this pragmatic comprehensive cohort design study, the explorative analysis focused on actigraphy and State aR including the rest/activity regulation subscale (State aR-R/A) which were assessed at baseline (T0), after 10 weeks of intervention (T1), and State aR additionally 6 months later (T2).