Studies Towards the Synthesis of the Core of Endiandric Acid H
In the presence of a CuBr·SMe2 catalytic system, a very simple and efficient approach for the synthesis of the key precursor of the core of endiandric acids starting from the readily and abundantly available 3-butyn-1-ol in five linear steps with an overall yield of 40% was developed.
Synthesis and biological evaluations of a series of calycanthaceous analogues as antifungal agents
Abstract Starting from indole-3-acetonitrile, a total of 66 new calycanthaceous alkaloid analogues were synthesised in excellent yields. The prepared compounds were evaluated for their biological activities against a broad range of plant pathogen fungi. The results of bioassays indicated that the majority of tested compounds displayed comparable or better in vitro bioactivities than the positive control. Notably, Compound a1 displayed a significant activities against B. cereus, Escherichia sp and R. solanacearum, even better than the positive control streptomycin and Penicillin, with the same MIC value of 15.63 µg mL−1. Compound a1 displayed a broad spectrum and remarkably activities among the tested calycanthaceous analogues and might be a novel potential leading compound for further development of antifungal agents. The results obtained in the study will be very helpful for further design and structural optimisation of calycanthaceous alkaloids as potential agrochemical lead for plant disease control. Graphical Abstract
Structure of class B GPCR corticotropin-releasing factor receptor 1
Structural analysis of class B G-protein-coupled receptors (GPCRs), cell-surface proteins that respond to peptide hormones, has been restricted to the amino-terminal extracellular domain, thus providing little understanding of the membrane-spanning signal transduction domain. The corticotropin-releasing factor receptor type 1 is a class B receptor which mediates the response to stress and has been considered a drug target for depression and anxiety. Here we report the crystal structure of the transmembrane domain of the human corticotropin-releasing factor receptor type 1 in complex with the small-molecule antagonist CP-376395. The structure provides detailed insight into the architecture of class B receptors. Atomic details of the interactions of the receptor with the non-peptide ligand that binds deep within the receptor are described. This structure provides a model for all class B GPCRs and may aid in the design of new small-molecule drugs for diseases of brain and metabolism.