1. Genistein-Derived ROS-Responsive Nanoparticles Relieve Colitis by Regulating Mucosal Homeostasis
Wentao Fan, Shuo Zhang, Yuting Wu, Tao Lu, Jiwen Liu, Xiuyun Cao, Shuhui Liu, Liping Yan, Xizhi Shi, Guangliang Liu, Chaobo Huang, Suquan Song ACS Appl Mater Interfaces. 2021 Sep 1;13(34):40249-40266. doi: 10.1021/acsami.1c09215. Epub 2021 Aug 23.
Disruption of intestinal homeostasis is an important event in the development of inflammatory bowel disease (IBD), and genistein (GEN) is a candidate medicine to prevent IBD. However, the clinical application of GEN is restricted owing to its low oral bioavailability. Herein, a reactive oxygen species (ROS)-responsive nanomaterial (defined as GEN-NP2) containing superoxidase dismutase-mimetic temporally conjugated β-cyclodextrin and 4-(hydroxymethyl)phenylboronic acid pinacol ester-modified GEN was prepared. GEN-NP2 effectively delivered GEN to the inflammation site and protected GEN from rapid metabolism and elimination in the gastrointestinal tract. In response to high ROS levels, GEN was site-specifically released and accumulated at inflammatory sites. Mechanistically, GEN-NP2 effectively increased the expression of estrogen receptor β (ERβ), simultaneously reduced the expression of proinflammatory mediators (apoptosis-associated speck-like protein containing a CARD (ASC) and Caspase1-p20), attenuated the infiltration of inflammatory cells, promoted autophagy of intestinal epithelial cells, inhibited the secretion of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), modulated the gut microbiota, and ultimately alleviated colitis. In addition, the oral administration of these nanoparticles showed excellent safety, thereby providing confidence in the further development of precise treatments for IBD.
2. Allenylboronic Acid Pinacol Ester: A Selective Partner for [4 + 2] Cycloadditions
Natalia Labadie, Juan M Ramos Marchena, Noelia S Medrán, Silvina C Pellegrinet Org Lett. 2021 Jul 2;23(13):5081-5085. doi: 10.1021/acs.orglett.1c01609. Epub 2021 Jun 21.
We have studied the reaction of allenylboronic acid pinacol ester with cyclopentadiene with experimental and computational methods. The reaction occurred efficiently with complete Diels-Alder periselectivity and regioselectivity at the proximal double bond. The concerted mechanism for the observed transformation was computed to be favored over competitive addition to the distal double bond, [3,3]-sigmatropic rearrangements, and stepwise radical mechanism. This unprecedented Diels-Alder reaction enables the construction of synthetically versatile boron-substituted cycloadducts.
3. Preparation of 3,4-Substituted-5-Aminopyrazoles and 4-Substituted-2-Aminothiazoles
Stepan Havel, Prashant Khirsariya, Naresh Akavaram, Kamil Paruch, Benoit Carbain J Org Chem. 2018 Dec 21;83(24):15380-15405. doi: 10.1021/acs.joc.8b02655. Epub 2018 Dec 6.
3,4-Substituted-5-aminopyrazoles and 4-substituted-2-aminothiazoles are frequently used intermediates in medicinal chemistry and drug discovery projects. We report an expedient flexible synthesis of 3,4-substituted-5-aminopyrazoles (35 examples), based on palladium-mediated α-arylation of β-ketonitriles with aryl bromides. A library of 4-substituted-2-aminothiazoles (21 examples) was assembled by a sequence employing Suzuki coupling of newly prepared, properly protected pinacol ester and MIDA ester of 4-boronic acid-2-aminothiazole with (hetero)aryl halides.
