Herein we describe a novel, hollow-structured zeolitic imidazolate framework (ZIF-8-H) nanosphere as a highly efficient catalyst for [3+3] cycloaddition reactions. The programmed installation of acidic Zn(2+) species and basic imidazolate moieties creates a synergistic catalytic system. Appropriate positioning of these functionalities in the catalytic system makes it possible to bring two substrates into close proximity and activate them cooperatively. Moreover, the flexible shell and the surface mesopores of ZIF-8-H provide the capacity for favorable binding of various sized substrates, stabilizing intermediates via their multiple force networks and the increased accessibility of the active sites. These features render ZIF-8-H a more highly active promoter than its homogeneous precursors, bulk ZIF-8 and ZIF-8-N nanoparticles. Finally, the robust catalyst can be easily recovered and reused 10 times without loss of catalytic activity.

Inflammation is a prominent pathological feature in pulmonary arterial hypertension, as demonstrated by pulmonary vascular infiltration of inflammatory cells, including T and B lymphocytes. However, the contribution of the adaptive immune system is not well characterized in pulmonary hypertension caused by chronic hypoxia. CD4 T cells are required for initiating and maintaining inflammation, suggesting that these cells could play an important role in the pathogenesis of hypoxic pulmonary hypertension. Our objective was to test the hypothesis that CD4 T cells, specifically the T helper 17 subset, contribute to chronic hypoxia-induced pulmonary hypertension. We compared indices of pulmonary hypertension resulting from chronic hypoxia (3 wk) in wild-type mice and recombination-activating gene 1 knockout mice (RAG1, lacking mature T and B cells). Separate sets of mice were adoptively transferred with CD4, CD8, or T helper 17 cells before normoxic or chronic hypoxic exposure to evaluate the involvement of specific T cell subsets. RAG1 mice had diminished right ventricular systolic pressure and arterial remodeling compared with wild-type mice exposed to chronic hypoxia. Adoptive transfer of CD4 but not CD8 T cells restored the hypertensive phenotype in RAG1 mice. Interestingly, RAG1 mice receiving T helper 17 cells displayed evidence of pulmonary hypertension independent of chronic hypoxia. Supporting our hypothesis, depletion of CD4 cells or treatment with SR1001, an inhibitor of T helper 17 cell development, prevented increased pressure and remodeling responses to chronic hypoxia. We conclude that T helper 17 cells play a key role in the development of chronic hypoxia-induced pulmonary hypertension.

An approach for efficient synthesis of Cglycosyl amino acids is described. Different from typical photoredox-catalyzed reactions of imines, the new process follows a pathway in which α-imino esters serve as electrophiles in chemoselective addition reactions with nucleophilic glycosyl radicals. The process is highlighted by the mild nature of the reaction conditions, the highly stereoselectivity attending C−C bond formation, and its applicability to C-glycosylations using both armed and disarmed pentose and hexose derivatives.C-Glycosyl amino acids are a unique class of compounds widely present in nature that have an enormously diverse array of biological properties. 1 Notable examples of substances in this family include the peptidyl nucleoside antibiotics amipurimycin, polyoxins, and nikkomycin, which have potent antimycotic activities against various human pathogenic fungi and bacteria (Scheme 1A). 2,3 More pronounced impacts of Cglycosyl amino acids arise from their broad application in biomedical and drug discovery studies of glycopeptides and proteins. 4,5 Finally, the presence of C−C linkages to anomeric centers gives members of this family higher metabolic stabilities and lipophilicities than those of O−C bondcontaining counterparts. In many instances, this feature leads to improved biological activities, membrane permeabilities, and bioavailabilities. 4,5 In routes developed to date for the synthesis of C-glycosyl amino acids, installation of an amino acid moiety onto a glycosyl framework has relied on the use of well-established αamino acid synthesis strategies, such as alkylation of α-amino acid equivalents, Strecker reactions, hydrogenation of dehydroamino acids, and multicomponent Ugi reactions with sugar derivatives (Scheme 1B). 6 In addition, de novo synthesis of Cglycosyl amino acids has been shown to be a viable approach to access unnatural substances in this family. Although often reliable, these polar bond disconnection based methods are inherently limited by a number of factors including the need for lengthy synthetic sequences, harsh reaction conditions, and/or a limited substrate scope. 7 As part of a recent program to develop radical-based crosscoupling processes for selective C−C bond formation, 8 we envisaged that an open-shell pathway might be applicable to the concise synthesis of C-glycosyl amino acids under mild conditions. 9,10 Specifically, we believed that addition of glycosyl radicals, generated from appropriate glycosyl pre-cursors, to readily available α-imino esters would constitute a viable approach to the preparation of these substances (Scheme 1C). To our knowledge, a strategy of this type has

A mild, versatile organophotoredox protocol has been developed for the preparation of diverse, enantioenriched α-deuterated α-amino acids. Distinct from the well-established two-electron transformations, this radical-based strategy offers the unrivaled capacity of the convergent unification of readily accessible feedstock carboxylic acids and a chiral methyleneoxazolidinone fragment and the simultaneous highly diastereo-, chemo-, and regioselective incorporation of deuterium. Furthermore, the approach has addressed the long-standing challenge of the installation of sterically demanding side chains into α-amino acids.