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Photochemistry of mycolactone A/B and related unsaturated fatty acid esters is reported. On exposure to visible light, mycolactone A/B gave a mixture of four photomycolactones. Pentaenoates and tetraenoates, representing the unsaturated fatty acid portion of mycolactone A/B, were found to show the reactivity profile parallel with that of mycolactone A/B. The structure of the four photomycolactones was elucidated via (1) structure determination of the four photoproducts in the tetraenoate series; (2) their transformation to the photoproducts in the pentaenoate and then mycolactone series. Triplet quenchers did not affect the photochemical transformation, thereby indicating an event at the singlet state. A concerted, photochemically allowed [4πs + 2πa] cycloaddition was suggested to account for the observed result. This study provided the structurally defined and homogeneous material, which allowed demonstration that photomycolactones exhibit significantly reduced cytotoxicity, compared with mycolactone A/B. [ABSTRACT FROM AUTHOR]

The de novo asymmetric synthesis of cladospolides B and C and ( ENT)-cladospolide D has been achieved from achiral non-1-yne. The 11-13-step route relies upon a Noyori reduction and a KAPA promoted alkyne zipper reaction to relay an achiral functionality across a nine-carbon fragment and to enable the installation of a dienoate functionality. A diastereo- and regioselective Sharpless dihydroxylation of a dienoate installed the remaining stereochemistry. The de novo asymmetric route allowed for the asymmetric synthesis of three members of the cladospolide natural products and correctly established the structure for cladospolide D. [ABSTRACT FROM AUTHOR]

The enantioselective synthesis of cladospolide B, C, and (ent)-cladospolide Dhas been achieved in 11−15 steps from 1-nonyne. The route relies upon an alkyne zipper reaction to relay an ynone and dienoate functional groups across a nine carbon fragment, which enables a highly enantioselective Noyori ynone reduction and a diastereo- and regioselective Sharpless dihydroxylation of a dienoate. In addition to being a flexible approach to three members of the cladospolide natural products, this route for the first time correctly established the structure for cladospolide D. [ABSTRACT FROM AUTHOR]

Transgenerational epigenetic inheritance results from incomplete erasure of parental epigenetic marks during epigenetic reprogramming at fertilization. The significance of this phenomenon, and the mechanism by which it occurs, remains obscure. Here, we show that genetic mutations in Drosophila may cause epigenetic alterations that, when inherited, influence tumor susceptibility of the offspring. We found that many of the mutations that affected tumorigenesis induced by a hyperactive JAK kinase, HopTum-l, also modified the tumor phenotype epigenetically, such that the modification persisted even in the offspring that did not inherit the modifier mutation. We analyzed mutations of the transcription repressor Krüppel (Kr), which is one of the hopTum-l enhancers known to affect ftz transcription. We demonstrate that the Kr mutation causes increased DNA methylation in the ftz promoter region, and that the aberrant ftz transcription and promoter methylation are both transgenerationally heritable if HopTum-l is present in the oocyte. These results suggest that genetic mutations may alter epigenetic markings in the form of DNA methylation, which are normally erased early in the next generation, and that JAK overactivation disrupts epigenetic reprogramming and allows inheritance of epimutations that influence tumorigenesis in future generations. [ABSTRACT FROM AUTHOR]

NAD(P)H and NAD+ have a significant role in biochemistry, and many NAD(P)H models received particular attention. Research in NADH models mainly focuses on asymmetric reduction and life sciences. Over the past few decades, a particularly large number of new chiral NAD(P)H models have appeared, and there have been significant developments in this area. We summarized advanced research in chiral NAD(P)H models in this paper. These models not only show very good performance in asymmetric reduction, but also have excellent fluorescence features. In addition, we present a discussion about some recent studies on the asymmetric reduction of NAD(P)H-dependent dehydrogenase, and we open a new door on research into NAD(P)H models. At last, some advances focused on the fluorescence phenomenon of some chiral NAD(P)H models have also been summarized. 1 Introduction 2 NAD(P)H Models with Symmetric Structure 2.1 Chiral NAD(P)H Models with C 1 Symmetry 2.2 Chiral NAD(P)H Models with C 2 Symmetry 2.3 Chiral NAD(P)H Models with C 3 Symmetry 3 Symmetric Reduction 3.1 Effect of the Substituents of Dihydronicotinamide 3.2 Effect of the C-4 Substituent of Dihydropyridine 3.3 Special Structures 3.4 Applying Dehydrogenase to Biocatalytic Asymmetric Reductions with NADPH 4 Fluorescence Properties 5 Conclusion. [ABSTRACT FROM AUTHOR]

Transition-metal-catalyzed direct carbon-hydrogen bond functionalization has made significant advances in the field of carbon-hydrogen bond activation over the past decades. This methodology has the potential to be used in many different areas of chemistry; for example, it can provide an opportunity for the synthesis of various kinds of complex compounds. This account mainly focuses on recent advances in transition-metal-catalyzed direct sp3-carbon-hydrogen bond functionalization to form carbon-carbon bonds. 1 Introduction 2 Carbon-Carbon Bond Formation via Direct sp3-Carbon-Hydrogen Bond Functionalization 2.1 Coupling of sp3-Carbon-Hydrogen and sp-Carbon-Hydrogen Bonds 2.2 Coupling of sp3-Carbon-Hydrogen and sp2-Carbon-Hydrogen Bonds 2.3 Coupling of sp3-Carbon-Hydrogen and sp3-Carbon-Hydrogen Bonds 2.4 Coupling of sp3-Carbon-Hydrogen and C-X Bonds 3 Conclusion. [ABSTRACT FROM AUTHOR]

The polycomb repressive complex 2 (PRC2) histone methyltransferase plays a central role in epigenetic regulation in development and in cancer, and hence to interrogate its role in a specific developmental transition, methods are needed for disrupting function of the complex with high temporal and spatial precision. The catalytic and substrate recognition functions of PRC2 are coupled by binding of the N-terminal helix of the Ezh2 methylase to an extended groove on the EED trimethyl lysine binding subunit. Disrupting PRC2 function can in principle be achieved by blocking this single interaction, but there are few approaches for blocking specific protein-protein interactions in living cells and organisms. Here, we describe the computational design of proteins that bind to the EZH2 interaction site on EED with subnanomolar affinity in vitro and form tight and specific complexes with EED in living cells. Induction of the EED binding proteins abolishes H3K27 methylation in human embryonic stem cells (hESCs) and at all but the earliest stage blocks self-renewal, pinpointing the first critical repressive H3K27me3 marks in development. [ABSTRACT FROM AUTHOR]

A de novo asymmetric total synthesis of the macrolide natural product (S)-phoracantholide J has been achieved in 10 steps from the commodity chemicals (1-pentyne, ethyl acrylate, acetaldehyde, and hydrogen). The asymmetry of the route was introduced by a Noyori reduction of a 3-yn-2-one, which makes the route equally amenable to the synthesis of either enantiomer. In addition, this route relies upon an alkyne zipper, a hydroalkynylation, and a macrolactonization to complete the synthesis. [ABSTRACT FROM AUTHOR]

Introduction Mycobacterium ulcerans infection, known as Buruli ulcer, is a disease of the skin and subcutaneous tissues which is an important but neglected tropical disease with its major impact in rural parts of West and Central Africa where facilities for diagnosis and management are poorly developed. We evaluated fluorescent thin layer chromatography (f-TLC) for detection of mycolactone in the laboratory using samples from patients with Buruli ulcer and patients with similar lesions that gave a negative result on PCR for the IS2404 repeat sequence of M. ulcerans. Methodology/Principal findings Mycolactone and DNA extracts from fine needle aspiration (FNA), swabs and biopsy specimen were used to determine the sensitivity and specificity of f-TLC when compared with PCR for the IS2404. For 71 IS2404 PCR positive and 28 PCR negative samples the sensitivity was 73.2% and specificity of 85.7%for f-TLC. The sensitivity was similar for swabs (73%), FNAs (75%) and biopsies (70%). Conclusions We have shown that mycolactone can be detected from M. ulcerans infected skin tissue by f-TLC technique. The technique is simple, easy to perform and read with minimal costs. In this study it was undertaken by a member of the group from each endemic country. It is a potentially implementable tool at the district level after evaluation in larger field studies. [ABSTRACT FROM AUTHOR]

A novelcopper/manganese cocatalyzed direct oxidative couplingof terminal vinylarenes with ketones via C(sp3)–Hbond functionalization following C–C bond formation has beendeveloped using tert-butyl hydroperoxide as the radicalinitiator. Various ketones underwent a free-radical addition of terminalvinylarenes to give the corresponding 1,4-dicarbonyl products withexcellent regioselectivity and efficiency through one step. A possiblereaction mechanism has been proposed. [ABSTRACT FROM AUTHOR]

An efficient multi-component reaction to synthesize multi-substituted 1,3-oxazolidine compounds of high optical purity was described. All the products were well-characterized and the absolute configuration of one chiral center was determined. The plausible mechanism was proposed and a kinetic resolution of epoxides process was confirmed. [ABSTRACT FROM AUTHOR]