Divergent Synthesis of Bioactive Dithiodiketopiperazine Natural Products Based on a Double C(sp3)−H Activation Strategy

This article provides a detailed report of our efforts to synthesize the dithiodiketopiperazine (DTP) natural products (−)-epicoccin G and (−)-rostratin A using a double C(sp³)−H activation strategy. The strategy's viability was first established on a model system lacking the C8/C8’ alcohols. Then, an efficient stereoselective route including an organocatalytic epoxidation was secured to access a key bis-triflate substrate. This bis-triflate served as the functional handles for the key transformation of the synthesis: a double C(sp³)−H activation. The successful double activation opened access to a common intermediate for both natural products in high overall yield and on a multigram scale. After several unsuccessful attempts, this intermediate was efficiently converted to (−)-epicoccin G and to the more challenging (−)-rostratin A via suitable oxidation/reduction and protecting group sequences, and via a final sulfuration that occurred in good yield and high diastereoselectivity. These efforts culminated in the synthesis of (−)-epicoccin G and (−)-rostratin A in high overall yields (19.6 % over 14 steps and 12.7 % over 17 steps, respectively), with the latter being obtained on a 500 mg scale. Toxicity assessments of these natural products and several analogues (including the newly synthesized epicoccin K) in the leukemia cell line K562 confirmed the importance of the disulfide bridge for activity and identified dianhydrorostratin A as a 20x more potent analogue.     

Chiral Ru-based complexes for asymmetric olefin metathesis: enhancement of catalyst activity through steric and electronic modifications

Design, synthesis, characterization, and catalytic activity of six enantiomerically pure Ru-based metathesis catalysts are disclosed (3a-3f). The new chiral catalysts were prepared through steric and electronic alterations of the parent catalyst system (3). The present studies indicate that the effect of structural modifications of chiral complex 3 does not always correspond to those of the related achiral complexes. The present findings illustrate that modified Ru complexes (3e and 3f) deliver reactivity levels that are more than 2 orders of magnitude higher than 3. Reactivity and physical data are provided that shed light on the origin of activity differences. Some members of the new generation of chiral Ru catalysts promote asymmetric ring-opening (AROM) and ring-closing (ARCM) metatheses that cannot be effected by the first generation chiral catalyst (3).     

Effect of Pr-Ca substitution on the transport and magnetic behavior of LaMnO3 perovskite

The effect of simultaneous substitution of a fluctuating cation and a divalent cation in LaMnO₃ perovskite modifies the properties of the material to exhibit large valence colossal magnetoresistance (CMR) effect. A good example of these properties is (La_1−2x Pr _x Ca _x )MnO₃ (LPCMO) type CMR material. In this communication it is reported that, with the increase in x (for x=0.1, 0.15, 0.2), the T _c varies between 100 and 120 K with improvisation in metal-insulator transition. Interestingly, resistance increases with x from few hundred ohms to few kilo ohms with corresponding decrease in the unit cell volume. The results of the studies using X-ray diffraction (XRD), electrical resistivity, magnetoresistance and ac susceptibility measurements on LPCMO samples for understanding the structural, transport and magnetic properties are discussed in detail.     

Nanopore Sequencing Accurately Identifies the Mutagenic DNA Lesion O6‐Carboxymethyl Guanine and Reveals Its Behavior in Replication

O⁶‐carboxymethylguanine (O⁶‐CMG) is a highly mutagenic alkylation product of DNA, triggering transition mutations relevant to gastrointestinal cancer. However, precise localization of a single O⁶‐CMG with conventional sequencing platforms is challenging. Here nanopore sequencing (NPS), which directly senses single DNA bases according to their physiochemical properties, was employed to detect O⁶‐CMG. A unique O⁶‐CMG signal was observed during NPS and a single‐event call accuracy of >95 % was achieved. Moreover, O⁶‐CMG was found to be a replication obstacle for Phi29 DNA polymerase (Phi29 DNAP), suggesting this lesion could cause DNA sequencing biases in next generation sequencing (NGS) approaches.     

Das Atomgewicht von Stickstoff und Arsen

Ohne Zusammenfassung     

The putative Diels-Alderase macrophomate synthase is an efficient aldolase

We find that the putative Diels-Alderase macrophomate synthase (MPS) catalyzes the addition of pyruvate enolate, generated by decarboxylation of oxaloacetate, to a variety of aldehydes. Alkyl, aryl, and heteroaryl aldehydes are accepted as substrates, providing gamma-hydroxy-alpha-ketoacids in 35-95% yield with modest levels of stereochemical control. These aldol products, which are difficult to synthesize by other methods, are formed with efficiency comparable to that of macrophomate. Our results thus provide evidence that a two-step Michael-aldol pathway is a plausible alternative to the postulated [4 + 2] cycloaddition in the MPS-catalyzed addition of pyruvate enolate to 2-pyrones. They are also relevant to understanding the divergent evolution of type II pyruvate aldolases.     

Ru complexes bearing bidentate carbenes: from innocent curiosity to uniquely effective catalysts for olefin metathesis

The discovery and development of a new class of Ru-based catalysts for olefin metathesis is described. These catalysts, particularly those that do not bear a phosphine ligand, have been demonstrated to promote unique levels of reactivity in a variety of olefin metathesis reactions. The design and development of supported and chiral optically pure variants of this class of Ru catalysts for use in enantioselective metathesis are discussed as well. All catalysts are air stable, reusable, and can be employed with unpurified solvents.     

关于K个复相关矩阵相等的检验

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Synthesis of Various Water Soluble and Stable Copper Complexes Bearing N‐Heterocyclic Carbene Ligands and Their Activity in DNA Alkylation

We report here the synthesis and catalytic evaluation in DNA alkylation of a series of water‐soluble copper complexes bearing N‐heterocyclic carbene (NHC) ligands. The NHC ligands were chosen to cover the gamut of commonly used scaffold variations, but in many cases, copper complexes could not be obtained or were unstable. Nevertheless, we identified several complexes that were both stable and catalytically active. Our studies provide guidance and starting scaffolds for any researchers interested in aqueous copper(I) catalysis. A key practical aspect of our findings is that azide‐bearing copper‐NHC complexes are excellent substrates for the azide‐alkyne cycloaddition, which allows late‐stage tailoring of the copper complexes.