Progress toward the Synthesis of the Basiliolides and Transtaganolides: An Intramolecular Pyrone Diels−Alder Entry into a Novel Class of Natural Products

Efforts directed toward the synthesis of a basiliolide/transtaganolide model system are disclosed. A highly endo-selective intramolecular pyrone Diels−Alder (IMPDA) cycloaddition rapidly constructs the tricyclic core of the basiliolides and transtaganolides

Total Syntheses of (-)-Transtaganolide A, (+)-Transtaganolide B, (+)-Transtaganolide C, and (-)-Transtaganolide D and Biosynthetic Implications

‘Dibal'lin’ on a budget: The enantioselective total syntheses of transtaganolides A–D are rapidly achieved by a highly diastereoselective Ireland–Claisen/Diels–Alder cascade reaction of an enantioenriched geraniol derivative (see scheme). Based on X-ray diffraction data, the absolute configuration of these metabolites is established and discussed within the context of existing biosynthetic hypotheses

Unraveling the Electrical and Magnetic Properties of Layered Conductive Metal-Organic Framework With Atomic Precision

This paper describes structural elucidation of a layered conductive metal-organic framework (MOF) material Cu3(C6O6)2 by microcrystal electron diffraction with sub-angstrom precision. This insight enables the first identification of an unusual π-stacking interaction in a layered MOF material characterized by an extremely short (2.73 Å) close packing of the ligand arising from pancake bonding and ordered water clusters within pores. Band structure analysis suggests semiconductive properties of the MOF, which are likely related to the localized nature of pancake bonds and the formation of a singlet dimer of the ligand. The spin of CuII within the Kagomé arrangement dominates the paramagnetism of the MOF, leading to strong geometrical magnetic frustration

Conductive Stimuli-Responsive Coordination Network Linked with Bismuth for Chemiresistive Gas Sensing

This paper describes the design, synthesis, characterization, and performance of a novel semiconductive crystalline coordination network, synthesized using 2,3,6,7,10,11-hexahydroxytriphenylene (HHTP) ligands interconnected with bismuth ions, toward chemiresistive gas sensing. Bi(HHTP) exhibits two distinct structures upon hydration and dehydration of the pores within the network, Bi(HHTP)-α and Bi(HHTP)-β, respectively, both with unprecedented network topology (2,3-c and 3,4,4,5-c nodal net stoichiometry, respectively) and unique corrugated coordination geometries of HHTP molecules held together by bismuth ions, as revealed by a crystal structure resolved via microelectron diffraction (MicroED) (1.00 Å resolution). Good electrical conductivity (5.3 × 10–3 S·cm–1) promotes the utility of this material in the chemical sensing of gases (NH3 and NO) and volatile organic compounds (VOCs: acetone, ethanol, methanol, and isopropanol). The chemiresistive sensing of NO and NH3 using Bi(HHTP) exhibits limits of detection 0.15 and 0.29 parts per million (ppm), respectively, at low driving voltages (0.1–1.0 V) and operation at room temperature. This material is also capable of exhibiting unique and distinct responses to VOCs at ppm concentrations. Spectroscopic assessment via X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopic methods (i.e., attenuated total reflectance-infrared spectroscopy (ATR-IR) and diffuse reflectance infrared Fourier transformed spectroscopy (DRIFTS)), suggests that the sensing mechanisms of Bi(HHTP) to VOCs, NO, and NH3 comprise a complex combination of steric, electronic, and protic properties of the targeted analytes

The Total Syntheses of Basiliolide C, epi-Basiliolide C, and Protecting-Group-Free Total Syntheses of Transtaganolides C and D

The total syntheses of basiliolide C and previously unreported epi-basiliolide C are achieved by an Ireland–Claisen/Diels–Alder cascade. The development of a palladium catalyzed cross-coupling of methoxy alkynyl zinc reagents allows for the protecting-group-free syntheses of transtaganolides C and D. Syntheses of transtaganolides C and D are accomplished in a single operation to generate three rings, two all-carbon quaternary centers, and four tertiary stereocenters from a monocyclic, achiral precursor

Selective Nucleic Acid Capture with Shielded Covalent Probes

Nucleic acid probes are used for diverse applications in vitro, in situ, and in vivo. In any setting, their power is limited by imperfect selectivity (binding of undesired targets) and incomplete affinity (binding is reversible, and not all desired targets bound). These difficulties are fundamental, stemming from reliance on base pairing to provide both selectivity and affinity. Shielded covalent (SC) probes eliminate the longstanding trade-off between selectivity and durable target capture, achieving selectivity via programmable base pairing and molecular conformation change, and durable target capture via activatable covalent cross-linking. In pure and mixed samples, SC probes covalently capture complementary DNA or RNA oligo targets and reject two-nucleotide mismatched targets with near-quantitative yields at room temperature, achieving discrimination ratios of 2–3 orders of magnitude. Semiquantitative studies with full-length mRNA targets demonstrate selective covalent capture comparable to that for RNA oligo targets. Single-nucleotide DNA or RNA mismatches, including nearly isoenergetic RNA wobble pairs, can be efficiently rejected with discrimination ratios of 1–2 orders of magnitude. Covalent capture yields appear consistent with the thermodynamics of probe/target hybridization, facilitating rational probe design. If desired, cross-links can be reversed to release the target after capture. In contrast to existing probe chemistries, SC probes achieve the high sequence selectivity of a structured probe, yet durably retain their targets even under denaturing conditions. This previously incompatible combination of properties suggests diverse applications based on selective and stable binding of nucleic acid targets under conditions where base-pairing is disrupted (e.g., by stringent washes in vitro or in situ, or by enzymes in vivo)

The CryoEM Method MicroED as a Powerful Tool for Small Molecule Structure Determination

In the many scientific endeavors that are driven by organic chemistry, unambiguous identification of small molecules is of paramount importance. Over the past 50 years, NMR and other powerful spectroscopic techniques have been developed to address this challenge. While almost all of these techniques rely on inference of connectivity, the unambiguous determination of a small molecule’s structure requires X-ray and/or neutron diffraction studies. In practice, however, X-ray crystallography is rarely applied in routine organic chemistry due to intrinsic limitations of both the analytes and the technique. Here we report the use of the electron cryo-microscopy (cryoEM) method microcrystal electron diffraction (MicroED) to provide routine and unambiguous structural determination of small organic molecules. From simple powders, with minimal sample preparation, we could collect high-quality MicroED data from nanocrystals (∼100 nm, ∼10^(–15) g) resulting in atomic resolution (<1 Å) crystal structures in minutes

Regulating Transition‐Metal Catalysis through Interference by Short RNAs

Herein we report the discovery of a Au^I–DNA hybrid catalyst that is compatible with biological media and whose reactivity can be regulated by small complementary nucleic acid sequences. The development of this catalytic system was enabled by the discovery of a novel Au^I-mediated base pair. We found that Au^I binds DNA containing C-T mismatches. In the Au^I–DNA catalyst's latent state, the Au^I ion is sequestered by the mismatch such that it is coordinatively saturated, rendering it catalytically inactive. Upon addition of an RNA or DNA strand that is complementary to the latent catalyst's oligonucleotide backbone, catalytic activity is induced, leading to a sevenfold increase in the formation of a fluorescent product, forged through a Au^I-catalyzed hydroamination reaction. Further development of this catalytic system will expand not only the chemical space available to synthetic biological systems but also allow for temporal and spatial control of transition-metal catalysis through gene transcription