Total Synthesis of Nominal Gobienine A

The lichen‐derived glycoconjugate gobienine A is structurally more complex than most glycolipids isolated from higher plants by virtue of the all‐cis substituted γ‐lactone substructure embedded into its macrocyclic frame. A concise entry into this very epimerization‐prone and hence challenging structural motif is presented, which relies on an enantioselective cyanohydrin formation, an intramolecular Blaise reaction, a palladium‐catalyzed alkoxycarbonylation, and a diastereoselective hydrogenation of the tetrasubstituted alkene in the resulting butenolide. This strategy, in combination with ring‐closing olefin metathesis for the formation of the macrocyclic perimeter, allowed the proposed structure of gobienine A ( 1 ) to be formed in high overall yield. The recorded spectral data show that the structure originally attributed to gobienine A is incorrect and that it is not the epimerization‐prone ester site on the butanolide ring that is the locus of misassignment; rather, the discrepancy must be more profound.     

Synthesis of Derivatives of 2,6-Dideoxy-2,2-Difluoro-3-O-Methyl-l-Arabinopyranose (2,2-Difluorooleandrose)

Abstract

L-Oleandrose is the carbohydrate constituent of the potent anthelmintic agents the avermectins. Diethylaminosulfur tri-fluoride treatment of appropriate uloses did not give gem-difluoro sugars. Trifluorofluoroxymethane or xenon difluoride addition to the double bond of 4-O-benzoyl-6-deoxy-2-fluoro-3-O-methyl-L-glucal produced protected 2,2-difluorooleandrose derivatives activated at their anomeric center and ready for glycosidation.     

Gold Carbenoids: Lessons Learnt from a Transmetalation Approach

Carbophilic catalysts that are based on Au^I allow a host of different nucleophiles to be added across various π systems. 1 – 3 Although many of these reactions are thought to proceed via gold carbenoids, the challenge to observe and characterize these putative intermediates has basically been unmet. 4 The current mechanistic interpretation therefore largely relies on indirect evidence and computational data, some of which are subject to debate. 5 In an attempt to fill this gap, we pursued a potential route to gold carbenoids by formal transmetalation of chromium or tungsten Fischer carbene complexes with [LAu]⁺. Whereas this transformation proceeds with exceptional ease as long as a stabilizing heteroelement is present on the carbene center, it stops half‐way in its absence. Rather unusual bimetallic arrays are formed, which allow the charge density to delocalize over several positions. The obvious difficulty of releasing an “unstabilized” gold carbenoid has potential mechanistic implications for the understanding of π‐acid catalysis in general.     

Cyclic‐Disulfide‐Based Prodrugs for Cytosol‐Specific Drug Delivery

The cytosolic conversion of therapeutically relevant nucleosides into bioactive triphosphates is often hampered by the inefficiency of the first kinase‐mediated step. Nucleoside monophosphate prodrugs can be used to bypass this limitation. Herein we describe a novel cyclic‐disulfide class of nucleoside monophosphate prodrugs with a cytosol‐specific, reductive release trigger. The key event, a charge‐dissipating reduction‐triggered cyclodeesterification leads to robust cytosolic production of the cyclic 3′,5′‐monophosphate for downstream enzymatic processing. The antiviral competence of the platform was demonstrated with an O‐benzyl‐1,2‐dithiane‐4,5‐diol ester of 2′‐C‐methyluridine‐3′,5′‐phosphate. Both in vitro and in vivo comparison with the clinically efficacious ProTide prodrug of 2′‐deoxy‐2′‐α‐fluoro‐β‐C‐methyluridine is provided. The cytosolic specificity of the release allows for a wide range of potential applications, from tissue‐targeted drug delivery to intracellular imaging.     

Mapping Platinum Species in Polymer Electrolyte Fuel Cells by Spatially Resolved XAFS Techniques

There is limited information on the mechanism for platinum oxidation and dissolution in Pt/C cathode catalyst layers of polymer electrolyte fuel cells (PEFCs) under the operating conditions though these issues should be uncovered for the development of next‐generation PEFCs. Pt species in Pt/C cathode catalyst layers are mapped by a XAFS (X‐ray absorption fine structure) method and by a quick‐XAFS(QXAFS) method. Information on the site‐preferential oxidation and leaching of Pt cathode nanoparticles around the cathode boundary and the micro‐crack in degraded PEFCs is provided, which is relevant to the origin and mechanism of PEFC degradation.     

Metal‐Free Catalyst for the Chemoselective Methylation of Amines Using Carbon Dioxide as a Carbon Source

N‐methylation of amines is an important step in the synthesis of many pharmaceuticals and has been widely applied in the preparation of other key intermediates and chemicals. Therefore, the development of efficient methylation methods has attracted considerable attention. In this respect, carbon dioxide is an attractive C₁ building block because it is an abundant, renewable, and nontoxic carbon source. Consequently, we developed a highly chemoselective, metal‐free catalytic system that operates under ambient conditions for the N‐methylation of amines.     

Design, synthesis, and characterization of a calcium-sensitive near infrared dye

Intracellular calcium concentration in biological cells varies from 0.1 to 10 μM depending upon cell signaling and disease states. A direct estimate of calcium concentration in cell tissues within this range is possible with a novel calcium-selective reagent 15C5-774. The molecule of 15C5-774 consists of a near-infrared (NIR) chromophore (λ_max=774 nm) and a metal complexing moiety of benzo-15-crown-5. The reagent shows a strong calcium binding affinity in a 1:1 ratio and metal selectivity in the order Ca²⁺>Mg²⁺>Sr²⁺≈K⁺≈Na⁺>Zn²⁺>Li⁺. The high sensitivity is achieved by conducting absorption measurements in the NIR region where background interference from the biological matrix is low.