Synthesis of Oligosaccharides Designed to form Micelles,Corresponding to Structures Found in Ovarian Cyst Fluid

ABSTRACT

The syntheses of α-D-GlcpNAc-(1→4)-β-D-Galp-(1→4)-β-D-GlcNAc-(1→O)-(CH₂)₁₅CH₃ (1) and fragments thereof, corresponding to structures found in human ovarian cyst fluid, are described. Silver triflate promoted coupling of 3,4,6-tri-O-acetyl-2-azido-2-deoxy-β-D-glucopyranosyl bromide (12) and galactose acceptor (11) gave a disaccharide donor (13), which was readily transformed into the corresponding bromo-derivative 18. For the synthesis of disaccharide β-D-Galp-(1→4)-D-GlcNAc, several differently protected glucosamine acceptors were prepared. It was found that cetyl alcohol needed to be introduced after the formation of the β-galactoside bond. Glycosylation of pent-4-enyl 3,6-di-O-benzyl-2-deoxy-2-tetrachlorophthalimido-β-D-glucopyranoside (30) with (3,4,6-tri-O-acetyl-2-azido-2-deoxy-α-D-glucopyranosyl)-(1→4)-2,3,6-tri-O-benzoyl-α-D-galactopyranosyl bromide (18) by use of silver triflate as promoter gave the desired trisaccharide 31. Finally 31 was transformed via coupling to the long alkyl chain aglycon and deprotection into the title compound 1.     

Redox‐Switchable Ring‐Closing Metathesis: Catalyst Design,Synthesis, and Study

High yielding syntheses of 1‐(ferrocenylmethyl)‐3‐mesitylimidazolium iodide ( 1 ) and 1‐(ferrocenylmethyl)‐3‐mesitylimidazol‐2‐ylidene ( 2 ) were developed. Complexation of 2 to [{Ir(cod)Cl}₂] (cod=cis,cis‐1,5‐cyclooctadiene) or [Ru(PCy₃)Cl₂(?CH‐o‐O‐iPrC₆H₄)] (Cy=cyclohexyl) afforded 3 ([Ir( 2 )(cod)Cl]) and 5 ([Ru( 2 )Cl₂(?CH‐o‐O‐iPrC₆H₄)]), respectively. Complex 4 ([Ir( 2 )(CO)₂Cl]) was obtained by bubbling carbon monoxide through a solution of 3 in CH₂Cl₂. Spectroelectrochemical IR analysis of 4 revealed that the oxidation of the ferrocene moiety in 2 significantly reduced the electron‐donating ability of the N‐heterocyclic carbene ligand (ΔTEP=9 cm^?1; TEP=Tolman electronic parameter). The oxidation of 5 with [Fe(η⁵‐C₅H₄COMe)Cp][BF₄] as well as the subsequent reduction of the corresponding product [ 5 ][BF₄] with decamethylferrocene (Fc*) each proceeded in greater than 95 % yield. Mössbauer, UV/Vis and EPR spectroscopy analysis confirmed that [ 5 ][BF₄] contained a ferrocenium species, indicating that the iron center was selectively oxidized over the ruthenium center. Complexes 5 and [ 5 ][BF₄] were found to catalyze the ring‐closing metathesis (RCM) of diethyl diallylmalonate with observed pseudo‐first‐order rate constants (k_obs) of 3.1×10^?4 and 1.2×10^?5 s^?1, respectively. By adding suitable oxidants or reductants over the course of a RCM reaction, complex 5 was switched between different states of catalytic activity. A second‐generation N‐heterocyclic carbene that featured a 1′,2′,3′,4′,5′‐ pentamethylferrocenyl moiety ( 10 ) was also prepared and metal complexes containing this ligand were found to undergo iron‐centered oxidations at lower potentials than analogous complexes supported by 2 (0.30–0.36 V vs. 0.56–0.62 V, respectively). Redox switching experiments using [Ru( 10 )Cl₂(?CH‐o‐O‐iPrC₆H₄)] revealed that greater than 94 % of the initial catalytic activity was restored after an oxidation–reduction cycle.     

A Molecular modeling study of the changes of some steric properties of the precatalysts during the olefin metathesis reaction

The productive self‐metathesis of 1‐octene with a series of new phosphine ligated Grubbs‐type precatalysts was studied. The resulting structures were used to compare some steric properties of the new precatalysts with those of well‐known precatalysts. The possibility of α‐CC agnostic stabilization as well as the ability of the ligands to shield the metal was studied. A comparison of the obtained data, pointed to the unlikelihood that α‐CC agostic stabilization is a major contribution to the stabilization of the various metallacyclobutane rings. The similarity in the ability of the ligands to shield the metal also raised questions about the comparison of experimentally observed trends with those obtained theoretically. © 2014 Wiley Periodicals, Inc.     

The Varied Frustrated Lewis Pair Reactivity of the Germylene Phosphaketene (CH{(CMe)(2,6-iPr2C6H3N)}2)GePCO

The germylene species (CH{(CMe)(2,6-iPr₂C₆H₃N)}₂)GePCO 1 is shown to react with the Lewis acids (E(C₆F₅)₃ E=B, Al). Nonetheless, 1 participates in FLP chemistry with electron deficient alkynes or olefins, acting as an intramolecular FLP. In contrast, in the presence of B(C₆F₅)₃ and an electron rich alkyne, 1 behaves as Ge-based nucleophile to effect intermolecular FLP addition to the alkyne. This reactivity demonstrates that the reaction pathway is controlled by the nature of the electrophile and nucleophile generated in solution, as revealed by extensive DFT calculations.     

Control of pore environment in highly porous carbon materials for C2H6/C2H4 separation with exceptional ethane uptake

Adsorptive separation of C₂H₆ from C₂H₄ by adsorbents is an energy-efficient and promising method to boost the polymer grades C₂H₄ production. However, that C₂H₆ and C₂H₄ display very similar physical properties, making their separation extremely challenging. In this work, by regulating the pore environment in a family of chitosan-based carbon materials (C-CTS-1, C-CTS-2, C-CTS-4, and C-CTS-6)- we target ultrahigh C₂H₆ uptake and C₂H₆/C₂H₄ separation, which exceeds most benchmark carbon materials. Explicitly, the C₂H₆ uptake of C-CTS-2 (166 cm³/g at 100 kPa and 298 K) has the second-highest adsorption capacity among all the porous materials. In addition, C-CTS-2 gives C₂H₆/C₂H₄ selectivity of 1.75 toward a 1:15 mixture of C₂H₆/C₂H₄. Notably, the adsorption enthalpies for C₂H₆ in C-CTS-2 are low (21.3 kJ/mol), which will facilitate regeneration in mild conditions. Furthermore, C₂H₆/C₂H₄ separation performance was confirmed by binary breakthrough experiments. Under different ethane/ethylene ratios, C-CTS-X extracts a low ethane concentration from an ethane/ethylene mixture and produces high-purity C₂H₄ in one step. Spectroscopic measurement and diffraction analysis provide critical insight into the adsorption/separation mechanism. The nitrogen functional groups on the surface play a vital role in improving C₂H₆/C₂H₄ selectivity, and the adsorption capacities depend on the pore size and micropore volume. Moreover, these robust porous materials exhibit outstanding stability (up to 800 °C) and can be easily prepared on a large scale (kg) at a low cost (～$26 per kg), which is very significant for potential industrial applications.     

A Simple Homoleptic Gallium(I) Olefin Complex: Mimicking Transition‐Metal Chemistry at a Main‐Group Metal?

The earth‐metal olefin complex [Ga ^I (COD)₂]⁺[Al(OR^F)₄]^? (COD=1,5‐cyclooctadiene; R^F=C(CF₃)₃) constitutes the first homoleptic olefin complex of any main‐group metal accessible as a bulk compound. It is straight forward to prepare in good yield and constitutes an olefin complex of a main‐group metal that—similar to many transition‐metals—may adopt the +1 and +3 oxidation states opening potential applications. Crystallographic‐, vibrational‐ and computational investigations give an insight to the atypical bonding between an olefin and a main‐group metal. They are compared to classical transition‐metal relatives.     

Synthesis and Antiviral Evaluation of (1,4-Disubstituted-1,2,3-Triazol)-(E)-2-Methyl-but-2-Enyl Nucleoside Phosphonate Prodrugs

A series of hitherto unknown (1,4-disubstituted-1,2,3-triazol)-(E)-2-methyl-but-2-enyl nucleosides phosphonate prodrugs bearing 4-substituted-1,2,3-triazoles were prepared in a straight approach through an olefin acyclic cross metathesis as the key synthetic step. All novel compounds were evaluated for their antiviral activities against HBV, HIV and SARS-CoV-2. Among these molecules, only compound 15j, a hexadecyloxypropyl (HDP)/(isopropyloxycarbonyl-oxymethyl)-ester (POC) prodrug, showed activity against HBV in Huh7 cell cultures with 62% inhibition at 10 μM, without significant cytotoxicity (IC₅₀ = 66.4 μM in HepG2 cells, IC₅₀ = 43.1 μM in HepG2 cells) at 10 μM.     

Isoselective Ring-opening Polymerization of Racemic Lactide Catalyzed by N-heterocyclic Olefin/(Thio)urea Organocatalysts

The isoselective ring-opening polymerization of racemic lactide was achieved by combining N-heterocyclic olefin(NHO) with mono(thio)ureas or bis(thio)ureas as catalytic systems. The polymerization process shows high stereoselectivity, controllability and reactivity,delivering multi-block isotactic polylactides with high chain-end fidelity and narrow molecular weight distributions. The enhancement of catalytic performance was observed in the following order: bisthiourea(DTU) monothiourea(TU) bisurea(DU) urea(U). The highest Pm(probability of forming a meso dyad) = 0.91 was observed at-70 °C when using NHO/U1 catalytic system and the high stereoselectivity was attributed to chain-end control mechanism.     

Extended X‐ray absorption fine structure and multiple‐scattering simulation of nickel dithiolene complexes Ni[S2C2(CF3)2]2n (n = −2, −1, 0) and an olefin adduct Ni[S2C2(CF3)2]2(1‐hexene)

A series of Ni dithiolene complexes Ni[S₂C₂(CF₃)]₂ⁿ (n = ?2, ?1, 0) ( 1 , 2 , 3 ) and a 1‐hexene adduct Ni[S₂C₂(CF₃)₂]₂(C₆H₁₂) ( 4 ) have been examined by Ni K‐edge X‐ray absorption near‐edge structure (XANES) and extended X‐ray absorption fine‐structure (EXAFS) spectroscopies. Ni XANES for 1 – 3 reveals clear pre‐edge features and approximately +0.7 eV shift in the Ni K‐edge position for `one‐electron' oxidation. EXAFS simulation shows that the Ni—S bond distances for 1 , 2 and 3 (2.11–2.16 Å) are within the typical values for square planar complexes and decrease by ～0.022 Å for each `one‐electron' oxidation. The changes in Ni K‐edge energy positions and Ni—S distances are consistent with the `non‐innocent' character of the dithiolene ligand. The Ni—C interactions at ～3.0 Å are analyzed and the multiple‐scattering parameters are also determined, leading to a better simulation for the overall EXAFS spectra. The 1‐hexene adduct 4 presents no pre‐edge feature, and its Ni K‐edge position shifts by ?0.8 eV in comparison with its starting dithiolene complex 3 . Consistently, EXAFS also showed that the Ni—S distances in 4 elongate by ～0.046 Å in comparison with 3 . The evidence confirms that the neutral complex is `reduced' upon addition of olefin, presumably by olefin donating the π‐electron density to the LUMO of 3 as suggested by UV/visible spectroscopy in the literature.