Synthesis and application of an IL-supported diol as protecting group for aldehydes

A new IL-supported diol,1-(2,3-dihydroxypropyl)-3-methylimidazolium hexafluorophosphate has been synthesized and char- acterized by FT-IR,~1H NMR,~(13)C NMR and MS (ESI).Its physical properties such as freezing point,solubility and specific gravity and thermal stability were determined.Synthetic utilities of the resultant diol as a protecting group for aldehydes were also investigated.     

Chemistry on the Complex: Derivatization of TiO4N2-Based Complexes and Application to Multi-Step Synthesis

The chemistry on octahedral TiO₄N₂-complexes is described. The Ti(IV)-based precursors are composed of two 3,3’-diphenyl-2,2’-biphenolato ligands (1) and one substituted 1,10-phenanthroline ligand (2-5). The application of imine condensation, palladium-catalyzed C−C bond formation or copper-catalysed azide-alkyne cycloaddition allowed the grafting of various new groups onto these species. In particular Sonogashira reactions permitted to observe an excellent conversion of the starting complexes. This systematic study enabled to compile the factors required to preserve the framework of the complexes in the course of a chemical transformation. Thanks to this chemistry realized on the complex, the Ti(1)₂ fragment was used as a protecting group to develop a multi-step synthesis of a bis-phenanthroline compound (12), for which the synthesis without this protection failed. Thus, a dinuclear complex [Ti₂(1)₄(12)] was first prepared starting from complex precursor bearing an acetylenic function via a Hay coupling reaction. This was followed by a deprotection step affording 12. Overall, this work illustrates how the Ti(1)₂ fragment could be an useful tool for the preparation of unprecedented diimine compounds.     

Synthesis of spiro-substituted 1,3-oxazines by a new sequence leading to spiroheterocycles

Summary The target compounds, i.e. 1,3-oxazines which are spiro-substituted in position 6 by a piperidine moiety, are derived from 1-oxa-3,9-diaza-spiro[5.5]undecane, a novel heterocyclic parent system. They were all approached by the following three-step sequence: 1,3-dipolar cycloadditions of nitrile oxides and nitrones to piperidines bearing an exocyclic methylene group gave the corresponding spiro-substituted oxazole derivatives3. In a consecutive step these were cleaved by hydrogenolysis to -amino-alcohols4, which in a final step were recyclized by insertions of a C₁-unit to yield the target structures5–10: thus ade facto ring-extension of spiro-oxazoles to spiro-oxazines was accomplished.

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Synthese von spirosubstituierten 1,3-Oxazinen mittels einer neuen zu Spiroheterocyclen führenden Synthesefolge

Zusammenfassung Die Zielverbindungen, d.h. 1,3-Oxazine mit einem Piperidinring als Spiro-Substituenten in 6-Stellung, leiten sich von 1-Oxa-3,9-diaza-spiro[5.5]undecan, einem neuen heterocyclischen Grundkörper, ab. Sie wurden alle mit Hilfe der folgenden dreistufigen Synthesefolge zugänglich gemacht: 1,3-dipolare Cycloadditionen von Nitriloxiden und Nitronen an Piperidinderivate mit einer exocylischen Methylengruppe gaben die entsprechenden spiro-substituierten Oxazolderivate3. Diese wurden anschließend hydrogenolytisch zu den -Aminoalkoholen4 gespalten, welche schließlich wieder unter Einschub von einem C-Atom zu den Zielstrukturen5–10 cyclisiert wurden: dadurch wurde einede facto-Ringerweiterung von Spiro-Oxazolen zu Spiro-Oxazinen erreicht.

     

First synthesis of a steroid containing an unstable 19-nor-androsta-1,5-dien-3-one system

Mechanisms involved in the maintenance of human pregnancy and initiation of labour are poorly defined. A novel steroid hormone named estradienolone (ED), and having an unusual 19-nor-androsta-1,5-dien-3-one system, was previously reported. However, ED is scarcely available from urine, placenta and blood of pregnant women. For this reason, we have synthesized ED in order to verify its proposed structure. Although a 1,5-dien-3-one system had already been described for a C19-steroid (androstane) nucleus (no possible aromatization), the synthesis of the 19-nor-analogue is a major challenge because this system is very sensitive to aromatization. We now describe the successful construction and characterization of this unstable system. Starting from nortestosterone, the synthesis of 17β-hydroxy-19-nor-androsta-1,5-dien-3-one (1) is based on a protection of the 5,6-double bond, the introduction of the second 1,2-double bond, the careful recovery of the exo double bond and a final regioselective oxidation or reduction.     

Synthesis of a Trisaccharide Related to the Cytotoxic Triterpenoid Saponins Isolated from the Bark of Albizia procera

Chemical synthesis of a trisaccharide related to the cytotoxic triterpenoid saponins isolated from the bark of Albizia procera has been accomplished through a concise stepwise glycosylation strategy starting from commercially available D ‐xylose, 2‐acetamido‐2‐deoxy‐D ‐glucose and L ‐arabinose. The target trisaccharide was designed with a 4‐methoxyphenyl (MP) aglycone to extend the scope of conversion to suitable glycoconjugates via selective removal of 4‐methoxyphenyl (MP) group. An unexpected phenomenon, i.e., the arabinosyl residue assumed the ¹C₄ conformation instead of the typical ⁴C₁ form, was observed. Deprotection could restore the normal conformation.     

Synthesis of Modified Poly(vinyl Alcohol)s and Their Degradation Using an Enzymatic Cascade

Poly(vinyl alcohol) (PVA) is a water-soluble synthetic vinyl polymer with remarkable physical properties including thermostability and viscosity. Its biodegradability, however, is low even though a large amount of PVA is released into the environment. Established physical-chemical degradation methods for PVA have several disadvantages such as high price, low efficiency, and secondary pollution. Biodegradation of PVA by microorganisms is slow and frequently involves pyrroloquinoline quinone (PQQ)-dependent enzymes, making it expensive due to the costly cofactor and hence unattractive for industrial applications. In this study, we present a modified PVA film with improved properties as well as a PQQ-independent novel enzymatic cascade for the degradation of modified and unmodified PVA. The cascade consists of four steps catalyzed by three enzymes with in situ cofactor recycling technology making this cascade suitable for industrial applications.     

Solid-Phase Synthesis of an Insect Pyrokinin Analog Incorporating an Imidazoline Ring as Isosteric Replacement of a trans Peptide Bond

A facile solid-phase synthetic method for incorporating the imidazoline ring motif, a surrogate for a trans peptide bond, into bioactive peptides is reported. The example described is the synthesis of an imidazoline peptidomimetic analog of an insect pyrokinin neuropeptide via a cyclization reaction of an iminium salt generated from the preceding amino acid and 2,4-diaminopropanoic acid (Dap).     

Quantitative Monitoring of Solid-Phase Synthesis Using Gated Decoupling 13C NMR Spectroscopy with a 13C-Enriched Protecting Group and an Internal Standard in the Synthesis of Sialyl LewisX Tetrasaccharide

Just tagging along. For the nondestructive quantitative monitoring of solid-phase oligosaccharide synthesis a ¹³C-enriched tag (*) was incorporated in the linker and a ¹³C-enriched protecting group (⧫) was included in the growing molecule. By integration of the signals in a gated decoupling ¹³C NMR experiment the reaction progress can be monitored. This method was demonstrated with the synthesis of sialyl Lewis^x tetrasaccharide on a Tentagel support ((P)). Bn=benzyl, PEG=poly(ethylene glycol).     

Reversible CO2 Addition to a Si=O Bond and Synthesis of a Persistent SiO2–CO2 Cycloadduct Stabilized by a Lewis Donor–Acceptor Ligand

The donor‐stabilized sila‐β‐lactone 1 reacts with CO₂ via a remarkable reversible [2+2]‐cycloaddition reaction to form the spiro‐cyclic silicon carbonate derivative 2 . Furthermore, photolysis of 2 under pressure of CO₂ affords the first persistent SiO₂–CO₂ cycloadduct 3 , presenting a Si₂O₄‐like structure, which is stabilized by a Lewis donor–acceptor type ligand. As predicted by theoretical calculations, in marked contrast to the thermodynamically stable SiO₂ dimer, the SiO₂–CO₂ mixed cycloadduct 3 is labile and readily releases CO₂.     

GC-MS/MS Determination of Steroid Hormones in Urine Using Solid-Phase Derivatization as an Alternative to Conventional Methods

Solid-phase analytical derivatization (SPAD) is a promising hybrid sample preparation technique combining the clean-up and preconcentration of the sample in a single step. In this work, a novel SPAD method based on the preparation of trimethylsilyl (TMS) derivatives of steroid hormones (testosterone, estrone, DHT, estriol, estradiol, and progesterone) in Phenomenex Strata C18-E (100 mg, 1 mL) cartridges has been developed and applied for their GC-MS/MS determination in human urine samples. The proposed procedure allows the detection and quantification of steroids with limits of 1.0–2.5 and 2.5–5 ng/mL, respectively. These characteristics are comparable with those obtained with a conventional liquid–liquid extraction, while the recovery of analytes in the proposed SPAD procedure is higher. The major advantages of SPAD are a short derivatization time, high efficiency, and the possibility to automatize the procedure. However, its cost-effectiveness in routine practice is still questionable.     

A direct conversion of carboxylic acids to methylthiomethyl esters using a microwave-assisted pummerer rearrangement with dimethylsulfoxide

A simple microwave-assisted method for the conversion of carboxylic acids to MTM esters is presented. This new process allows for rapid introduction of an MTM ester protecting group to a variety of carboxylic acids including alkyl, electron-rich aromatic, and long chain unsaturated carboxylic acids. The products isolated from this reaction are very pure after a simple extraction, which eliminates the need for further purification. The reaction has also been carried out on 1.50 g without deterioration of product yields or purity.     

Coupling of an advanced tri-functional building block by reductive amination leads to a protected backbone of a new archetype of foldamer

In order to advance our project to explore a new archetype of foldamer that preferentially folds in water, we designed two types of tri-functional building blocks with increasingly favorable ketone deprotection properties. Both were selected for their ease of synthetic access and the availability of bulk starting material. While the first building block proved unsuitable for efficient coupling by reductive amination, the second gave rise to almost quantitative yields according to mass spectral monitoring. It was thus effectively turned into a protected dimer and a tetramer. Although their subsequent purification prior to exhaustive ketone deprotection was preparatively impractical in view of their high polarity/water solubility, the stage is now set for transfer of the oligomer synthesis onto the solid phase on resin in view of the efficient five-step synthetic access from affordable bulk material, the favorable deprotection properties, the perspective for introduction of a variety of backbone substituents, and the possibility to protect the amine terminus by Boc or Fmoc protection.     

Solid-Phase Synthesis of Macrocyclic Systems by a Cyclorelease Strategy: Application of the Stille Coupling to a Synthesis of (S)-Zearalenone

No heteroatom required! In many solid-phase syntheses, after the release from the polymer support a heteroatom (e.g. O, S, N) remains in the substrate as a residue of a linking protecting group. With polymer-bound tin reagents cleavage and cyclization of the substrate with C–C bond formation (see picture) can now be achieved by intramolecular Stille coupling. S =substrate.     

Reductive deprotection of propargyl ether by a SmI2-amine-water system and its application to polymer-supported oligosaccharide synthesis

A SmI₂-amine-water system instantaneously deprotected aryl and alkyl propargyl ethers in a reductive manner. The utility of the propargyl group as a protecting group in oligosaccharide synthesis, and its application to polymer-supported oligosaccharide synthesis is described.     

Design,Synthesis, and Photovoltaic Characterization of a Small Molecular Acceptor with an Ultra‐Narrow Band Gap

The design of narrow band gap (NBG) donors or acceptors and their application in organic solar cells (OSCs) are of great importance in the conversion of solar photons to electrons. Limited by the inevitable energy loss from the optical band gap of the photovoltaic material to the open‐circuit voltage of the OSC device, the improvement of the power conversion efficiency (PCE) of NBG‐based OSCs faces great challenges. A novel acceptor–donor–acceptor structured non‐fullerene acceptor is reported with an ultra‐narrow band gap of 1.24 eV, which was achieved by an enhanced intramolecular charge transfer (ICT) effect. In the OSC device, despite a low energy loss of 0.509 eV, an impressive short‐circuit current density of 25.3 mA cm⁻² is still recorded, which is the highest value for all OSC devices. The high 10.9 % PCE of the NBG‐based OSC demonstrates that the design and application of ultra‐narrow materials have the potential to further improve the PCE of OSC devices.     

Synthesis and Catalytic Activity of Atrane-type Hard and Soft Lewis Superacids with a Silyl,Germyl, or Stannyl Cationic Center

The synthesis and isolation of atrane-type molecules 1 E⁺ (E=Si, Ge, or Sn) having a cationic group 14 elemental center are reported. The cations 1 E⁺ act as hard and soft Lewis superacids, which readily interact with various hard and soft Lewis basic substrates. The rigid atrane framework stabilizes the localized positive charge on the elemental center and assists the formation of the well-defined highly coordinated states of 1 E⁺. The cations were applied to the hydrodefluorination, Friedel-Crafts reaction, alkyne cyclization, and carbonyl reduction as Lewis acid catalysts. Most notably, [ 1 Si][ClO₄] exhibits unique chemoselectivity that depends on a solvent in the competitive reaction of silyl enol ether with a mixture of benzaldehyde dimethyl acetal and benzaldehyde. Our findings indicate the potential of hard and soft Lewis superacids in organic synthesis.