Trityl Ethers Research Articles

Discovery of dehydroandrographolide derivatives with C19 hindered ether as potent anti-ZIKV agents with inhibitory activities to MTase of ZIKV NS5

Infection by Zika virus (ZIKV), a mosquito-transmitted arbovirus and a member of Flavivirus, could make pediatric microcephaly and Guillain–Barré syndrome, which remains an ongoing global threat. The efficient antivirals to ZIKV infection are of great medical need. Andrographolide and its analogues were discovered to be active against flaviviral infection. In this study, we discovered some dehydroandrographolide derivatives of 3-oximido- or 3-alcohol-19-hindered ether to be potent anti-ZIKV agents with low cytotoxicities (CC50 > 200 μM). Time of addition assay suggests that compound 5a and its analogues act on inhibition of post-entry stage of ZIKV life cycle. It is discovered by experimental and molecular docking studies that active anti-ZIKV compounds of 3a, 5a, 5b and 5c possess inhibitory activities of ZIKV NS5 MTase (methyl transferase) enzymatic activity. Preliminary SAR reveals that C19-modification with bulky groups is necessary for anti-ZIKV infection and replication, anti-ZIKV activity of 5a comes from itself bearing hindered trityl ether but not from its instability, the backbone of dehydroandrographolide is more effective against ZIKV infection than that of andrographolide, and 3-oxime derivatives are more active against ZIKV infection than 3-alcohol derivatives. To our knowledge, 5a is the first reported MTase inhibitor of andrographolide derivatives. More importantly, discovery of active compound 5b with acid-stable 19-OCHPh2 against ZIKV infection is valued and gives us a clue to design and discover generally acid-stable anti-ZIKV agents.

Synthesis of amphiphilic poly(ethylene glycol)-block-poly(methyl methacrylate) containing trityl ether acid cleavable junction group and its self-assembly into ordered nanoporous thin films

Abstract A strategy for the synthesis of well defined poly(ethylene glycol)-block-poly(methyl methacrylate) diblock copolymers containing trityl ether acid cleavable junctions is demonstrated. This approach is achieved by using a combination of poly(ethylene glycol) macroinitiator containing a trityl ether end group, which is susceptible to acid cleavage, and atom transfer radical polymerization technique. The trityl ether linkage between blocks can be readily cleaved in solution or in solid phase under very mild acid condition, which has been confirmed by 1H NMR. These diblock copolymers have been used to successfully fabricate nanoporous thin films by acid cleavage of trityl ether junction followed by complete removal of poly(ethylene glycol) block. The fabricated nanoporous thin films may have a wide range of application such as Recessed Nanodisk-array electrode (RNE) or as a template to fabricate nanoelectrode array for senor applications.

ChemInform Abstract: LiCl‐Mediated, Easy, and Low‐Cost Removal of the Trityl Group from Protected Alcohols and Diols.

Abstract The reaction of primary, secondary, phenyl, allyl, and benzyl trityl ethers with lithium chloride in methanol at reflux led to deprotection of the trityl group affording the corresponding alcohol in good to excellent yields under mild reaction conditions.

Indium-mediated cleavage of the trityl group from protected alcohols and diols

The reaction of primary, secondary, allylic and benzylic trityl ethers with indium powder in MeOH/NH4Cl led to reductive cleavage of the trityl-oxygen bond, affording the corresponding alcohols in good to excellent yield under very mild reaction conditions. The detritylation process could successfully be extended to mono and detritylated diols. This methodology represents a new and efficient detritylation procedure under mild reaction conditions.

LiCl-mediated, easy, and low-cost removal of the trityl group from protected alcohols and diols

The reaction of primary, secondary, phenyl, allyl, and benzyl trityl ethers with lithium chloride in methanol at reflux led to deprotection of the trityl group affording the corresponding alcohol in good to excellent yields under mild reaction conditions.

Syntheses and complexing ability of α-d-gluco- and α-d-xylofuranoside-based lariat ethers

Chiral monoaza-15-crown-5 lariat ethers attached to a 1,2-O-isopropylidene-α-d-glucofuranoside unit (10–13), monoaza-16-crown-5 lariat ethers fused to 1,2-O-isopropylidene-α-d-glucofuranoside- (18) and to 1,2-O-isopropylidene-α-d-xylofuranoside units (23 and 24) have been synthesized. The alkali metal- and ammonium picrate extracting ability of these macrocycles was investigated in dichloromethane–water system. In general, the 15-membered macrocycles (10–13) showed, for almost all cations, a more considerable extracting ability, than the 16-membered lariat ethers (18, 23 and 24). Plasticized PVC membrane electrodes (ISEs) were prepared from the α-d-glucofuranoside-based triphenylmetyl (trityl) ether derivative (18), and its potentiometric selectivities and complex formation constants were determined with the segmented sandwich membrane method. Furthermore, the binding affinities of ionophores to different metal ions were also measured by competitive ESI–MS experiments. One of the 1,2-O-isopropylidene-α-d-glucofuranoside-based lariat ethers (13) exhibited a high selectivity for silver ion (Ag+).

Nickel‐Catalyzed Reductive Addition of Aryl/Benzyl Halides and Pseudohalides to Carbodiimides for the Synthesis of Amides

AbstractA Nickel‐catalyzed reductive process is described for the direct amidation of benzyl and aryl halides using carbodiimides as the amidating agent. Moreover, aryl and benzyl C–O electrophiles such as triflate, acetate, tosylate, trityl ether, and pivalate were converted into amides using this method. The in‐situ‐generated Ni0 acts as a catalyst for the reaction at room temperature for benzylic substrates, and 70 °C for aryl electrophiles. This new nickel‐catalyzed reductive coupling protocol provides a general and operationally simple method for the synthesis of diverse amides using carbodiimides. Amides bearing bulky substituents can be synthesized by this strategy in high yield, which demonstrates its effectiveness in amide synthesis.

Gold(I)‐Catalyzed Synthesis of Unsymmetrical Ethers Using Alcohols as Alkylating Reagents

AbstractA microwave‐irradiated alcohol‐protecting strategy based on gold catalysis utilizing benzyl alcohol, tert‐butyl alcohol and triphenylmethanol as alkylating reagents has been developed. This protecting strategy has wide functional group tolerance with satisfactory yields for the majority of the selected alcohols. The mechanism of this transformation was probed with oxygen‐18 isotope labelled alcohols assisted by GC‐MS techniques and chemical kinetic experiments. This strategy provides an efficient, straightforward and alternative approach to the preparation of benzyl, tert‐butyl and trityl ethers in organic synthesis.magnified image

ChemInform Abstract: An Efficient and Environmentally Friendly Method for Directly Converting Trityl and Benzyl Ethers to the Corresponding Acetates.

AbstractA simple one‐pot procedure using HClO4 on silica as heterogeneous reusable catalyst allows the selective conversion of primary benzyl and trityl ethers into acetates.

Highly efficient protection of alcohols as trityl ethers under solvent-free conditions, and recovery catalyzed by reusable nanoporous MCM-41-SO3H

An efficient method was developed for the protection of alcohols as trityl ethers using triphenylmethanol in the presence of nanoporous MCM-41-SO3H as a heterogeneous catalyst under solvent-free ball-milling at room temperature. Low catalyst loading, high efficiency, reusability are among the advantages of this new solvent-free and environmentally friendly method. The deprotection of the produced trityl ethers was also efficiently achieved using the same catalyst in wet acetonitrile.

An Efficient and Environmentally Friendly Method for Directly Converting Trityl and Benzyl Ethers to the Corresponding Acetates

AbstractAcid sensitive benzyl and trityl ethers are frequently used as protecting groups to mask alcohols. They are also needed to be transformed into more stable ester groups toward acids in multistep synthesis. A mild and efficient one‐pot protocol for the selective transformation of benzyl and trityl ethers into their corresponding acetates was successfully developed. Several distinct advantages to this procedure include direct transformation, minimal generation of waste, a non‐aqueous workup and the recovery and recycling of the benzyl acetate and trityl alcohol by‐products, which were readily recovered in greater than 90% yields.

Acid‐catalysed hydrolysis of trityl derivatives in strongly acidic aqueous media

The kinetics of hydrolysis (deamination or dealcoholation) of tritylamines and 2,2,2‐trifluoroethyl ethers and their corresponding 4‐methoxy, 4,4′‐dimethoxy‐, and 4,4′,4″‐trimethoxy‐substituted analogues in aqueous solutions up to 3.5 mol · dm−3 in strong acid have been investigated at constant ionic strength. In all cases, acid‐catalysed hydrolytic processes have been observed, with finite reactivity at [H3O+] = 0. Strong upward curvature has been observed for kobs versus [HClO4]. Analysis of this dependence in terms of the HR acidity function and the X0 excess acidity scale allow explanation of the observed behaviour in terms of the increasing differences between concentrations and activities of the various species involved in the processes, including water, for which the activity coefficient strongly diverges from its standard state value as the acidity increases. This analysis has shown that, by taking account of the effect of the ionic strength, the same mechanistic models proposed for mildly acidic solutions are valid in more highly concentrated acid media. These comprise (i) protonation of the trityl ether followed by C–O bond heterolysis to give a carbenium ion–alcohol (ion–molecule) pair which can separate, and (ii) C–N bond heterolysis of the protonated tritylamine to give a carbenium ion–amine (ion–molecule) pair followed by separation of the fragments or protonation of the amine and subsequent separation of the ions. Each separated (substituted) trityl carbenium ion, regardless of its provenance, is invariably captured by a solvent molecule (water). Copyright © 2013 John Wiley & Sons, Ltd.

Hydration of Terminal Alkynes Catalyzed by Water-Soluble Cobalt Porphyrin Complexes

Water-soluble cobalt(III) porphyrin complexes were found to promote the hydration of terminal alkynes to give methyl ketones. The alkyne hydration proceeded in good to excellent yield with 0.1 to 2 mol % cobalt catalyst 1 and was compatible with the presence of acid/base- or redox-sensitive functional groups such as alkyl silyl ethers; allyl ethers; trityl ethers; benzyl ethers; carboxylic esters; boronic esters; carboxamides; nitriles; and nitro, iodo, and acetal groups. Some of the alkyne substrates tested here are otherwise difficult to hydrate. The alkyne hydration can be performed on a gram scale, and the catalyst can be recovered by aqueous workup.

Elaboration of the ether cleaving ability and selectivity of the classical Pearlman's catalyst [Pd(OH)2/C]: concise synthesis of a precursor for a myo-inositol pyrophosphate

The cleavage of propargyl, allyl, benzyl, and PMB ethers by Pd(OH)2/C can be tuned in that order, by varying the reaction conditions. Other moieties such as C–C double bonds, esters, trityl ether, p-bromo and p-nitrobenzyl ethers are stable to these reaction conditions. Cleavage of allyl ethers can be made catalytic by using 1:1 mixture of Pd(OH)2/C and Pd/C. The synthetic potential of the selective ether cleaving ability of Pd(OH)2/C, essentially under neutral conditions, has been demonstrated by an efficient synthesis of a precursor for the preparation of an inositol pyrophosphate derivative.

Reaction of several resveratrol glycoside derivatives with hypochlorites in various media

The reactions of pterostilbenoside (trans-3,5-dimethoxystilben-4′-O-β-D-glucoside) and Ar–O–Tr derivatives of resveratroloside (3,5-dihydroxystilben-4′-O-β-D-glucoside) and pinostilbenoside (3-methoxy-5-hydroxystilben-4′-O-β-D-glucoside) with NaOCl and t-BuOCl in the presence of the stable nitroxyl radical TEMPO were studied in various media. It was found that the principal product of pterostilbenoside transformation was its 2,6-dichloroderivative, a part of which was oxidized to form 2,6-dichloropterostilbene glucuronide. Trityl ethers of resveratroloside and pinostilbenoside reacted with the hypochlorites to form mixtures of products.

ChemInform Abstract: A New Stereospecific Method for 1,2-cis-Glycosylation.

Abstract A new stereospecific method for 1,2- cis -glycosylation involves the reaction of 1,2- trans -glycosyl thiocyanates with sugar trityl ethers in the presence of triphenylmethylium perchlorate. The method has been applied to give disaccharide derivatives with (1→6), (1→4), (1→3), and (1→2) linkages.

High Surface Area Poly(3-hexylthiophenes) Thin Films from Cleavable Graft Copolymers

A strategy for the fabrication of high surface area poly(3-hexylthiophene) thin films by removal of nanoscale domains formed from graft copolymers is presented. This approach relies on the synthesis and characterization of cleavable graft copolymers based on regioregular poly(3-hexylthiophene) (rr-P3HT) main chain and sacrificial poly(styrene) side chains. An alkoxyamine initiator based on 2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO) was incorporated at the 3-position of the functionalized thienyl repeat unit, 2, via a cleavable trityl ether linker. Grignard metathesis (GRIM) copolymerization of 2 and 2,5-dibromo-3-hexylthiophene afforded regioregular P3HT with randomly incorporated alkoxyamine groups. Polymerization of styrene from the P3HT backbone for different time periods afforded graft copolymers with controllable sacrificial chain lengths. These materials were characterized using an array of techniques such as 1H and 13C NMR spectroscopy and size exclusion chromatography (SEC). An approach to obtain nanoporous P3HT thin films by cleavage of the trityl ether linker followed by complete removal of poly(styrene) is reported with the as-cast graft copolymer thin films displaying an irregular microphase-separated structure with an average domain size ∼30 nm as determined by grazing incidence small-angle X-ray scattering (GISAXS) measurements. Significantly, this length scale was conserved after removal of the sacrificial component which allows this strategy to have potential application in diverse fields such as organic photovoltaics.

FeCl3-Catalyzed Tritylation of Alcohols in Ionic Liquids

A simple and efficient protection of alcohols as trityl ethers is described using trityl chloride in the presence of 5 mol% FeCl3 as catalyst in ionic liquids at room temperature in shorter reaction times. This mild and efficient method gives access to the protection of a wide range of alcohols in good yields. The use of ionic liquid allows easy separation of the product and recycling of catalyst.

Trityl Ethers: Molecular Bevel Gears Reporting Chirality through Circular Dichroism Spectra

Mehr als nur eine Schutzgruppe: Die Tritylgruppe wird in Tritylethern von der Chiralität eines Alkylsubstituenten beeinflusst, wie aus den CD-Spektren solcher tritylgeschützten chiralen Alkohole hervorgeht. Das Trityl-CD-Verfahren gibt Einblicke in die Struktur und Funktion chiraler molekularer Getriebe und belegt den Zusammenhang zwischen der Absolutkonfiguration von Molekülen und dem Muster ihres Cotton-Effekts.

Trityl Ethers: Molecular Bevel Gears Reporting Chirality through Circular Dichroism Spectra

Trityl Ethers: Molecular Bevel Gears Reporting Chirality through Circular Dichroism Spectra