Tert-butoxycarbonyl Group Research Articles

In-situ Contamination Thickness Measurement by Novel Resist Evaluation System at NewSUBARU

To reduce the influence of carbon contamination growth, which is the origin of the resist outgassing during extreme ultraviolet (EUV) exposure, it is necessary to study the relationship between the outgassing species from the resist and carbon contamination growth during EUV exposure. Thus a novel evaluation system which enable the measurement of the carbon contamination thickness on a Mo/Si multilayer witness sample by in-situ ellipsometry in the resist outgassing environment under EUV exposure was installed at the beamline in the NewSUBARU synchrotron radiation facility. The carbon contamination thickness on the witness sample measured by in-situ ellipsometry is in good agreement with those measured using an atomic microscope and by reflectivity measurement. In addition, it is found that the time dependence of the carbon growth on a witness sample is due to the difference in outgassing species from the resist samples during EUV exposure. Furthermore, for the model resist of poly(hydroxystyrene) containing the protectiive group of tertial butoxycarbonyl group with a photoacid generator (PAG) and a quencher, the time dependence of contamination thickness was mainly due to the decomposition of outgassing species of the tert-butoxycarbonyl group and the residual casting solvent, such as propyleneglycol monomethyl ether acetate. In order to evaluate the carbon contamination thickness measurement, the in-situ measurement system was moved to the 10.8-m-long undulator beamline. The EUV light intensity flux was estimated to be the same level as that required in high-volume manufacturing.

Heterocyclic ketones in the pfitzinger reaction

By the reaction of isatin with heterocyclic ketones (N-tert-butoxycarbonyl derivatives of pyrrolidin-3-one, piperidin-4-one, piperidin-3-one, 1,2,3,4-tetrahydroquinolin-4-one, 8-azabicyclo[3.2.1]octan-3-one, tetrahydropyran-4-one, tetrahydrobenzopyran-4-one) in the presence of KOH (the Pfitzinger reaction) were synthesized quinoline-4-carboxylic acids [4,3]fused with the respective heterocycles. These acids were involved in the reactions with diazomethane and amines at the carboxy group leading to methyl esters and amides, respectively. The esters obtained reacted with hydrazine hydrate affording the acid hydrazides, which entered in the condensation with benzaldehyde to form phenylhydrazones. The esters and amides containing N-tert-butoxycarbonyl fragment lost the tert-butoxycarbonyl group easily to form the secondary amines dihydrochlorides, the [4,3]fused quinoline-4-carboxylic acid derivatives.

Discovery of novel (4-piperidinyl)-piperazines as potent and orally active acetyl-CoA carboxylase 1/2 non-selective inhibitors: F-Boc and triF-Boc groups are acid-stable bioisosteres for the Boc group

Novel (4-piperidinyl)-piperazine derivatives were synthesized and evaluated as ACC1/2 non-selective inhibitors. Optimization of the substituents on the nitrogen of the piperidine ring led to the identification of the fluorine substituted tert-butoxycarbonyl group. Advanced analog, 1,1,1-trifluoro-2-methylpropan-2-yl 4-{4-[(2-amino-6-methyl-1-benzothiophen-3-yl)carbonyl]piperazin-1-yl}piperidine-1-carboxylate (12c) showed potent inhibitory activities in enzyme-assay and cell-based assays. Compound 12c also exhibited reduction of hepatic de novo fatty acid synthesis in rats after oral administration.

Synthesis of Nonsymmetrical 5-Aryl-2-indolopyrrole Derivatives via Controlled Mono Suzuki-Miyaura Cross-Coupling on N-Boc-2,5-dibromopyrrole

The first example of mono Suzuki-Miyaura cross-coupling of N-Boc-2,5-dibromopyrrole with a boronic acid (indol-2-yl-boronic acid) is reported. The resulting 2-indolyl-5-bromopyrrole derivative was in turn coupled with a variety of aryl- or heteroaryl-boronic acids thereby providing the corresponding non-symmetrical 2,5-disubstituted pyrroles in good to excellent yields. The tert-butoxycarbonyl (Boc) groups could be easily removed to give the completely deprotected products.

Large-scale production of N, N′-diBoc-dityrosine and dityrosine by HRP-catalyzed N-Boc- l-tyrosine oxidation and one-step chromatographic purification

Dityrosine (DY) can be used as a biomarker to detect oxidative protein damage and selective proteolysis. It is generally prepared by horseradish peroxidase (HRP)-catalyzed oxidation of l-tyrosine (Y) followed by multistep chromatographic separations. In this study, we present an alternative method for the preparation of DY by HRP-catalyzed synthesis of N, N′-diBoc-dityrosine (DBDY) from N-Boc- l-tyrosine (BY). The presence of the tert-butoxycarbonyl (Boc) group ensured that the fraction of further oxidized by-products (e.g., trimers and pulcherosine) was quite low. The yield of DBDY (37.5%) was comparable to that reported for DY (> 26%). DBDY could be purified by a simple one-step silica column chromatography procedure that resulted in a purity of 89.7%. DBDY is considered to be better than DY for subsequent chemical reactions (for binding to polymers, amino acids, drugs, antibodies, etc.) because such reactions can be selectively performed by using the carboxylic acid and amine groups in the following sequence: first, the carboxylic acid groups are used; next, the Boc groups are removed; and finally, the amino groups are used. To prepare DY, the Boc groups in DBDY were simply and completely removed by treatment with trifluoroacetic acid.

Morita–Baylis–Hillman reaction of indole-2-carboxaldehyde: new vistas for indole-annulated systems

Abstract DABCO-mediated Morita–Baylis–Hillman reactions of several 1-substituted-indole-2-carboxaldehydes are disclosed. It was discovered that carboethoxy or tert-butoxycarbonyl groups installed at N-1 undergo cleavage under the reaction conditions to afford 2-substituted indoles. Utility of the N-substituted adducts for preparing a variety of annulated indoles has been exemplified.

Synthesis of N-Boc-Protected Bis(2-benzimidazolylmethyl)amines

Preparation of bis(1-tert-butoxycarbonyl-2-benzimidazolylmethyl)amines from N-tert-butoxycarbonyl-protected 2-chloromethylbenzimidazole is described. The reaction with primary amines containing several functional groups afforded bis(1-tert-­butoxycarbonyl-2-benzimidazolylmethyl)amines in good yields. Hydrogenolysis of bis(2-benzimidazolylmethyl)benzylamine, catalyzed by Pd(OH)2/C, cleaved the benzyl group, leaving the tert-­butoxycarbonyl and 2-benzimidazolylmethyl groups intact. The product of the latter reaction, bis(1-tert-butoxycarbonyl-2-benzimidazolylmethyl)amine, was thus obtained in 56% yield; the presence of the tert-butoxycarbonyl groups at the N-benzimidazole positions makes it amenable to further functionalization at the central nitrogen atom.

Concise Regiospecific Synthesis of 5-Chloropyrido[4,3-d]pyrimidin-4(3H)-one

A concise synthesis of 5-chloropyrido[4,3- D]pyrimidin-4(3 H)-onewas developed based on a unique regiospecific introduction of a TERT-butoxycarbonyl group at the C-3position of 4-amino-2-chloropyridine.

Reactions of N-substituted 3-azabicyclo[3.3.1]nonan-9-ones with N,N-, N,S-, and N,O-binucleophiles

Condensation of N-substituted 3-azabicyclo[3.3.1]nonan-9-ones with difunctional N,N-, N,S-, and N,O-centered nucleophiles (o-phenylenediamine, 1,2-diphenylethane-1,2-diamine, 2-aminobenzenethiol, cysteine, 2-aminophenol, serine) gave the corresponding spiro heterocyclic compounds fused at the C9 atom. Treatment of N-tert-butoxycarbonyl-substituted spiro compounds with anhydrous hydrogen chloride resulted in elimination of the tert-butoxycarbonyl group with formation of spiro[3-azabicyclo[3.3.1]nonane-9,2′-azole] hydrochlorides.

Reactions of 3-substituted 3-azabicyclo[3.3.1]nonan-9-ones with nitrogen-containing nucleophiles

Condensation of 3-substituted 3-azabicyclo[3.3.1]nonan-9-ones with hydroxylamine and hydrazine hydrate gave the corresponding oximes, hydrazones, and azines. Reductive amination of the title compounds in the presence of sodium triacetoxyhydridoborate led to the formation of 3-substituted 3-azabicyclo[3.3.1]nonan-9-amines which were converted into the corresponding dihydrochlorides by treatment with dry hydrogen chloride. Treatment of 3-tert-butoxycarbonyl derivatives with HCl under analogous conditions was accompanied by elimination of the tert-butoxycarbonyl group to produce 3-azabicyclo[3.3.1]nonan-9-amine dihydrochlorides.

Macrocyclic Hexaureas: Synthesis, Conformation, and Anion Binding

Five macrocylic compounds XXXXXX, XXDXXD, XDXDXD, XDDXDD, and DDDDDD with 48-membered rings, in which six xanthene and/or diphenyl ether fragments are linked through six urea (-NH-C(O)-NH-) groups, have been synthesized. In the cyclization step, a linear diamine was allowed to react with the appropriate diisocyanate by using a [5+1] (i.e., "XDXDX+D" for XDXDXD), [4+2] (DDDDDD), or [3+3] (XDDXDD) procedure. Compounds XXXXXX and XXDXXD were prepared from two molecules of the dimeric amine XX and two molecules of the respective monomeric diisocyanate (X or D) in a [2+1+2+1] (or 2x[2+1]) reaction. The (nonoptimized) yields in the cyclization step ranged from 45 to 80%. The linear precursor diamines or diisocyanates were obtained by analogous condensation reactions by using partial protection with a tert-butoxycarbonyl group. All the macrocyclic compounds and synthetic intermediates were characterized by (1)H NMR and mass spectra. Three different crystal structures were obtained for XDDXDD, which show the molecule in a more or less strongly folded conformation determined by intramolecular hydrogen bonding. The interaction of the hexaureas with selected anions was studied by (1)H NMR spectroscopy and UV absorption spectrophotometry.

Fabrication of Patterned Fluorescence Images in Electrospun Microfibers

Recently, generation of patterned fluorescence images based on the “precursor approach” has gained much attention. The concept of the ‘precursor approach’ is to use different electronic properties between the protected and unprotected forms. For example, a dye molecule is nonfluorescent when the key functional group of the dye molecule is protected with a protecting group. If the protecting group is removed under photoinduced chemical transformation, the fluorescence can be regenerated, allowing patterned fluorescent images in the polymer film by selective removal of the protecting group in the exposed areas. The “precursor approach” allows rapid and costeffective generation of patterned images in one step, without the need for additional wet developing processes. We have previously reported that the fluorescent quinizarin molecule can be readily converted to a nonfluorescent protected molecule t-BocQ by introduction of acid-labile tert-butoxycarbonyl (t-Boc) groups to the quinizarin hydroxyl moieties (Scheme 1). When the t-Boc groups were selectively removed by photogenerated acids, yellow fluorescent patterns were appeared in the UV exposed areas. Thus, the nonfluorescent t-BocQ precursor molecule was transformed to unprotected quinizarin by the photoinduced chemical transformation. The vast majorities of the fluorescence patterns generated based on the “precursor approach” have been fabricated in polymer film. During the course toward the development of fiber-based chemosensor systems, we have discovered a new strategy for the fabrication of patterned fluorescence images in microfibers. The key strategy and procedure employed for the fluorescence patterning is schematically presented in Figure 1. A viscous chloroform solution containing the precursor molecule t-BocQ (1.3 wt%), poly(methyl methacrylate) (PMMA) (19.6 wt%), and a photoacid generator (PAG), triphenylsulfonium triflate (0.6 wt%) is placed in a syringe. A high voltage (18 kV) is then applied to the metal syringe needle causing ejection of a charged polymer jet from the polymer solution. The microfibers are collected on the surface of a grounded aluminum plate (15 cm from the needle). A scanning electron microscope (SEM) image confirms the formation of microfibers (Figure 1). Photomasked UV irradiation of the electrospun fiber should generate strong acids from the PAG in the exposed areas. The photochemically produced strong acids should promote catalytic deprotection of the t-Boc groups from the precursor molecules, allowing patterned fluorescence images in the polymer fibers. In order to investigate the feasibility of fluorescence patterning, the polymer fiber mats obtained as described above were irradiated with 254 nm UV light through a photomask for 2 min. The UV-treated fiber mats were then placed on a hot plate (100 C) for 1 min for a post-exposure

Synthesis of N, N-Ac,Boc laurylthio sialoside and its application to O-sialylation

The combination of the 5- N- tert-butoxycarbonyl (Boc) group of laurylthio sialoside and cyclopentyl methyl ether (CPME) as a solvent enhanced the reactivity and α-selectivity of the sialyl donor during sialylation. Selective deprotection of the N-Boc group of sialoside, including an acid-sensitive isopropylidene function, was successfully achieved by Yb(OTf) 3–SiO 2. Transformation of N, N-Ac,Boc into an N-acetylglycolyl group of sialoglycoside was easily performed via selective N-deacylation of the mixed Ac- N-Boc carbamate, subsequent Boc group removal, and acylation.

Colorimetric Anion Sensing and Color Imaging Based on Catalyzed Deprotection in a New Azonaphthol Chromophore

We synthesized an ortho-phenylazonaphthol compound of which hydroxyl group was protected by a thermo-labile tert-butoxycarbonyl (t-Boc) group, in which hydroxyazo- and hydrazone-tautomerism could be blocked. The chromophore obtained by protection with t-Boc group was exclusively present as a hydroxyazo tautomer and exhibited blue-shifted absorption spectrum compared to their parent azohydrazone tautomerizing chromophore. With this compound, we performed colorimetric anion sensing based on the deprotection-induced possible azohydrazone formation in dye chromophore subsequently resulting in naked-eye color change. Besides, the t-Boc protected chromophore could be used as a color imaging material via thermolysis of thermo-labile t-Boc groups resulting in formation of azohydrazone form with red shifted absorption.

High‐Resolution Patterning of Molecular Glasses Using Supercritical Carbon Dioxide

A glass-forming molecule, consisting of hexa(hydroxyphenyl)benzene [HHPB] protected with six tert-butoxycarbonyl (t-Boc) groups, is patterned and developed to produce features as small as 50 nm (see Figure) using supercritical CO2 (scCO2). Protected HHPB was shown to be completely soluble in scCO2 without incorporation of either fluorine or silicon but could be rendered insoluble in scCO2 by acid-catalyzed removal of the solubilizing t-Boc groups.

Synthesis of chiral 1,2-diamine immobilized on polystyrene and its application to asymmetric hydrogenation of aromatic ketones

A novel chiral 1,2-diamine monomer ( S,S)- 12 has been synthesized and copolymerized with styrene to give cross-linked polymer. After deprotection of the tert-butoxycarbonyl groups, polymer-supported chiral 1,2-diamine ( S,S)- P was obtained. The primary 1,2-diamine moieties on the polymer have been allowed to form the complex with RuCl 2/( S)-BINAP. The polymeric chiral complex was used as a catalyst of asymmetric hydrogenation of aromatic ketones to yield the corresponding secondary alcohols in quantitative conversion with high level of enantioselectivity. The polymeric catalyst was recycled several times without any loss of the catalytic activity.

Toward the Next-Generation Drug Delivery Vehicle: Synthesis of a Dendrimer with Four Orthogonally Reactive Groups

The synthesis of a dendrimer based on melamine that displays multiple copies of four orthogonally reactive groups, three on the surface and one on the interior, is described. The three groups on the surface are nucleophilic and include four free hydroxyl groups, four hydroxyl groups masked as tert-butyldiphenylsilyl (TBDPS) ethers, and 16 amines masked as tert-butoxycarbonyl (BOC) groups. The core of the dendrimer displays two electrophilic monochlorotriazines. The dendrimer is available in seven linear steps (eight total steps) at 55% overall yield for the longest linear sequence.

Efficient and selective cleavage of the tert-butoxycarbonyl (Boc) group under basic condition

A simple, efficient and mild method for the selective cleavage of tert-butoxycarbonyl (Boc) from dicarbamates and a carbonyl or aromatic ring in conjugation with the nitrogen atom bearing the Boc-group is described under basic condition.

Amphiphilic Polymethacrylate Derivatives as Antimicrobial Agents

We have investigated the structure-activity relationship of cationic amphiphilic polymethacrylate derivatives in antimicrobial and hemolytic assays. The polymers were prepared by radical copolymerizations of N-(tert-butoxycarbonyl)aminoethyl methacrylate and butyl methacrylate in the presence of methyl 3-mercaptopropionate as a chain transfer agent to give precursor polymers protected with a tert-butoxycarbonyl (Boc) group. Subsequent treatment of the Boc-protected polymers with TFA affords the desired cationic random copolymers. We examined antimicrobial and hemolytic activities of a series of polymers having a wide range of mole percentage of butyl groups (0-60%) in three different molecular weight (MW) ranges. The smallest polymers (MW < 2000) showed the lowest MIC and reduced hemolytic activity compared to that of the higher MW ones. In addition, polymers containing a high percentage of butyl groups are less selective for bacterial cells than their less hydrophobic counterparts.

Synthesis and Properties of Tailor-Made Supramolecular Photo Acid Generators for Conducting Patterns of Polyaniline

We investigated newly designed photo acid generators (PAGs) based on a layer-controlled supramolecular polymer N-substituted with camphor or toluenesulfonyloxy units to achieve better conductivity of polyaniline array patterns via microstructure control. Synthesis and properties of these PAGs containing sulfonyloxymaleimide/furan terephthalic acid derivatives (SOMI/F TA) were described. The synthesized PAGs produced photochemically and thermally corresponding sulfonic acids that could catalyze deprotection of the acid-labile tert-butoxycarbonyl (t-BOC) groups in the polyaniline−t-BOC chains and dope emeraldine bases into corresponding conductive salts as well. Thus, the resultant PANi(t-BOC) was a so-called “negative photoresist” capable of generating high-resolution conducting arrays in which 1-μm wide lines and spaces have been delineated in 0.6-μm film. The combination of this simple method for the generation of conducting patterns using tailor-made PAGs and the fact that PANi(t-BOC) completely returns...