Photosensitive polybenzoxazole based on a poly(o‐hydroxy amide), a dissolution inhibitor,and a photoacid generator

A positive‐type photosensitive polybenzoxazole (PSPBO), based on a poly(o‐hydroxy amide) (PHA), the dissolution inhibitor (DI) 9,9‐bis(4‐tert‐butoxycarbonyloxyphenyl)fluorene (t‐Boc BHF), and the photoacid generator (5‐propylsulfonyloxyimino‐5H‐thiophene‐2‐ylidene)‐(2‐methylphenyl)acetonitrile (PTMA), was developed. Several new tert‐butoxycarbonylated compounds as DIs for PSPBOs were prepared from phenolic compounds having a cardolike structure with di‐tert‐butyl dicarbonate in the presence of 4‐dimethylaminopyridine. Among them, t‐Boc BHF and 5,5′,6,6′‐tetra(tert‐butoxycarbonyl)‐3,3,3′,3′‐tetramethyl‐1,1′‐spirobiindane acted as excellent DIs, giving a large dissolution contrast between the exposed and unexposed areas in a 2.38 wt % tetramethylammonium hydroxide solution (TMAHaq)/5 wt % iso‐propanol (i‐PrOH). The dissolution behavior of this PSPBO system was studied in relation to the PTMA and t‐Boc BHF loadings and postexposure baking temperature. A PSPBO consisting of PHA (77 wt %), t‐Boc BHF (20 wt %), and PTMA (3 wt %) exhibited a sensitivity of 34 mJ/cm² and a contrast of 5.8 when exposed to 365‐nm light (i‐line) and developed with an aqueous alkaline developer, 2.38 wt % TMAHaq/5 wt % i‐PrOH. A clear, positive image with 6‐μm features and a 10‐μm‐thick pattern with high sensitivity and contrast was produced by contact printing and converted into polybenzoxazole patterns upon heating at 350 °C for 1 h. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 661–668, 2007     

Biosynthesis of Streptolidine Involved Two Unexpected Intermediates Produced by a Dihydroxylase and a Cyclase through Unusual Mechanisms

Streptothricin‐F (STT‐F), one of the early‐discovered antibiotics, consists of three components, a β‐lysine homopolymer, an aminosugar D ‐gulosamine, and an unusual bicyclic streptolidine. The biosynthesis of streptolidine is a long‐lasting but unresolved puzzle. Herein, a combination of genetic/biochemical/structural approaches was used to unravel this problem. The STT gene cluster was first sequenced from a Streptomyces variant BCRC 12163, wherein two gene products OrfP and OrfR were characterized in vitro to be a dihydroxylase and a cyclase, respectively. Thirteen high‐resolution crystal structures for both enzymes in different reaction intermediate states were snapshotted to help elucidate their catalytic mechanisms. OrfP catalyzes an Fe^II‐dependent double hydroxylation reaction converting L ‐Arg into (3R,4R)‐(OH)₂‐L ‐Arg via (3S)‐OH‐L ‐Arg, while OrfR catalyzes an unusual PLP‐dependent elimination/addition reaction cyclizing (3R,4R)‐(OH)₂‐L ‐Arg to the six‐membered (4R)‐OH‐capreomycidine. The biosynthetic mystery finally comes to light as the latter product was incorporation into STT‐F by a feeding experiment.     

Synthetic Studies on Kinamycin Antibiotics: Synthesis of a Trioxygenated Benz[f]indenone and its Diels–Alder Reaction to a Kinamycin Skeleton

A benzo[b]fluorene skeleton such as 10 , a basic four‐ring system in the revised diazo structures 3 of kinamycin antibiotics, was synthesized by Diels‐Alder reaction between dienophile 4,7,8‐trioxygenated 1H‐benz[f]inden‐1‐one 11 and Danishefsky‐type diene 7 . The indenone 11 was prepared by deoxygenation of 2,3‐dihydro‐1H‐benz[f]inden‐1‐one 12 with the inexpensive 1‐hydroxy‐1,2‐benziodoxol‐3(1H)‐one 1‐oxide (IBX) after modification of the known protocol. Indenone 12 in turn was obtained from naphthalene‐1,5‐diol ( 14 ) via an intramolecular Friedel‐Crafts cyclization of naphthalene‐2‐propanoic acid 13 as a key step.     

Morphological change of a diblock copolymer film induced by selective doping of a photoactive chromophore

Tetrakis‐5,10,15,20‐(4‐carboxyphenyl)porphyrine (TCPP) was position‐selectively introduced into a diblock copolymer film of polystyrene‐block‐poly(4‐vinylpyridine) (PS‐b‐P4VP) with a sea–island microphase structure. By immersing the PS‐b‐P4VP film into a solution of TCPP/methanol, TCPP was introduced into the island parts comprising P4VP phase. The morphology of the island parts depended on the immersion time and TCPP concentration. A schematic model for the morphological change caused by the phase‐selective introduction of TCPP was proposed. © 2006 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 45: 368–375, 2007     

Anionic ring‐opening polymerization of a five‐membered cyclic carbonate having a glucopyranoside structure

Anionic ring‐opening polymerizations of methyl 4,6‐O‐benzylidene‐2,3‐O‐carbonyl‐α‐D ‐glucopyranoside (MBCG) were investigated using various anionic polymerization initiators. Polymerizations of the cyclic carbonate readily proceeded by using highly active initiators such as n‐butyllithium, lithium tert‐butoxide, sodium tert‐butoxide, potassium tert‐butoxide, and 1,8‐diazabicyclo[5.4.0]undec‐7‐ene, whereas it did not proceed by using N,N‐dimethyl‐4‐aminopyridine and pyridine as initiators. In a polymerization of MBCG (1.0 M), 99% of MBCG was converted within 30 s to give the corresponding polymer with number‐averaged molecular weight (M_n) of 16,000. However, the M_n of the polymer decreased to 7500 when the polymerization time was prolonged to 24 h. It is because a backbiting reaction might occur under the polymerization conditions. © 2013 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2013     

Toward the Total Synthesis of Onchidin,a Cytotoxic Cyclic Depsipeptide from a Mollusc

The total synthesis of onchidin ( 1 ), a cytotoxic, C₂‐symmetric cyclic decadepsipeptide from a marine mollusc, according to the published structure, is described. A novel β‐amino acid, (2S,3S)‐3‐amino‐2‐methyl‐7‐octynoic acid (AMO), was efficiently prepared in high yield with high diastereo‐ and enantioselectivity based on a catalytic asymmetric three‐component Mannich‐type reaction with a chiral zirconium catalyst. The formation of sterically unfavorable N‐methyl amide and hindered ester bonds were successfully demonstrated, and final macrocyclization was achieved at a secondary‐amide site. Completion of the synthesis of 1 suggested that a revision of the structure of the natural product is required. Two diastereomers were also synthesized as candidates for the actual structure of onchidin. Furthermore, efficient solid‐phase methods were employed for the combinatorial synthesis of other derivatives to clarify the real structure of onchidin. The solid‐phase assembly of a pentadepsipeptide containing all the building blocks was established followed by dimeric cyclization in solution.     

Helicity Induction and Memory of the Macromolecular Helicity in a Polyacetylene Bearing a Biphenyl Pendant

A novel, cis‐transoidal poly‐(phenylacetylene) bearing a carboxybiphenyl group as the pendant (poly‐ 1 ) was prepared by polymerization of (4′‐ethoxycarbonyl‐4‐biphenylyl)acetylene with a rhodium catalyst followed by hydrolysis of the ester groups. Upon complexation with various chiral amines and amino alcohols in dimethyl sulfoxide (DMSO), the polymer exhibited characteristic induced circular dichroism (ICD) in the UV/Vis region due to the predominantly one‐handed helix formation of the polymer backbone as well as an excess of a single‐handed, axially twisted conformation of the pendant biphenyl group. Poly‐ 1 complexed with (R)‐2‐amino‐1‐propanol showed unique time‐dependent inversion of the macromolecular helicity. Furthermore, the preferred‐handed helical conformation of poly‐ 1 induced by a chiral amine was further “memorized” after the chiral amine was replaced with achiral 2‐aminoethanol or n‐butylamine in DMSO. In sharp contrast to the previously reported memory in poly((4‐carboxyphenyl)acetylene), the present helicity memory of poly‐ 1 was accompanied by memory of the twisted biphenyl chirality in the pendants. Unprecedentedly, the helicity memory of poly‐ 1 with achiral 2‐aminoethanol was found to occur simultaneously with inversion of the axial chirality of the biphenyl groups followed by memory of the inverted biphenyl chirality, thus showing a significant change in the CD spectral pattern.     

Photocontrol of the Catalytic Activity of a β‐Cyclodextrin Bearing Azobenzene and Histidine Moieties as a Pendant Group

An azobenzene group was linked to β‐cyclodextrin via a histidine spacer ( 1 ) to produce a photoresponsive catalyst. The ester hydrolysis of p‐nitrophenyl acetate, Boc‐L ‐alanine‐p‐nitrophenyl ester and Boc‐D ‐alanine‐p‐nitrophenyl ester was examined in the presence of trans‐ 1 or cis‐ 1 . In the case of cis‐ 1 , the cyclodextrin cavity was used as the substrate binding site during imidazole‐catalyzed ester hydrolysis. This was not possible in the case of trans‐ 1 due to the inclusion of the trans‐azobenzene moiety in the cyclodextrin cavity. Consequently, the catalytic mechanism switches in an on‐off fashion on UV irradiation, associated with the conversion of the azobenzene moiety of 1 from trans to cis.     

Synthesis of a Novel ABC Triblock Copolymer with a Rigid‐Rod Block via Atom Transfer Radical Polymerization

Summary: A novel ABC triblock copolymer with a rigid‐rod block was synthesized by atom transfer radical polymerization (ATRP). First, a poly(ethylene oxide) (PEO)‐Br macroinitiator was synthesized by esterification of PEO with 2‐bromoisobutyryl bromide, which was subsequently used in the preparation of a poly(ethylene oxide)‐block‐poly(methyl methacrylate) (PEO‐b‐PMMA) diblock copolymer by ATRP. A poly(ethylene oxide)‐block‐poly(methyl methacrylate)‐block‐poly{2,5‐bis[(4‐methoxyphenyl)oxycarbonyl]styrene} (PEO‐b‐PMMA‐b‐PMPCS) triblock copolymer was then synthesized by ATRP using PEO‐b‐PMMA as a macroinitiator.

ABC triblock copolymer with a rigid‐rod block.     

Porphyrin Analogues of a Trityl Cation and Anion

Porphyrin‐stabilized meso‐ or β‐carbocations were generated upon treatment of the corresponding bis(4‐tert‐butylphenyl)porphyrinylcarbinols with trifluoroacetic acid (TFA). Bis(4‐tert‐butylphenyl)porphyrinylcarbinols were treated with TFA to generate the corresponding carbocations stabilized by a meso‐ or β‐porphyrinyl group. The meso‐porphyrinylmethyl carbocation displayed more effective charge delocalization with decreasing aromaticity compared with the β‐porphyrinylmethyl carbocation. A propeller‐like porphyrin trimer, tris(β‐porphyrinyl)carbinol, was also synthesized and converted to the corresponding cation that displayed a more intensified absorption reaching over the NIR region. meso‐Porphyrinylmethyl carbanion was generated as a stable species upon deprotonation of bis(4‐tert‐butylphenyl)(meso‐porphyrinyl)methane with potassium bis(trimethylsilyl)amide (KHMDS) and [18]crown‐6, whereas β‐porphyrinylmethyl anions were highly unstable.     

Paranolin: a New Xanthene‐Based Metabolite from Paraphaeosphaeria nolinae

A new xanthene‐based, polycyclic metabolite, paranolin (= (2R,3aS,12aR)‐3,3a‐dihydro‐3a‐hydroxy‐8‐(hydroxymethyl)‐2‐(1‐hydroxy‐1‐methylethyl)‐9‐methoxy‐10‐methylfuro[3,2‐d]xanthen‐6(2H)‐one; 1 ) was isolated from a culture of Paraphaeosphaeria nolinae (IFB‐E011), an endophytic fungus residing in the normal stem of the artemisinin‐producing plant Artemisia annua (Asteraceae). The structure of 1 was elucidated by extensive spectroscopic analyses. Although not substantially active against the human colon (SW1116) and human cervical carcinoma (Hela) cell lines, this metabolite seems to be the first example of a xanthene‐derived secondary metabolite. Its possible biosynthetic origin (Scheme) and its significance as a phyllogenetic marker are discussed in brief.     

Syntheses of Prekinamycin and a Tetracyclic Quinone from Common Synthetic Intermediates

Towards total synthesis of a series of kinamycin and related antibiotics via common synthetic intermediates, total synthesis of prekinamycin was achieved via Suzuki coupling of naphthaleneboronic acid and bromobenzene derivative, intramolecular Friedel? Crafts reaction of 2‐(naphthalen‐2‐yl)benzoic acid, and diazotization in ten steps from 3,5‐dimethylphenol. Synthetic studies towards kinamycin antibiotics was also examined, and the tetracyclic quinone core for kinamycins was synthesized. Palladium‐catalyzed site‐selective hydroxylation of a benzoic acid derivative with the AB‐D ring part was successfully applied to the selective D‐ring functionalizations.     

Synthesis of Substituted Pyrrolo[3,4‐a]carbazoles

The cycloaddition between N‐protected 3‐{1‐[(trimethylsilyl)oxy]ethenyl}‐1H‐indoles and substituted maleimides (= 1H‐pyrrole‐2,5‐diones) yielded substituted pyrrolo[3,4‐a]carbazole derivatives bearing an additional succinimide (= pyrrolidine‐2,5‐dione) moiety either at C(5a) or C(10b) depending on the type of the protection group at the indole N‐atom. Derivatives substituted at C(10b) were isolated when the protection group, Me₃Si or Boc (^tBuOCO), was eliminated during the reaction (Schemes 2 and 3), whereas a substitution at C(5a) was observed when an electron‐withdrawing group, Tos (4‐MeC₆H₄SO₂) or pivaloyl (Me₃CCO), was not eliminated (Scheme 1). Complex results were found in reactions between 1‐(trimethylsilyl)‐3‐{1‐[(trimethylsilyl)oxy]ethenyl}‐1H‐indole, in contrast to formerly reported results (Scheme 3). Some derivatives of 1H,5H‐[1,2,4]triazolo[1′,2 : 1,2]pyridazino[3,4‐b]indole‐1,3(2H)‐dione were obtained from reactions with 4‐phenyl‐3H‐1,2,4‐triazole‐3,5(4H)‐dione (Scheme 2). All structures were established by spectroscopic data, by calculations, and one representative structure was confirmed by an X‐ray crystallographic analysis (Fig.). Finally, the formation of the different structure types was discussed, and compared with similar reactions reported in the literature.     

Structural Characterization of a Benzoxazinophenoxazine Formed as a By‐Product During the Synthesis of a 3‐Amino‐N,N‐dimethylsalicylamide

Several highly colored by‐products were observed chromatographically during the synthesis of 3‐amino‐N,N‐dimethylsalicylamide. One of these, an oxidative dimerization products, bis‐(N,N‐dimethylcarboxamido)‐aminophenoxazinone, was previously isolated and characterized. A tris‐(N,N‐dimethylcarboxamido)‐benzoxazino[3,2‐b]phenoxazine, presumably a higher oxidation or further reaction product of the previously isolated and characterized 2‐amino‐3 H ‐phenoxazin‐3‐one, has also been isolated and characterized by mass spectrometry and multinuclear NMR methods. We now wish to communicate the results of that structure characterization effort.     

Vibratilicin: a Novel Compound from the Basidiomycete Cortinarius vibratilis

A novel N‐containing compound, vibratilicin (=3‐[3‐(dimethylamino)‐4‐(hydroxyamino)‐4‐oxobutoxy]‐2‐(palmitoyloxy)propyl (9E,12E)‐octadeca‐9,12‐dienoate; 1 ), was isolated from the fruiting bodies of the basidiomycete Cortinarius vibratilis Fr. Compound 1 is a representative of the rare natural products containing hydroxamic acid moieties, and can be viewed as a derivative of neoengleromycin ( 2 ). Also isolated from the same fungus were five known compounds: ergosta‐5,7,22‐trien‐3β‐ol, 5α,8α‐epidioxyergosta‐6,22‐dien‐3β‐ol, p‐anisic acid, N‐(2‐hydroxyhexadecanoyl)‐4‐sphingenine, and (4E,8E)‐2‐N‐(2′‐hydroxypalmitoyl)‐1‐O‐(β‐D ‐glucopyranosyl)‐9‐methyl‐4,8‐sphingadienine. Their structures were determined mainly spectroscopically, including 2D‐NMR techniques (HMBC, HMQC, ¹H,¹H‐COSY).     

Structural and spectral assignment by 2D NMR of a new prenylated benzopyrancarboxylic acid and structural reassignment of a related compound

A new prenylated benzopyrancarboxylic acid, 1a (3,4‐dihydro‐5‐hydroxy‐2,7‐dimethyl‐8‐(2‐methyl‐2‐butenyl)‐ 2‐(4‐methyl‐1, 3‐pentadienyl)‐2H‐1‐benzopyran‐6‐carboxylic acid) was isolated from Peperomia amplexicaulis and fully characterized by 1D and 2D NMR and high‐resolution mass spectrometry. In the course of this investigation, the structure of a related compound (minus the carboxylic acid group) which was previously assigned as 2b was corrected to structure 1b . Copyright © 2003 John Wiley & Sons, Ltd.     

Direct patterning of poly(amic acid) and low‐temperature imidization using a crosslinker,a photoacid generator,and a thermobase generator

A positive‐type photosensitive polyimide (PSPI) based on poly(amic acid) (PAA), a crosslinker 1,1,1‐tris{4‐[2‐(vinyloxy)ethoxy]phenyl}ethane (TVPE), a photoacid generator (PAG) (5‐propylsulfonyloxyimino‐5H‐thiophen‐2‐ylidene)‐2‐(methylphenyl)acetonitrile (PTMA), and a thermobase generator (TBG) t‐butyl 2,6‐dimethylpiperidine‐1‐carboxylate (BDPC) has been developed as a promising material in microelectronics. The PAA was prepared from 3,3′,4,4′‐biphenyltetracarboxylic dianhydride (BPDA) and 4,4′‐oxydianiline (ODA) in dimethyl sulfoxide (DMSO). The PSPI, consisting of PAA (69 wt %), TPVE (21 wt %), PTMA (3 wt %), and BDPC (7 wt %), showed high sensitivity of 21 mJ/cm² and a high contrast of 6.8 when it was exposed to a 436‐nm line (g‐line), postbaked at 90 °C for 5 min, and developed with 1.69 wt % TMAHaq. A clear positive image of 8 μm line and space pattern was printed on film, which was exposed to 50 mJ/cm² of g‐line by a contact printing mode and fully converted to the corresponding polyimide (PI) pattern on heating at 200 °C, confirmed by FTIR spectroscopy. Thus, this system will be a good candidate for next generation PSPIs. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 3362–3369, 2009     

Hydrophilic graft modification of a commercial crystalline polyolefin

Hydroxy‐functionalized isotactic poly(1‐butene) was synthesized using transition metal‐catalyzed regioselective C? H borylation at the side chain of the commercial polyolefin and subsequent oxidation of the boronic ester functionality. Functionalization up to ～ 19 mol % of the termini of the ethyl side chain occurred without significant side reactions that could alter the polymer chain length. Esterification of the hydroxy group in the polymer with 2‐bromoisobutyl bromide generated a side chain‐functionalized polyolefin macroinitiator. Atom transfer radical polymerization of tert‐butyl acrylate from the macroinitiator produced a high molecular‐weight graft copolymer of the polyolefin, isotactic poly(1‐butene)‐graft‐poly(tert‐butyl acrylate) (PB‐g‐PtBA). Finally, the hydrolysis of the tert‐butoxy ester group of PB‐g‐PtBA created an amphiphilic polyolefin, isotactic poly(1‐butene)‐graft‐poly(acrylic acid), which contained a short carboxylic acid‐functionalized polymer block at the side chain. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 3533–3545, 2008     

N‐N migration of a carbamoyl group in a pyrazole derivative revealed by NMR

During a synthesis of 5‐amino‐4‐(6‐methoxy‐2‐methylpyridin‐3‐yl)‐3‐methyl‐1H‐pyrazole‐1‐carboxamide (see Scheme 1), a side‐reaction produced 3‐amino‐4‐(6‐methoxy‐2‐methylpyridin‐3‐yl)‐5‐methyl‐1H‐pyrazole‐1‐carboxamide as a by‐product that forms an equilibrium with the target‐compound. The structure of the by‐product was elucidated by the interpretation of 1D and 2D (HMQC, HMBC) NMR data where ¹H‐¹⁵ N HMBC correlations revealed the position of carbamoyl group attachment on the pyrazole. Comparison of structures of the target‐compound and the by‐product showed that the latter resulted from N‐N migration of the carbamoyl group in the target‐compound. Copyright © 2013 John Wiley & Sons, Ltd.     

Identification of the Structural Determinants for Anticancer Activity of a Ruthenium Arene Peptide Conjugate

Organometallic Ru(arene)–peptide bioconjugates with potent in vitro anticancer activity are rare. We have prepared a conjugate of a Ru(arene) complex with the neuropeptide [Leu⁵]‐enkephalin. [Chlorido(η⁶‐p‐cymene)(5‐oxo‐κO‐2‐{(4‐[(N‐tyrosinyl‐glycinyl‐glycinyl‐phenylalanyl‐leucinyl‐NH₂)propanamido]‐1H‐1,2,3‐triazol‐1‐yl)methyl}‐4H‐pyronato‐κO)ruthenium(II)] ( 8 ) shows antiproliferative activity in human ovarian carcinoma cells with an IC₅₀ value as low as 13 μM , whereas the peptide or the Ru moiety alone are hardly cytotoxic. The conjugation strategy for linking the Ru(cym) (cym=η⁶‐p‐cymene) moiety to the peptide involved N‐terminal modification of an alkyne‐[Leu⁵]‐enkephalin with a 2‐(azidomethyl)‐5‐hydroxy‐4H‐pyran‐4‐one linker, using Cu^I‐catalyzed alkyne–azide cycloaddition (CuAAC), and subsequent metallation with the Ru(cym) moiety. The ruthenium‐bioconjugate was characterized by high resolution top‐down electrospray ionization mass spectrometry (ESI‐MS) with regard to peptide sequence, linker modification and metallation site. Notably, complete sequence coverage was obtained and the Ru(cym) moiety was confirmed to be coordinated to the pyronato linker. The ruthenium‐bioconjugate was analyzed with respect to cytotoxicity‐determining constituents, and through the bioconjugate models [{2‐(azidomethyl)‐5‐oxo‐κO‐4H‐pyronato‐κO}chloride (η⁶‐p‐cymene)ruthenium(II)] ( 5 ) and [chlorido(η⁶‐p‐cymene){5‐oxo‐κO‐2‐([(4‐(phenoxymethyl)‐1H‐1,2,3‐triazol‐1‐yl]methyl)‐4H‐pyronato‐κO}ruthenium(II)] ( 6 ) the Ru(cym) fragment with a triazole‐carrying pyronato ligand was identified as the minimal unit required to achieve in vitro anticancer activity.