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Robinson′s synthesis has long been a classic in organic chemistry due to its simplicity and impact in the industry. Various modifications have been made to improve the system. Among them, replacing acetone with more acidic chemical equivalents such as calcium dicarboxylic acid or ethyl dicarboxylic acetone improved the yield. In line with this trend, our group previously reported the synthesis of mono- and di-N-substituted tropinone derivatives from the one-pot reaction of 2,5-dimethoxy tetrahydrofuran and various amines with acetonedicarboxylic acid in the presence of HCl and water at room temperature. In this study, the synthesis with acetone instead of acetone-dicarboxylic acid was examined. Mono- and di-N-substituted nortropinones were prepared in higher yields in all cases although there were extent to which yields increased depending on the nature of substituents

Biaryl diketones were synthesized via palladium-catalyzed carbonylative coupling in the presence of a palladium N-heterocyclic carbene complex and CO or metal carbonyls. Different arylboronic acids along with various CO-releasing molecules were tested to study the influence of structure. Generally, steric hindrance of arylboronic acids and CO-releasing ability of various metal carbonyls played significant roles. In most cases, single ketone products were found as the side products rather than direct coupling products.

luminescence (CL) flow injection system. The CL intensities of polyphenols are considerably weaker than those of luminal and acridinium ester, which are representative CL compounds. Hence, trans-4-(3-propionic acid) phenylboronic acid and 4-biphenylboronic acid in the presence of peroxidase or 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide have been used as an enhancer for highly sensitive polyphenol CL determination. However, methods to derive polyphenols with strong CL intensity have not been reported yet. 18 In recent times, after a new polymer, poly(amidoamine) dendrimer, was synthesized, dendrimers have been applied to material engineering based on optics in nanoscale science. The poly(propylene amine) family that was functionalized in the periphery with fluorescent dansyl units interacts with Co 2+ . More recently, acridinium dendrimers have been conjugated with bovine serum albumin, and its CL was estimated to be six times that of the acridinium salt. In this paper, we report the design of new types of polyphenol dendrimers having an increased number of chemiluminophores for high CL intensity; they also have hydroxyl groups in their periphery to form hydrogen bonds with an analyte. Polyphenol dendrimers having GA in the periphery were synthesized, and their CL was measured. We synthesized first-generation polyphenol dendrimers with GA units in the periphery by employing a divergent method using phenol, pyrocatechol, resorcinol, hydroquinone, 1,2,4-tri

phenol yielded 2a in 80%. After the debenzylation of 2a, we were able to separate 3a and the byproduct by chromatographic purification. Therefore, the desired zero-generation ester 3a was not isolated. Compounds 4a and 5a were synthesized by repeating this esterification and debenzylation, respectively, but the yield of the first-generation ester 5a was 91%. The esteri- fication of 3,4,5-trihydroxybenzoyl chloride with pyrocatechol, 3,4,5-trihydroxybenzoyl chloride with resorcinol, and 3,4,5- trihydroxybenzoyl chloride with hydroquinone yielded 2b (95%), 2c (96%), and 2d (91%), respectively. The zero-gene- ration esters 3b, 3c, and 3d and first-generation esters 5b, 5c, and 5d were synthesized as described above. The yields of the polyphenol dendrimers decreased with increasing dendrimer

A new Rh(I)-catalyzed tandem conjugate addition-Mannich cyclization reaction of imine-substituted electron-deficient alkenes with arylboronic acids has been developed to afford 2,3,4-trisubstituted 1,2,3,4-tetrahydroquinolines. This is the first example involving imine group as a secondary electrophile in Rh(I)-catalyzed tandem reactions.

Benzodiazepines are interesting compounds because of their pharmacological properties. Many members of this family are, in fact, nowadays widely used as tranquilizing and anticonvulsant agents. Although the first benzodiazepine was introduced as a drug nearly 30 years ago, the research in this area is still very active and is directed towards the synthesis of compounds of enhanced pharmacological activity. Some benzodiazepine derivatives are also used in industry, such as in photography (as dyes for acrylic fibers), and also as anti-inflammatory agents. 1H-1,5Benzodiazepines are used as starting materials for the preparation of some fused ring benzodiazepine derivatives, such as triaxol and oxadiazol. Despite their wide range of pharmacological activity, industrial and synthetic application, the synthesis of 1H-1,5-benzodiazepines has received little attention. As a part of research program related to the synthetic study of pharmacologically interesting benzodiazepine compounds, herein we now report the synthesis of 1H-1,5-benzodiazepine derivatives with heteroaromatic ketones (2-acetylfuran 2a, 2-acetylthiophene 2b, 2-acetylpyridine 2c, 3-acetylpyridine 2d, and 4-acetylpyridine 2e) by using conc-HCl, SiO2, or polyphosphoric acid (PPA) (Scheme 1). Specially we report synthesis of quinoxaline derivatives with phenylenediamine 1a and acetylpyridines 2c, 2e in aqueous 10% conc-HCl solution (Scheme 2). Moreover we describe the structural analysis of 7-chloro2,2,4-trimethyl-2,3-dihydro-1H-1,5-benzodiazepine 3f and 8-chloro-2,2,4-trimethyl-2,3-dihydro-1H-1,5-benzodiazepine 3g synthesized by 4-chloro-1,2-phenylenediamine 1b with acetone. Earlier we reported the synthesis of 2,4,4,-trimethyl-3H-5hydro-1,5-benzodiazepine and 2,4-diphenyl-4-methyl-3H-5hydro-1,5-benzodiazepine by using various reagents instead of PPA. When 1a was treated with 2a in the presence of PPA at 4045 °C for 5 h, a yellow crystalline solid, 3a was isolated

In order to synthesize new bioactive compounds and contrasting agents, reactions of glycine and glutamic acid as an animo acid with paraformaldehyde and hypophosphorous acid were executed. Products are 3,7-dihydroxy-3,7-dioxoperhydro-1,5,3,7-diazadiphosphocine-1,5-diacetic acid 1 and 3,7-dihydroxy-3,7-dioxoperhydro-1,5,3,7-diazadiphosphocine-1,5-di-(2-glutaric acid) 3. 2-[5-(1,2-Dicarboxyethyl)-3,7-dihydroxy-3,7-dioxo-315.715-[1,5,3,7] diazadiphosphocan-1-yl]-succinic acid 2 by using aspartic acid was not obtained. Esterification of 3,7-dihydroxy-3,7-dioxoperhydro-1,5,3,7-diaza-diphosphocine-1,5-diacetic acid 1 by treatment of methanol, ethanol, and propanol were executed. 3,7-Dihydroxy-3,7-dioxoperhydro-1,5,3,7-diazadiphosphocine-1,5-diacetic acid methyl ester 4, 3.7-dihydroxy-3,7-dioxoperhydro-1,5,3, 7-diazadiphosphocine-1.5-diacetic acid ethyl ester 5, and 3,7-dihydroxy-3,7-dioxoperhydro-1,5,3,7-diazadiphosphocine-1,5-diacetic acid propyl ester 6 were respectively synthesized in good yields. Continuously, we will try synthesis of novel compounds and evaluation of biological activity.

Cerulenin, a fatty acid synthase (FAS) inhibitor, induces apoptosis of variety of tumor cells. To elucidate mode of action by cerulenin, we employed the proteomics approach using Schizosaccharomyces pombe. The differential protein expression profile of S. pombe revealed that cerulenin modulated the expressions of proteins involved in stresses and metabolism, including both ade10 and adk1 proteins. The nutrient supplementation assay demonstrated that cerulenin affected enzymatic steps transferring a phosphoribosyl group. This result suggests that cerulenin accumulates AMP and p-ribosyl-s-amino-imidazole carboxamide (AICAR) and reduces other necessary nucleotides, which induces feedback inhibition of enzymes and the transcriptional regulation of related genes in de novo and salvage adenine metabolic pathway. Furthermore, the deregulation of adenine nucleotide synthesis may interfere ribonucleotide reductase and cause defects in cell cycle progression and chromosome segregation. In conclusion, cerulenin induces apoptosis through deregulation of adenine nucleotide biosynthesis resulting in nuclear division defects in S. pombe.

Tropane alkaloids have received a great deal of attention because of their remarkable pharmaceutical significance. Therefore a variety of synthetic approaches to tropane alkaloids have been investigated. Especially, a series of tropanes showed anticonvulsant activity against pentylenetetrazol-induced convulsions in mice and antiarrhythmic activity in rabbit previously treated with ouabain. *Corresponding Author. E-mail : As a part of a research program related to the synthetic study of pharmacologically interesting tropane compounds, we now report the synthesis of di-(N-tropinonyl)benzenes and di-(N-tropinonyl)alkanes in the reaction of phenylenediamines (or diaminoalkanes) with 2,5-dimethoxytetrahydrofuran, and acetonedicarboxylic acid at 0 C. Earlier we reported the synthesis of N-substituted nortropinones in the reaction of amines with 2,5-dimethoxytetrahydrofuran, and acetonedicarboxylic acid. A representative experimental procedure for the synthesis of 1,4-di-(8-azabicyclo[3,2,1]octan-3-onyl)benzene (7) is as follows: A mixture of 2,5-dimethoxytetrahydrofuran (6.6 g, 0.05 mol), acetonedicarboxylic acid (5.84 g, 0.04 mol), water (20 mL), and c-HCl (0.5 mL) was stirred for 30 min. p-Phenylenediamine (2.16 g, 0.02 mol) in water (10 mL) was added by using a dropping funnel at 0 C. After the reaction mixture was stirred under N2 at room temperature for 22 h, a crude brown solid was precipitated. The reaction mixture was diluted with water (20 mL) and neutralized with saturated NaHCO3 solution. The neutralized solution was extracted with dichloromethane (100 mL × 3). The organic layer was dried (Na2SO4), filtered and concentrated. The residue was chromatographed on a silica gel (n-hexane : ethyl acetate = 1 : 3, v/v) to yield 7 (4.47 g, 69%) as a brown crystalline solid. H-NMR showed a singlet at δ 4.49 for four protons of C1 and C5, a doublet at δ 1.78 for four protons of C6n and C7n, a doublet at δ 2.17 for four protons of C6x and C7x, a doublet at δ 2.22 (H-2(4)α, J = 3 Hz). for four protons of C2α and C4α, and a doublet at δ 2.70 (H-2(4)α, J = 10 Hz) for four protons of C2β and C4β. Aromatic protons were at δ 6.89 as a singlet.

Binding of N-formyl-methionyl-leucyl-phenylalanine (fMLP) to its specific cell surface receptor, N-formyl peptide receptor (FPR), triggers different cascades of biochemical events, eventually leading to cellular activation. However, the physiological role of fMLP and FPR during differentiation of mesenchymal stem cells is unknown. In this study, we attempted to determine whether fMLP regulates differentiation of mesenchymal stem cells derived from bone marrow. Analysis by quantitative-PCR and flow cytometry showed significantly increased expression of FPR1, but not FPR2 and FPR3, during osteoblastic differentiation. fMLP, a specific ligand of FPR1, promotes osteoblastic commitment and suppresses adipogenic commitment under differentiation conditions. Remarkably, fMLP-stimulated osteogenesis is associated with increased expression of osteogenic markers and mineralization, which were blocked by cyclosporine H, a selective FPR1 antagonist. In addition, fMLP inhibited expression of peroxisome proliferator-activated receptor-γ1, a major regulator of adipocytic differentiation. fMLP-stimulated osteogenic differentiation was mediated via FPR1-phospholipase C/phospholipase D-Ca(2+)-calmodulin-dependent kinase II-ERK-CREB signaling pathways. Finally, fMLP promoted bone formation in zebrafish and rabbits, suggesting its physiological relevance in vivo. Collectively, our findings provide novel insight into the functional role of fMLP in bone biology, with important implications for its potential use as a therapeutic agent for treatment of bone-related disorders.

The expression vector pWHM3-TR1R2, which contains sprT encoding Streptomyces griseus trypsin (SGT) and two positive regulatory genes (sgtR1 and sgtR2), was introduced into S. griseus IFO13350 and the productivity of SGT by the transformant was investigated in various media. Among the tested media, Ferm-0 gave 1.4 times more trypsin activity than C5/L medium. In addition, replacement of 2% glucose and 1% skim milk in Ferm-0 medium with 2% dextrin and 1% tryptone (named as Ferm-II medium) yielded significantly enhanced trypsin activity, by 4.1-fold, than that of Ferm-0. For simplifying the purification process, the cultural supernatant of S. griseus transformant in Ferm-II medium was fractionated with ammonium sulfate (25%-55%), and then applied to Hitrap benzamidine FF affinity column chromatography. The specific activity of the purified SGT by one-step column chromatography was 69,550 unit/mg protein, and the overall purification yield was above 8%, which was more effective than the methods of previous reports. The trypsin activity of the purified SGT was most active at pH 8.0 and 50 degrees C, and maintained their activities between pH 7.0 and pH 9.0, and up to 70 degrees C. These enzymatic properties were very similar to those of authentic eukaryotic trypsin purified from bovine pancreas.

A new Rh(I)-catalyzed tandem conjugate addition-Mannich cyclization reaction of imine-substituted electron-deficient alkenes with arylboronic acids has been developed to afford 2,3,4-trisubstituted 1,2,3,4-tetrahydroquinolines. This is the first example involving imine group as a secondary electrophile in Rh(I)-catalyzed tandem reactions.

Benzodiazepines are interesting compounds because of their pharmacological properties. Many members of this family are, in fact, nowadays widely used as tranquilizing and anticonvulsant agents. Although the first benzodiazepine was introduced as a drug nearly 30 years ago, the research in this area is still very active and is directed towards the synthesis of compounds of enhanced pharmacological activity. Some benzodiazepine derivatives are also used in industry, such as in photography (as dyes for acrylic fibers), and also as anti-inflammatory agents. 1H-1,5Benzodiazepines are used as starting materials for the preparation of some fused ring benzodiazepine derivatives, such as triaxol and oxadiazol. Despite their wide range of pharmacological activity, industrial and synthetic application, the synthesis of 1H-1,5-benzodiazepines has received little attention. As a part of research program related to the synthetic study of pharmacologically interesting benzodiazepine compounds, herein we now report the synthesis of 1H-1,5-benzodiazepine derivatives with heteroaromatic ketones (2-acetylfuran 2a, 2-acetylthiophene 2b, 2-acetylpyridine 2c, 3-acetylpyridine 2d, and 4-acetylpyridine 2e) by using conc-HCl, SiO2, or polyphosphoric acid (PPA) (Scheme 1). Specially we report synthesis of quinoxaline derivatives with phenylenediamine 1a and acetylpyridines 2c, 2e in aqueous 10% conc-HCl solution (Scheme 2). Moreover we describe the structural analysis of 7-chloro2,2,4-trimethyl-2,3-dihydro-1H-1,5-benzodiazepine 3f and 8-chloro-2,2,4-trimethyl-2,3-dihydro-1H-1,5-benzodiazepine 3g synthesized by 4-chloro-1,2-phenylenediamine 1b with acetone. Earlier we reported the synthesis of 2,4,4,-trimethyl-3H-5hydro-1,5-benzodiazepine and 2,4-diphenyl-4-methyl-3H-5hydro-1,5-benzodiazepine by using various reagents instead of PPA. When 1a was treated with 2a in the presence of PPA at 4045 °C for 5 h, a yellow crystalline solid, 3a was isolated

The tropane class of alkaloids has continued to elicit the unabated interests among organic chemists because of their pharmacological significance, and a great deal of efforts has been focused on the stereochemical synthetic methodologies. Cocaine, a notorious member of this alkaloidal family, is found in erythroxylon coca, indigenous to the higher elevations of peru. The natives of this region, descendants of the Incas, still chew the coca leaf for its stimulatory properties. In particular, a series of tropans showed anticonvulsant activity against pentylenetetrazolinduced convulsions in mice and antiarrhythmic activity in rabbit previously treated with ouabain. As a part of ongoing research for the pharmacologically interesting tropane compounds, herein we report a new synthetic conditions of corresponding 2-substituted 8-azabicyclo[3.2.1]octan-3-one, 3, by aldol condensation from 8substituted 8-azabicyclo[3.2.1]octan-3-one, 1. We already reported a synthesis of 2,4-disubstituted 8-azabicyclo[3.2.1]octan-3-one, 2, derived from the reaction of N-substituted 8azabicyclo[3.2.1]octan-3-one, 1, with aldehydes (R1CHO) in the presence of ethanol and aqueous 5 N NaOH. We also reported the synthesis of di-(N-tropinonyl)alkanes from the reaction of phenylenediamines (or diaminoalkanes) with 2,5-dimethoxytetrahydrofuran and acetonedicarboxylic acid. Then our attempt to prepare 2-substituted 8-azabicyclo[3.2.1]octan-3-one, 3, from 8-substituted 8-azabicyclo[3.2.1]octan-3-one, 1, was unsuccessful, under various reaction conditions: sodium hydride, sodium methoxide, or butyl lithium. But M. Majewski and R. Lazny reported that their synthesized compound, 2-benzylidene-8-methyl-8-azabicyclo[3.2.1]octan-3-one was done through three-step treatment of chiral lithium amide, Ac2O, and SiO2 (Scheme 1). In brief, as their synthetic method had three-step reactions and three times work-ups, it was so complicated. Recently, Peter A. Crooks et al. reported two-step synthesis by treatment of lithium diisopropylamide or lithium bis(trimethylsilyl)amide. In order to synthesize 2-substituted 8-azabicyclo[3.2.1]octan-3-one, 3, simply and efficiently, we conducted research on the effect of aqueous NaOH concentration variations (1 N, 0.5 N, 0.1 N, 0.02 N, or 0.01 N). Yield comparison of compound 3e according to concentration variation of aqueous NaOH solution is expressed in Table 1. In case of higher concentrations over aqueous 0.01 N NaOH solution, the ratio of 2,4-disubstituted 8-azabicyclo[3.2.1]octan-3-one, 2, was produced somewhat higher than that of 2-substituted 8-azabicyclo[3.2.1]octan-3-one, 3. Yield of 8-benzylidene-8-phenyl-8-azabicyclo[3.2.1]octan