To a solution of 2-bromo-2-cyclohexn-1-ol (2.45 g, 13.8 mmol) in N,N-dimethylformamide (12 mL) we... more To a solution of 2-bromo-2-cyclohexn-1-ol (2.45 g, 13.8 mmol) in N,N-dimethylformamide (12 mL) were added imidazole (1.89 g, 27.8 mmol) and tert-butyldimethylsilyl (TBS) chloride (2.15 g, 13.8 mmol). The reaction mixture was stirred at room temperature for 12 h and then aqueous hydrochloric acid (5%, 20 mL) was added. The resulting mixture was extracted with diethyl ether (2 x 30 mL), and the combined organic layers were washed with brine (2 x 50 mL), and dried (Na 2 SO 4). The solvent was removed under reduced pressure to give a colorless oil, which was purified by silica gel flash column chromatography using hexanes/ethyl acetate (7/1) as the eluent to give TBS ether 9 as a colorless oil (3.95 g, 98%): R f (hexanes/ethyl acetate, 15/1) 0.50; 1 H NMR (360 MHz, CDCl 3) δ 0.11 (s, 3H), 0.17 (s,
A solution of 1 (105 mg, 0.99 mmol) in carbon tetrachloride (2 mL) was added under argon to a sol... more A solution of 1 (105 mg, 0.99 mmol) in carbon tetrachloride (2 mL) was added under argon to a solution of freshly sublimed tetracyanoethylene (127 mg, 0.99 "01) in the same solvent (2 mL) at room temperature. Initially, a bright mauve color was observed. After being stirred for 2 days, the reaction mixture was filtered through a bed of Celite, which was rinsed with carbon tetrachloride. Evaporation of the filtrate provided 63 mg (27%) of 14 as a white crystalline solid. Following recrystallization from chloroform and sublimation (90 "C and 0.05 torr), the adduct exhibited a decomposition point of 182 "C: 'H
from 1,4-Bis(tert-butylthio)-1,3-butadiene Precursors.-A highly efficient one-step method using f... more from 1,4-Bis(tert-butylthio)-1,3-butadiene Precursors.-A highly efficient one-step method using functionalized protected dithiols of type (III) as precursors for the synthesis of 3,6-disubstituted dithiins is presented. Dithiols (IIIa) and (IIIb) are easily converted into derivatives (IIId)-(IIIf).-(KOREEDA,
Journal of the American Chemical Society, Dec 1, 1970
Ajugalactone, an Insect Moulting Inhibitor as Tested by the Chilo Dipping Method Sir : An extensi... more Ajugalactone, an Insect Moulting Inhibitor as Tested by the Chilo Dipping Method Sir : An extensive effort to search for antiecdysones has resulted in the discovery' of several plants containing compounds which inhibit moulting of Chilo suppressalis (rice-stem borer) according to the dipping method. We assign structure 1 to the first of such compounds, ajugalactone. The crude polyhydroxysteroid fraction3 obtained from the methanol extract of 2 kg of the entire plant of Ajuga decumbens THUNB ("kiranso" in Japanese) was chromatographed on alumina and (
Proton nuclear magnetic resonance (l H NMR) spectra were recorded on a Varian Inova-400 (400 MHz)... more Proton nuclear magnetic resonance (l H NMR) spectra were recorded on a Varian Inova-400 (400 MHz), or a Varian Inova-500 (500 MHz) FT NMR spectrometer. Carbon-13 nuclear magnetic resonance (13 C NMR) spectra were recorded on a Varian Inova-400 (100.6 MHz) or a Varian Inova-500 (125.8 MHz) FT NMR spectrometer. The solvent used for NMR spectroscopy was chloroform-d l (CDC1 3). Chemical shifts are reported in δ units with respect to tetramethylsilane (δ = 0.00) as internal standard. Coupling constants (J values) are given in hertz (Hz). The following abbreviations are used to describe peak patterns: "s" for singlet, "d" for doublet, "t" for triplet, "q" for quartet, "m" for multiplet, "br" for broadened, and "ABq" for the two-spin AB system. NMR data are presented as follows: chemical shift (multiplicity, integrated intensity, and coupling constant). Infrared (IR) spectra were recorded on a Nicolet Model 5-DX FT-IR spectrometer using sodium chloride plates (liquid) or potassium bromide pellets (solid). Data are reported in wave numbers (cm-1). Flash column chromatography was performed by the method of Still 1 using Merck 230-400 mesh silica gel. Analytical thin layer chromatography (TLC) was perfomed using EM Science Silica Gel 60 F 254 precoated on Aluminium Sheet. Compounds were visualized using ultraviolet light, basic aqueous potassium permanganate, or ceric ammonium sulfate/sulfuric acid. Solvents were freshly distilled prior to use. Diethyl ether (Et 2 O) and tetrahydrofuran (THF) were distilled from sodium/benzophenone ketyl. Dichloromethane (CH 2 Cl 2), triethylamine (Et 3 N) were distilled from calcium hydride. Benzene and toluene were distilled from sodium metal. 2 n-Butyllithium was purchased from Aldrich Chemical Company and titrated using the method of Kofron. 2 All other reagents were used as received, distilled, or recrystallized as necessary. All air-or moisture-sensitive reactions were conducted in oven-or flame-dried glassware, and under an atmosphere of argon. Moisture-sensitive reagents were transferred through rubber septa using syringes or cannulas. 1,4-Dioxaspiro[4.5]dec-7-ene O O This known ketal 3 was synthesized by modification of Lambert s procedure. 4 To a 500-mL round-bottom flask were added 1-methoxycyclohexa-1,4-diene (2,5-dihydroanisole) (85% tech. grade, 11.0 g, 85 mmol), ethylene glycol (12.4 g, 200 mmol) and a catalytic amount of p-TsOH¥H 2 O (208 mg, 1.0 mmol) and CH 2 Cl 2 (200 mL). The reaction was complete after stirring at room temperature for 12 h as indicated by the tlc analysis. The reaction mixture was then washed with, successively, saturated aqueous NaHCO 3 (50 mL), water (50 mL), and brine (50 mL). The organic layer was dried over MgSO 4 and the solvent was removed by rotary evaporation. Purification of the oily residue thus obtained by silica gel flash column chromatography using 1 : 8 hexanes/ethyl acetate as the eluting solvent afforded the ketal as a clear liquid (11.9 g, quantitative). Identity of this ketal product was ascertained by comparison of the 1 H NMR spectrum with that reported in the literature. 3 8-(4-Chloro-phenylselanyl)-1,4-dioxa-spiro[4.5]decan-7-ol (12) 12 Krief s procedure was followed. 5 To a 25-mL round-bottom flask containing THF (5 mL) were added bis(4-chlorophenyl) diselenide (0.57 g, 1.5 mmol) and NaH (60% in mineral oil, 0.25 g, 6.2 mmol). The reaction mixture was then heated at reflux (bath temp. 80 ¡C) for 1 1 / 2 h during which time a brown suspension was generated.
ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was e... more ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was e... more ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
The mutagenicity in Salmonella and in vivo sister chromatid exchange in the bone-marrow cells of ... more The mutagenicity in Salmonella and in vivo sister chromatid exchange in the bone-marrow cells of mice was determined for 1,4-, 1,3-, 2,4-, and 3,4-dimethylphenanthrene (DMPh) with the objective to study the relative importance of substitution at the 1 and 4 positions of this series of methylated phenanthrenes. For both tests, 1,4- DMPh was decidedly more genotoxic than the remaining regioisomers. While the well recognized role of steric crowding in the bay region is a factor in this enhanced genotoxicity, equally important is substitution at the 1 position with its potential to inhibit detoxication through 9,10-diol formation.
15 Cyclohexane epoxide derivatives were synthesized and compared for direct mutagenicity and bact... more 15 Cyclohexane epoxide derivatives were synthesized and compared for direct mutagenicity and bacterial toxicity using Salmonella typhimurium strain TAIOO in the liquid suspension and spot-test version of the Ames procedure. While no general correlations could be established for position and stereochemistry of the hydroxylated derivatives, an increase in mutagenicity was noted for the presence of electron-withdrawing groups and unsaturation in conjugation with the oxirane groups.
The biological activities of benzo(a)pyrene, cyclopenta(c,d)pyrene, and 12 other structurally rel... more The biological activities of benzo(a)pyrene, cyclopenta(c,d)pyrene, and 12 other structurally related compounds were assessed by mutagenicity studies with bacterial and mammalian cells and/or skin tumorigenicity studies with mice. The ability of the parent hydrocarbons to be metabolically activated to mutagenic products was examined in strains TA98 and TA100 of Salmonella typhimurium, using 3 experimental protocols. In each case, cyclopenta(c,d)pyrene was metabolically activated to products mutagenic to the bacteria to a greater extent than was benzo(a)pyrene. However, 7,8-dihydrobenzo(a)pyrene and 0,10-dihydrobenzo(e)pyrene were the best substrates for metabolic activation to bacterial mutagens. Highly purified epoxide hydrase added to a purified and reconstituted monooxygenase system readily abolished the mutagenic activity observed in strain TA100 of S. typhimurium when cyclopenta(c,d)pyrene was the substrate, but not when benzo(a)pyrene was the substrate. Inherent mutagenicity of several epoxides of the hydrocarbons generally paralleled the ability of their potential metabolic precursors to be activated to mutagens. 1-Pyrenyloxirane and 10,11-dihydrocycloheptapyrene 8,9-oxide were highly mutagenic in strains TA98 and TA100 of S. typhimurium, and in the former strain these activities were comparable to that observed with 9,10-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene, 4-Pyrenyloxirane was significantly less mutagenic than was 1-pyrenyloxirane in both strains of bacteria and in mammalian cells. Benzo(a)pyrene was over 20 times more tumorigenic than was cyclopenta-(c,d)pyrene, and it was the most potent of the 11 compounds tested for tumor-initiating activity in 2-stage initiation-promotion experiments on the skin of mice. Cyclopenta(c,d)pyrene had tumor-initiating activity comparable to that of benzo-(a)anthracene, but it was significantly less active than chrysene. Thus, contrary to inferences made from its high mutagenic activity, cyclopenta(c,d)pyrene is a weak tumor initiator on mouse skin.
The sterlc and stereochemical factors which favor the 5exo cyclization of a 5-substituted 2-sila-... more The sterlc and stereochemical factors which favor the 5exo cyclization of a 5-substituted 2-sila-Shexen-l-y1 radical have been probed. This radical cyclization approach constitutes a highly efficient and convenient means for the stereospecfic introduction of an angular hydroxymethyl group.
A stereospecific, highly efficient, generally applicable synthesis of z-ard El-alkoxy-1,3-butadie... more A stereospecific, highly efficient, generally applicable synthesis of z-ard El-alkoxy-1,3-butadienes involving dehydrative decarboxylations of 4,5_unsaturated-2-alkoxy-3-hydroxy-carboxylic acids is described.
To a solution of 2-bromo-2-cyclohexn-1-ol (2.45 g, 13.8 mmol) in N,N-dimethylformamide (12 mL) we... more To a solution of 2-bromo-2-cyclohexn-1-ol (2.45 g, 13.8 mmol) in N,N-dimethylformamide (12 mL) were added imidazole (1.89 g, 27.8 mmol) and tert-butyldimethylsilyl (TBS) chloride (2.15 g, 13.8 mmol). The reaction mixture was stirred at room temperature for 12 h and then aqueous hydrochloric acid (5%, 20 mL) was added. The resulting mixture was extracted with diethyl ether (2 x 30 mL), and the combined organic layers were washed with brine (2 x 50 mL), and dried (Na 2 SO 4). The solvent was removed under reduced pressure to give a colorless oil, which was purified by silica gel flash column chromatography using hexanes/ethyl acetate (7/1) as the eluent to give TBS ether 9 as a colorless oil (3.95 g, 98%): R f (hexanes/ethyl acetate, 15/1) 0.50; 1 H NMR (360 MHz, CDCl 3) δ 0.11 (s, 3H), 0.17 (s,
A solution of 1 (105 mg, 0.99 mmol) in carbon tetrachloride (2 mL) was added under argon to a sol... more A solution of 1 (105 mg, 0.99 mmol) in carbon tetrachloride (2 mL) was added under argon to a solution of freshly sublimed tetracyanoethylene (127 mg, 0.99 "01) in the same solvent (2 mL) at room temperature. Initially, a bright mauve color was observed. After being stirred for 2 days, the reaction mixture was filtered through a bed of Celite, which was rinsed with carbon tetrachloride. Evaporation of the filtrate provided 63 mg (27%) of 14 as a white crystalline solid. Following recrystallization from chloroform and sublimation (90 "C and 0.05 torr), the adduct exhibited a decomposition point of 182 "C: 'H
from 1,4-Bis(tert-butylthio)-1,3-butadiene Precursors.-A highly efficient one-step method using f... more from 1,4-Bis(tert-butylthio)-1,3-butadiene Precursors.-A highly efficient one-step method using functionalized protected dithiols of type (III) as precursors for the synthesis of 3,6-disubstituted dithiins is presented. Dithiols (IIIa) and (IIIb) are easily converted into derivatives (IIId)-(IIIf).-(KOREEDA,
Journal of the American Chemical Society, Dec 1, 1970
Ajugalactone, an Insect Moulting Inhibitor as Tested by the Chilo Dipping Method Sir : An extensi... more Ajugalactone, an Insect Moulting Inhibitor as Tested by the Chilo Dipping Method Sir : An extensive effort to search for antiecdysones has resulted in the discovery' of several plants containing compounds which inhibit moulting of Chilo suppressalis (rice-stem borer) according to the dipping method. We assign structure 1 to the first of such compounds, ajugalactone. The crude polyhydroxysteroid fraction3 obtained from the methanol extract of 2 kg of the entire plant of Ajuga decumbens THUNB ("kiranso" in Japanese) was chromatographed on alumina and (
Proton nuclear magnetic resonance (l H NMR) spectra were recorded on a Varian Inova-400 (400 MHz)... more Proton nuclear magnetic resonance (l H NMR) spectra were recorded on a Varian Inova-400 (400 MHz), or a Varian Inova-500 (500 MHz) FT NMR spectrometer. Carbon-13 nuclear magnetic resonance (13 C NMR) spectra were recorded on a Varian Inova-400 (100.6 MHz) or a Varian Inova-500 (125.8 MHz) FT NMR spectrometer. The solvent used for NMR spectroscopy was chloroform-d l (CDC1 3). Chemical shifts are reported in δ units with respect to tetramethylsilane (δ = 0.00) as internal standard. Coupling constants (J values) are given in hertz (Hz). The following abbreviations are used to describe peak patterns: "s" for singlet, "d" for doublet, "t" for triplet, "q" for quartet, "m" for multiplet, "br" for broadened, and "ABq" for the two-spin AB system. NMR data are presented as follows: chemical shift (multiplicity, integrated intensity, and coupling constant). Infrared (IR) spectra were recorded on a Nicolet Model 5-DX FT-IR spectrometer using sodium chloride plates (liquid) or potassium bromide pellets (solid). Data are reported in wave numbers (cm-1). Flash column chromatography was performed by the method of Still 1 using Merck 230-400 mesh silica gel. Analytical thin layer chromatography (TLC) was perfomed using EM Science Silica Gel 60 F 254 precoated on Aluminium Sheet. Compounds were visualized using ultraviolet light, basic aqueous potassium permanganate, or ceric ammonium sulfate/sulfuric acid. Solvents were freshly distilled prior to use. Diethyl ether (Et 2 O) and tetrahydrofuran (THF) were distilled from sodium/benzophenone ketyl. Dichloromethane (CH 2 Cl 2), triethylamine (Et 3 N) were distilled from calcium hydride. Benzene and toluene were distilled from sodium metal. 2 n-Butyllithium was purchased from Aldrich Chemical Company and titrated using the method of Kofron. 2 All other reagents were used as received, distilled, or recrystallized as necessary. All air-or moisture-sensitive reactions were conducted in oven-or flame-dried glassware, and under an atmosphere of argon. Moisture-sensitive reagents were transferred through rubber septa using syringes or cannulas. 1,4-Dioxaspiro[4.5]dec-7-ene O O This known ketal 3 was synthesized by modification of Lambert s procedure. 4 To a 500-mL round-bottom flask were added 1-methoxycyclohexa-1,4-diene (2,5-dihydroanisole) (85% tech. grade, 11.0 g, 85 mmol), ethylene glycol (12.4 g, 200 mmol) and a catalytic amount of p-TsOH¥H 2 O (208 mg, 1.0 mmol) and CH 2 Cl 2 (200 mL). The reaction was complete after stirring at room temperature for 12 h as indicated by the tlc analysis. The reaction mixture was then washed with, successively, saturated aqueous NaHCO 3 (50 mL), water (50 mL), and brine (50 mL). The organic layer was dried over MgSO 4 and the solvent was removed by rotary evaporation. Purification of the oily residue thus obtained by silica gel flash column chromatography using 1 : 8 hexanes/ethyl acetate as the eluting solvent afforded the ketal as a clear liquid (11.9 g, quantitative). Identity of this ketal product was ascertained by comparison of the 1 H NMR spectrum with that reported in the literature. 3 8-(4-Chloro-phenylselanyl)-1,4-dioxa-spiro[4.5]decan-7-ol (12) 12 Krief s procedure was followed. 5 To a 25-mL round-bottom flask containing THF (5 mL) were added bis(4-chlorophenyl) diselenide (0.57 g, 1.5 mmol) and NaH (60% in mineral oil, 0.25 g, 6.2 mmol). The reaction mixture was then heated at reflux (bath temp. 80 ¡C) for 1 1 / 2 h during which time a brown suspension was generated.
ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was e... more ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was e... more ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
The mutagenicity in Salmonella and in vivo sister chromatid exchange in the bone-marrow cells of ... more The mutagenicity in Salmonella and in vivo sister chromatid exchange in the bone-marrow cells of mice was determined for 1,4-, 1,3-, 2,4-, and 3,4-dimethylphenanthrene (DMPh) with the objective to study the relative importance of substitution at the 1 and 4 positions of this series of methylated phenanthrenes. For both tests, 1,4- DMPh was decidedly more genotoxic than the remaining regioisomers. While the well recognized role of steric crowding in the bay region is a factor in this enhanced genotoxicity, equally important is substitution at the 1 position with its potential to inhibit detoxication through 9,10-diol formation.
15 Cyclohexane epoxide derivatives were synthesized and compared for direct mutagenicity and bact... more 15 Cyclohexane epoxide derivatives were synthesized and compared for direct mutagenicity and bacterial toxicity using Salmonella typhimurium strain TAIOO in the liquid suspension and spot-test version of the Ames procedure. While no general correlations could be established for position and stereochemistry of the hydroxylated derivatives, an increase in mutagenicity was noted for the presence of electron-withdrawing groups and unsaturation in conjugation with the oxirane groups.
The biological activities of benzo(a)pyrene, cyclopenta(c,d)pyrene, and 12 other structurally rel... more The biological activities of benzo(a)pyrene, cyclopenta(c,d)pyrene, and 12 other structurally related compounds were assessed by mutagenicity studies with bacterial and mammalian cells and/or skin tumorigenicity studies with mice. The ability of the parent hydrocarbons to be metabolically activated to mutagenic products was examined in strains TA98 and TA100 of Salmonella typhimurium, using 3 experimental protocols. In each case, cyclopenta(c,d)pyrene was metabolically activated to products mutagenic to the bacteria to a greater extent than was benzo(a)pyrene. However, 7,8-dihydrobenzo(a)pyrene and 0,10-dihydrobenzo(e)pyrene were the best substrates for metabolic activation to bacterial mutagens. Highly purified epoxide hydrase added to a purified and reconstituted monooxygenase system readily abolished the mutagenic activity observed in strain TA100 of S. typhimurium when cyclopenta(c,d)pyrene was the substrate, but not when benzo(a)pyrene was the substrate. Inherent mutagenicity of several epoxides of the hydrocarbons generally paralleled the ability of their potential metabolic precursors to be activated to mutagens. 1-Pyrenyloxirane and 10,11-dihydrocycloheptapyrene 8,9-oxide were highly mutagenic in strains TA98 and TA100 of S. typhimurium, and in the former strain these activities were comparable to that observed with 9,10-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene, 4-Pyrenyloxirane was significantly less mutagenic than was 1-pyrenyloxirane in both strains of bacteria and in mammalian cells. Benzo(a)pyrene was over 20 times more tumorigenic than was cyclopenta-(c,d)pyrene, and it was the most potent of the 11 compounds tested for tumor-initiating activity in 2-stage initiation-promotion experiments on the skin of mice. Cyclopenta(c,d)pyrene had tumor-initiating activity comparable to that of benzo-(a)anthracene, but it was significantly less active than chrysene. Thus, contrary to inferences made from its high mutagenic activity, cyclopenta(c,d)pyrene is a weak tumor initiator on mouse skin.
The sterlc and stereochemical factors which favor the 5exo cyclization of a 5-substituted 2-sila-... more The sterlc and stereochemical factors which favor the 5exo cyclization of a 5-substituted 2-sila-Shexen-l-y1 radical have been probed. This radical cyclization approach constitutes a highly efficient and convenient means for the stereospecfic introduction of an angular hydroxymethyl group.
A stereospecific, highly efficient, generally applicable synthesis of z-ard El-alkoxy-1,3-butadie... more A stereospecific, highly efficient, generally applicable synthesis of z-ard El-alkoxy-1,3-butadienes involving dehydrative decarboxylations of 4,5_unsaturated-2-alkoxy-3-hydroxy-carboxylic acids is described.
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Papers by Masato Koreeda