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Hideo Tanaka - One of the best experts on this subject based on the ideXlab platform.
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Chemo- and product-selective electrooxidation of 3-(arylthiomethyl)- Δ3-Cephems
Synthesis, 2009Co-Authors: Hideo Tanaka, Sigeru Torii, Yoshihisa Tokumaru, Ken-ichi Fukui, Manabu Kuroboshi, Anny Jutand, Christian AmatoreAbstract:Electrolysis of 3-arylthiomethyl-Δ 3 -Cephemspossessing various substituents on the arylthio moiety undergo chemoselective andproduct-selective electrooxidation to give several different products.These include isomeric mixtures of the corresponding methoxylatedCephems, a bis[(Δ 3 -Cephemspossessing various substituents on the arylthio moiety undergo chemoselective andproduct-selective electrooxidation to give several different products.These include isomeric mixtures of the corresponding methoxylatedCephems, a bis[(Δ 3 -Cephem-3-yl)methyl]disulfideor a 3-dimethoxymethyl-Δ 3 -Cephem-3-yl)methyl]disulfideor a 3-dimethoxymethyl-Δ 3 -Cephem. Theselectivity of the oxidation is highly dependent on the nature ofthe substituents on the arylthio moiety which suggests that bothsteric and electronic effects play an important role in the electrooxidationof 3-arylthiomethyl-Δ 3 -Cephem. Theselectivity of the oxidation is highly dependent on the nature ofthe substituents on the arylthio moiety which suggests that bothsteric and electronic effects play an important role in the electrooxidationof 3-arylthiomethyl-Δ 3 -Cephems.
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Reductive cross-coupling of 3-substituted delta 3-Cephems with alkenyl halides in an Al/PbBr2/NiBr2(bpy) triplemetal redox system. Synthesis of 3-alkenyl-delta 3-Cephems.
The Journal of organic chemistry, 2001Co-Authors: Hideo Tanaka, Jinfeng Zhao, Hiroshi KumaseAbstract:Synthesis of 3-alkenyl-delta 3-Cephems was performed successfully by cross-coupling 3-(trifluoromethylsulfonyloxy or chloro)-delta 3-Cephem with alkenyl halides, e.g., vinyl bromide, trans-1-bromo-1-propene, and trans-beta-bromostyrene in an Al/cat.PbBr2/cat.NiBr2(bpy)/NMP (or DMF) system. Reduction of 3-(trifluoromethylsulfonyloxy)-delta 3-Cephem into norcephalosporin was also achieved by a similar reaction in the presence of 5 molar equiv of water. Scope and a plausible mechanism of the Al/Pb/Ni triplemetal-redox promoted reactions are discussed.
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synthesis of 3 chloro δ3 Cephem 4 carboxylate by addition cyclization of allenecarboxylate copper ii promoted aerobic oxidation of arenesulfinic acids
Bulletin of the Chemical Society of Japan, 1996Co-Authors: Hideo Tanaka, Ryo Kikuchi, Sigeru ToriiAbstract:The selective transformation of allenecarboxylate derived from penicillin into 3-chloro-Δ3-Cephem-4-carboxylate was successfully achieved by an addition/cyclization reaction with chloride salts in aerobic media containing a copper(II) catalysts, in which copper(II)-catalyzed aerobic oxidation of in situ generated benzenesulfinate ion into less nucleophilic sulfonate ion prior to the nucleophilic addition of the former ion to the allenecarboxylate would completely eliminate the formation of undesired 3-phenylsulfonyl-Δ3-Cephem-4-carboxylate. Under similar aerobic conditions, arenesulfinates salts and arenesulfinic acids were smoothly oxidized to the corresponding sulfonate salts and sulfonic acids, respectively.
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Synthesis of 3-alkenyl-Δ2-Cephems by copper(I) chloride-promoted alkenylation of 3-trifluoromethylsulfonyloxy-Δ3-Cephem with alkenyltributyltins
Tetrahedron Letters, 1996Co-Authors: Hideo Tanaka, Shin-ichi Sumida, Sigeru ToriiAbstract:Abstract Synthesis of 3-alkenyl-Δ 2 -Cephems 3 was performed in regioselective manner by copper(I) chloride-promoted alkenylation of 3-trifluoromethylsulfonyloxy-Δ 3 -Cephem 1 with alkenyltributyltins. Subsequent Diels-Alder reaction of the 3-vinyl-Δ 2 -Cephem 3a with acrolein opened a new access to C(2) C(3) fused tricyclic cephalosporin 9 .
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TRANSFORMATION OF PENICILLINS INTO 3-SUBSTITUTED DELTA 3-CephemS THROUGH ADDITION/CYCLIZATION OF ALLENECARBOXYLATES
Bulletin of the Chemical Society of Japan, 1996Co-Authors: Hideo Tanaka, Shin-ichi Sumida, Yutaka Kameyama, Koichi Sorajo, Isao Wada, Shigeru ToriiAbstract:A straightforward synthesis of Δ3-Cephems 2 bearing heteroatom substituents directly attached to C(3)-position was performed successfully by a sequential addition/cyclization reaction of allenecarboxylate 4 derived from eithen penicillin 1. Upon treatment of the allenecarboxylate 4 with morpholine, pyrrolidine, sodium azide, and 5-methyl-1,3,4-thiadiazole-2-thiol in DMF in the presence of calcium chloride, the addition/cyclization reaction proceeded smoothly to afford the corresponding 3-substituted Δ3-Cephems 2a—e. Reaction of the allenecarboxylate 4 with lithium chloride in NMP (N-methyl-2-pyrrolidone) in the presence of aluminum chloride afforded 3-chloro-Δ3-Cephem 2f, while without aluminum chloride, 3-phenylsulfonyl-Δ3-Cephem 2e was mainly obtained. The 3-sulfenyl-Δ3-Cephems 12 were prepared by a similar addition/cyclization reaction of allenecarboxylates 10 with a catalytic amount of thiolates. The sulfenyl moieties attached at the sulfur atom of the C(4)-substituent of 10 were introduced at the C(3...
Enrico Domenici - One of the best experts on this subject based on the ideXlab platform.
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synthesis and preliminary biological evaluation of 3 substituted Cephem sulfones as potential β lactamase inhibitors
European Journal of Organic Chemistry, 2001Co-Authors: Francesco De Angelis, Giuseppe Attorrese, G. Cavicchio, Sabatino Ciampa, Alessandra Di Tullio, Daniela Fattori, Rosario Nicoletti, Enrico DomeniciAbstract:3′-Substituted Cephem sulfones, as well as the unsubstituted congener, were synthesized and biologically evaluated as β-lactamase inhibitors. Sodium 3′-substituted cephalosporanate sulfones 4 and 5 were prepared starting from 7-aminodeacetoxycephalosporanic acid (7-ADCA, 6) by a bromodeamination reaction, followed by reduction of the 7-halo derivative. Selective, radical bromination at C-3′ on the Δ3-isomer, followed by nucleophilic substitution and then retroisomerization at Δ2, afforded the required derivatives. 3′-Unsubstituted and 3′-acetoxyCephem sulfones 2 and 3 were prepared using routine chemistry. The 3′-substituted Cephem sulfone derivatives, evaluated as β-lactamase inhibitors by IC50 determinations, behave as weak inhibitors of the class D “oxacillinase” OXA1 from Escherichia coli and the class C β-lactamase of Enterobacter cloacae P99. Conversely, the 3′-unsubstituted Cephem sulfone 2 was shown to be comparable to sulbactam and even more active than clavulanic acid against the latter enzyme. The activity of 2 against E. cloacae P99 was also greatly enhanced by prolonging the pre-incubation time. Considerations as to the mechanism of inhibition are also put forward.
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Synthesis and Preliminary Biological Evaluation of 3′‐Substituted Cephem Sulfones as Potential β‐Lactamase Inhibitors
European Journal of Organic Chemistry, 2001Co-Authors: Francesco De Angelis, Giuseppe Attorrese, G. Cavicchio, Sabatino Ciampa, Alessandra Di Tullio, Daniela Fattori, Rosario Nicoletti, Enrico DomeniciAbstract:3′-Substituted Cephem sulfones, as well as the unsubstituted congener, were synthesized and biologically evaluated as β-lactamase inhibitors. Sodium 3′-substituted cephalosporanate sulfones 4 and 5 were prepared starting from 7-aminodeacetoxycephalosporanic acid (7-ADCA, 6) by a bromodeamination reaction, followed by reduction of the 7-halo derivative. Selective, radical bromination at C-3′ on the Δ3-isomer, followed by nucleophilic substitution and then retroisomerization at Δ2, afforded the required derivatives. 3′-Unsubstituted and 3′-acetoxyCephem sulfones 2 and 3 were prepared using routine chemistry. The 3′-substituted Cephem sulfone derivatives, evaluated as β-lactamase inhibitors by IC50 determinations, behave as weak inhibitors of the class D “oxacillinase” OXA1 from Escherichia coli and the class C β-lactamase of Enterobacter cloacae P99. Conversely, the 3′-unsubstituted Cephem sulfone 2 was shown to be comparable to sulbactam and even more active than clavulanic acid against the latter enzyme. The activity of 2 against E. cloacae P99 was also greatly enhanced by prolonging the pre-incubation time. Considerations as to the mechanism of inhibition are also put forward.
Ettore Perrone - One of the best experts on this subject based on the ideXlab platform.
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Tricyclic Cephems as inhibitors of human leukocyte elastase. Furo[3,4-c]cepham sulfones
Bioorganic & Medicinal Chemistry Letters, 1995Co-Authors: Marco Alpegiani, Pierluigi Bissolino, Riccardo Corigli, Vincenzo Rizzo, Ettore PerroneAbstract:Furo[3,4-c]cepham sulfones were efficiently obtained from 1,1-dioxo-3-methylCephem-4-ketones. Cyclization improved at one time stability of the β-lactam towards hydrolytic cleavage (pH 7.4) and reactivity (second-order inhibition rate constant kon) towards human leukocyte elastase.
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Cerium Ammonium Nitrate Promoted Alkoxylation of Cephem Sulfoxides and Sulfones
Synlett, 1994Co-Authors: Marco Alpegiani, Pierluigi Bissolino, Daniela Borghi, Ettore PerroneAbstract:At variance with their parent sulfides, Cephem-1s-sulfoxides are smoothly and steroselectively alkoxylated at C-4 upon reaction with cerium ammonium nitrate in the suitable alcohol. Moderate yields were obtained with Cephem sulfones.
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Functionalization of the dihydrothiazine ring of Cephem sulfones
HETEROCYCLES, 1993Co-Authors: Ettore Perrone, Marco Alpegiani, Pierluigi Bissolino, Daniela Borghi, Pietro Sbraletta, Roberto TonaniAbstract:Functionalization of the dihydrothiazine ring of Cephem esters and 4-ketones was studied at the sulfone oxidation level. On the esters, alkylation and Michael addition gave 4β- and 2α,4β-substituted products. On the ketones, electrophilic insertion of carbon, halo, oxygen and sulfur substituents was achieved with acceptable selectivity at 2α. Nucleophilic sulfenylation and acyloxylation was successful on 2-bromoCephem ketones, themselves electrophilic bromination products. Noticeable events included shift of the 3-Cephem double bond and epimerization at C-2. Configurations and ring conformation were evinced by nmr studies. Several compounds were potent inhibitors of human leukocyte elastase
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Synthesis of novel Cephem-4-ketones. A new series of human leukocyte elastase inhibitors
Tetrahedron Letters, 1991Co-Authors: Marco Alpegiani, Pierluigi Bissolino, Ettore Perrone, Giuseppe Cassinelli, Giovanni FranceschiAbstract:Alkylation of Cephem-4-carbonyl chlorides at the sulphide or sulphone oxidation level with Grignard reagents, stannanes and cuprates is described. Radical or ionic bromination of the 3-methylCephem-4-ketone 8, followed by displacement with heterocyclic thiols, provides an entry to 3′- and 2-thiosubstituted derivatives, which are new potent inhibitors of HLE. Alkylation of Cephem-4-carbonyl chlorides with Grignard reagents, stannanes or cuprates, prior or after oxidation, gave 3a≈f(X Cl; R But, Et, Ph.Bz.H; R′OAc). Similarly, 8 (X OMe, R But, R′ H) was prepared and converted to 13a≈c (R′ S-Het) and 14a≈c via radical and ionic bromination, respectively. The new Cephem-4-ketones are potent inhibitors of human leukocyte elastase.
Hiroshi Kumase - One of the best experts on this subject based on the ideXlab platform.
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Reductive cross-coupling of 3-substituted delta 3-Cephems with alkenyl halides in an Al/PbBr2/NiBr2(bpy) triplemetal redox system. Synthesis of 3-alkenyl-delta 3-Cephems.
The Journal of organic chemistry, 2001Co-Authors: Hideo Tanaka, Jinfeng Zhao, Hiroshi KumaseAbstract:Synthesis of 3-alkenyl-delta 3-Cephems was performed successfully by cross-coupling 3-(trifluoromethylsulfonyloxy or chloro)-delta 3-Cephem with alkenyl halides, e.g., vinyl bromide, trans-1-bromo-1-propene, and trans-beta-bromostyrene in an Al/cat.PbBr2/cat.NiBr2(bpy)/NMP (or DMF) system. Reduction of 3-(trifluoromethylsulfonyloxy)-delta 3-Cephem into norcephalosporin was also achieved by a similar reaction in the presence of 5 molar equiv of water. Scope and a plausible mechanism of the Al/Pb/Ni triplemetal-redox promoted reactions are discussed.
Marco Alpegiani - One of the best experts on this subject based on the ideXlab platform.
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Tricyclic Cephems as inhibitors of human leukocyte elastase. Furo[3,4-c]cepham sulfones
Bioorganic & Medicinal Chemistry Letters, 1995Co-Authors: Marco Alpegiani, Pierluigi Bissolino, Riccardo Corigli, Vincenzo Rizzo, Ettore PerroneAbstract:Furo[3,4-c]cepham sulfones were efficiently obtained from 1,1-dioxo-3-methylCephem-4-ketones. Cyclization improved at one time stability of the β-lactam towards hydrolytic cleavage (pH 7.4) and reactivity (second-order inhibition rate constant kon) towards human leukocyte elastase.
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Cerium Ammonium Nitrate Promoted Alkoxylation of Cephem Sulfoxides and Sulfones
Synlett, 1994Co-Authors: Marco Alpegiani, Pierluigi Bissolino, Daniela Borghi, Ettore PerroneAbstract:At variance with their parent sulfides, Cephem-1s-sulfoxides are smoothly and steroselectively alkoxylated at C-4 upon reaction with cerium ammonium nitrate in the suitable alcohol. Moderate yields were obtained with Cephem sulfones.
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Functionalization of the dihydrothiazine ring of Cephem sulfones
HETEROCYCLES, 1993Co-Authors: Ettore Perrone, Marco Alpegiani, Pierluigi Bissolino, Daniela Borghi, Pietro Sbraletta, Roberto TonaniAbstract:Functionalization of the dihydrothiazine ring of Cephem esters and 4-ketones was studied at the sulfone oxidation level. On the esters, alkylation and Michael addition gave 4β- and 2α,4β-substituted products. On the ketones, electrophilic insertion of carbon, halo, oxygen and sulfur substituents was achieved with acceptable selectivity at 2α. Nucleophilic sulfenylation and acyloxylation was successful on 2-bromoCephem ketones, themselves electrophilic bromination products. Noticeable events included shift of the 3-Cephem double bond and epimerization at C-2. Configurations and ring conformation were evinced by nmr studies. Several compounds were potent inhibitors of human leukocyte elastase
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Synthesis of novel Cephem-4-ketones. A new series of human leukocyte elastase inhibitors
Tetrahedron Letters, 1991Co-Authors: Marco Alpegiani, Pierluigi Bissolino, Ettore Perrone, Giuseppe Cassinelli, Giovanni FranceschiAbstract:Alkylation of Cephem-4-carbonyl chlorides at the sulphide or sulphone oxidation level with Grignard reagents, stannanes and cuprates is described. Radical or ionic bromination of the 3-methylCephem-4-ketone 8, followed by displacement with heterocyclic thiols, provides an entry to 3′- and 2-thiosubstituted derivatives, which are new potent inhibitors of HLE. Alkylation of Cephem-4-carbonyl chlorides with Grignard reagents, stannanes or cuprates, prior or after oxidation, gave 3a≈f(X Cl; R But, Et, Ph.Bz.H; R′OAc). Similarly, 8 (X OMe, R But, R′ H) was prepared and converted to 13a≈c (R′ S-Het) and 14a≈c via radical and ionic bromination, respectively. The new Cephem-4-ketones are potent inhibitors of human leukocyte elastase.