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1.
J Org Chem ; 72(16): 5960-7, 2007 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-17616228

RESUMO

The Directed ortho Metalation (DoM)/Suzuki-Miyaura cross-coupling strategy is applied for the regiospecific construction of all isomeric monochloro and selected dichloro and trichloro 2,3-dihydroxybiphenyls (DHBs). The combined methodology highlights iterative DoM processes, hindered Suzuki-Miyaura couplings, and advantages in diversity in approaches from commercial starting materials leading to provision of chloro-DHBs as single isomers in high purity and on a gram scale. The syntheis of several PCBs are also reported.


Assuntos
Compostos de Bifenilo/síntese química , Catecóis/síntese química , Química Orgânica/métodos , Bifenilos Policlorados/síntese química , Indicadores e Reagentes , Espectroscopia de Ressonância Magnética , Modelos Químicos , Oxirredução , Estereoisomerismo
2.
Arch Pharm (Weinheim) ; 330(7): 211-4, 1997 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-9311300

RESUMO

The key step in the synthesis of the pharmacologically interesting 1-phenyltetrahydro-3-benzazepine skeleton is the Michael addition of (2-lithiophenyl)acetaldehyde acetals, which are generated in situ upon treatment of the bromo acetals 5a,b with n-butyllithium, to beta-nitrostyrene (6). The reductive ring closure of the nitro acetals 7a,b succeeded with zinc dust and hydrochloric acid to give the 3-benzazepines 11a,b in good yields. The unsubstituted 3-benzazepine 11a showed a considerable affinity for the phencyclidine binding site of the NMDA receptor (Ki = 6.41 microM), whereas donor substituents in the aryl moiety (11b,c) reduce the affinity for the NMDA receptor.


Assuntos
Benzazepinas/síntese química , Benzazepinas/farmacologia , N-Metilaspartato/antagonistas & inibidores , Ligação Competitiva , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Receptores de N-Metil-D-Aspartato/efeitos dos fármacos , Receptores de N-Metil-D-Aspartato/metabolismo , Relação Estrutura-Atividade
3.
J Biol Chem ; 275(21): 15701-8, 2000 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-10821847

RESUMO

The ability of 2-hydroxy-6-oxo-6-phenylhexa-2,4-dienoate (HOPDA) hydrolase (BphD) of Burkholderia cepacia LB400 to hydrolyze polychlorinated biphenyl (PCB) metabolites was assessed by determining its specificity for monochlorinated HOPDAs. The relative specificities of BphD for HOPDAs bearing chlorine substituents on the phenyl moiety were 0.28, 0.38, and 1.1 for 8-Cl, 9-Cl, and 10-Cl HOPDA, respectively, versus HOPDA (100 mm phosphate, pH 7.5, 25 degrees C). In contrast, HOPDAs bearing chlorine substituents on the dienoate moiety were poor substrates for BphD, which hydrolyzed 3-Cl, 4-Cl, and 5-Cl HOPDA at relative maximal rates of 2.1 x 10(-3), 1.4 x 10(-4), and 0.36, respectively, versus HOPDA. The enzymatic transformation of 3-, 5-, 8-, 9-, and 10-Cl HOPDAs yielded stoichiometric quantities of the corresponding benzoate, indicating that BphD catalyzes the hydrolysis of these HOPDAs in the same manner as unchlorinated HOPDA. HOPDAs also underwent a nonenzymatic transformation to products that included acetophenone. In the case of 4-Cl HOPDA, this transformation proceeded via the formation of 4-OH HOPDA (t(12) = 2.8 h; 100 mm phosphate, pH 7.5, 25 degrees C). 3-Cl HOPDA (t(12) = 504 h) was almost 3 times more stable than 4-OH HOPDA. Finally, 3-Cl, 4-Cl and 4-OH HOPDAs competitively inhibited the BphD-catalyzed hydrolysis of HOPDA (K(ic) values of 0.57 +/- 0. 04, 3.6 +/- 0.2, and 0.95 +/- 0.04 microm, respectively). These results explain the accumulation of HOPDAs and chloroacetophenones in the microbial degradation of certain PCB congeners. More significantly, they indicate that in the degradation of PCB mixtures, BphD would be inhibited, thereby slowing the mineralization of all congeners. BphD is thus a key determinant in the aerobic microbial degradation of PCBs.


Assuntos
Proteínas de Bactérias/metabolismo , Burkholderia cepacia/enzimologia , Hidrolases/metabolismo , Bifenilos Policlorados/metabolismo , Biodegradação Ambiental , Compostos Clorados/metabolismo , Ácidos Graxos Insaturados/metabolismo , Cinética , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Espectrofotometria , Especificidade por Substrato
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