ABSTRACT
A diastereoselective route to (+)-bakkenolide A is presented from the readily available optically active Wieland-Miescher ketone. This novel synthesis of this sesquiterpene lactone features the following as key stereoselective transformations: (i) the ring contraction reaction of a octalone mediated by thallium(III) nitrate (TTN); (ii) a hydrogenation to create the cis-fused junction; and (iii) the formation of the C7 quaternary center through an enolate intermediate. Furthermore, during this work, the absolute configuration of a trinorsesquiterpene isolated from Senecio humillimus was assigned.
Subject(s)
4-Butyrolactone/analogs & derivatives , Antineoplastic Agents/chemical synthesis , Insecticides/chemical synthesis , 4-Butyrolactone/chemical synthesis , Hydrogenation , Ketones/chemistry , Molecular Conformation , Molecular Structure , Senecio/chemistry , Sesquiterpenes/isolation & purification , Spiro Compounds/chemistry , Stereoisomerism , Thallium/chemistryABSTRACT
The first synthesis of the natural product (+)-mutisianthol was accomplished in 11 steps and in 21% overall yield from 2-methylanisole. The synthesis of its enantiomer was also performed in a similar overall yield. The absolute configuration of the sesquiterpene (+)-mutisianthol was assigned as (1S,3R). Key steps in the route are the asymmetric hydrogenation of a nonfunctionalized olefin using chiral iridium catalysts and the ring contraction of 1,2-dihydronaphthalenes using thallium(III) or iodine(III). The target molecules show moderate activity against the human tumor cell lines SF-295, HCT-8, and MDA-MB-435.
Subject(s)
Anisoles/chemistry , Antineoplastic Agents/chemical synthesis , Biological Products/chemical synthesis , Sesquiterpenes/chemical synthesis , Alkenes/chemistry , Antineoplastic Agents/pharmacology , Biological Products/pharmacology , Cell Line, Tumor , Drug Screening Assays, Antitumor , Humans , Hydrogenation , Sesquiterpenes/chemistry , Sesquiterpenes/pharmacology , StereoisomerismABSTRACT
The reaction of a series of cis-fused bicyclic beta-hydroxytetrahydrofurans with ruthenium tetraoxide, generated in situ from ruthenium trichloride and sodium periodate, afforded 9- and 10-membered keto-lactones in moderate to good yields, in a clean and straightforward fashion. The starting beta-hydroxyethers were obtained from the corresponding 3-alkenols by two alternative procedures, depending on their pattern of substitution: (a) epoxidation by dimethyldioxirane, followed by base-catalyzed cyclization of the resulting epoxyalcohol, and (b) thallium trinitrate-mediated cyclization of the 3-alkenols, a method already described by our group.
Subject(s)
Bridged Bicyclo Compounds/chemistry , Furans/chemistry , Lactones/chemical synthesis , Catalysis , Crystallography, X-Ray , Lactones/chemistry , Molecular Structure , StereoisomerismABSTRACT
From previous results with lower homologues, dehydroiodination of the three alkenyl-beta-enamino esters 3a-c was expected to provide six-membered N-heterocyclic products. The reactions of 3a-c with triethylamine are found to lead, however, to the unexpected stereoselective synthesis of the trisubstituted cyclopentane derivatives 4a-c, as confirmed by IR and NMR spectroscopy. Cyclopentanes 4a-c bear two chiral centers and a gamma-amino ester moiety, and are therefore conformationally restricted analogues of gamma-amino butyric acid (GABA), which is the major inhibitory neurotransmitter in the central nervous system. Use of electrospray ionization mass (ESI-MS) and tandem mass spectrometry (ESI-MS/MS) allowed the key iminium ion intermediates 5a-c(+), as well as the protonated molecules of both the reactant and final products, [3a-c + H](+) and [4a-c + H](+), to be intercepted and structurally characterized. From these findings a mechanism for this unexpected but synthetically attractive and efficient stereoselective reaction is proposed.
Subject(s)
Cyclopentanes/chemical synthesis , Spectrometry, Mass, Electrospray Ionization/methods , gamma-Aminobutyric Acid/analogs & derivatives , gamma-Aminobutyric Acid/chemical synthesis , Combinatorial Chemistry Techniques , Molecular Structure , Stereoisomerism , gamma-Aminobutyric Acid/chemistryABSTRACT
[reaction: see text] A new use of ruthenium tetraoxide is reported. The catalytic oxidative cleavage of hexahydro-benzofuran-3a-ols led to nine-membered ring keto-lactones in moderate to good yields and high purity. The reaction is clean and easily performed using catalytic amounts of ruthenium trichloride and an excess of sodium periodate as a cooxidant.
ABSTRACT
In this work we describe the cyclofunctionalization of eleven differently substituted alkenyl-beta-dicarbonyl compounds, employing three electrophilic reagents, namely, iodine, p-methoxyphenyltellurium trichloride, and phenylselenenyl bromide. The reactions occur through the enolic form of the substrates, to afford the corresponding iodo-, telluro-, or selenocyclic enol ethers. Substrates bearing trisubstituted double bonds failed in reacting with the selenium and tellurium reagents. In general, beta-diketones reacted faster than beta-keto esters with the three studied electrophiles.
ABSTRACT
The reaction of a series of six-membered ring 3-alkenols with thallium trinitrate (TTN) in three different experimental conditions was studied. Either cyclization products or ring contraction products were obtained, depending on the structure of the substrate as well as the nature of the solvent. The reaction of a seven-membered ring 3-alkenol with TTN led to the ring contraction product exclusively.
ABSTRACT
Neste trabalho apresenta-se a concepçäo Psicomotora do desenvovimento infantil abordando suscintamente os seus fundamentos teóricos. Em seguida analisa-se a síndrome do autismo, suas controvérsias teóricas e as dificuldades conceituais. A autora caracteriza o autismo em termos de uma dificuldade peculiar de comunicaçäo ser-mundo e, nesta perspectiva, coloca a importância da psicomotricidade na compreensäo de alguns aspectos gerais do desenvolvimento psicológico da criança e, em particular, do autismo infantil. Finalizando, conclui-se sobre a contribuiçäo desta abordagem na psicoterapia da criança autista como meio de reorganizar sua auto-imagem e definir sua identidade, condiçäo essencial ao seu desenvolvimento Psicomotor
Subject(s)
Autistic DisorderABSTRACT
Neste trabalho apresenta-se a concepcao Psicomotora do desenvolvimento infantil abordando suscintamente os seus fundamentos teoricos. Em seguida analisa-se a sindrome do autismo, suas controversias teoricas e as dificuldades conceituais. A autora caracteriza o autismo em termos de uma dificuldade peculiar de comunicacao ser-mundo e, nesta perspectiva, coloca a importancia da psicomotricidade na compreensao de alguns aspectos gerais do desenvolvimento psicologico da crianca e, em particular, do autismo infantil. Finalizando, conclui-se sobre a contribuicao desta abordagem na psicoterapia da crianca autista como meio de reorganizar sua auto-imagem e definir sua identidade, condicao essencial ao seu desenvolvimento Psicomotor.
Subject(s)
Autistic Disorder , Child Development , Autistic Disorder , Self ConceptABSTRACT
Säo apresentados 12 casos de crianças com a síndrome de imunodeficiência adquirida (AIDS), atendidos no Instituto da Criança "Prof. Pedro de Alcantara", no período de 1985/1986. As principais características clínicas encontradas foram linfoadenioopatia, dificuldade de ganho de peso, anorexia, hepatomegalia, esplenomegalia, assim como infecçöes causadas por germes oportunistas. Entre os achado laboratoriais destacam-se a inversäo T4/T8 e a hipergamaglobulinemia. Como meio da contaminaçäo foram detectados: uso rotineiro de derivados de sangue em cinco crianças, exsangüíneo-transfusäo em uma, transfusäo única de derivados de sangue em três, transmissäo vertical em dois e transmissäo näo bem esclarecida em um paciente. Neste artigo säo ainda discutidos os critérios para diagnóstico da síndrome no grupo pediátrico
Subject(s)
Child, Preschool , Child , Humans , Male , Female , Acquired Immunodeficiency Syndrome/diagnosis , Enzyme-Linked Immunosorbent Assay , Fluorescent Antibody Technique , HIV/analysisABSTRACT
Apresenta-se a experiência do Instituto da Criança "Prof. Pedro de Alcantara" do Hospital das Cínicas da Faculdade de Medicina da Universidade de Säo Paulo em relaçäo às imunodeficiências primárias. Säo apresentados 57 pacientes diagnosticados entre 1978 e 1985. O maior contingente foi de imunodeficiência humoral (64,9%) seguido pelos distúrbios ligados aos neutrófilos. A avaliaçäo laboratorial foi feita através de um "screening" com a finalidade de obter o maior número de dados através do menor número de exames. Houve seis óbitos