Reações de inserção intramolecular de diazo compostos polifuncionais catalisadas por ródio(II): síntese de oxetan-3-ona-2-carboxilato e outros heterociclos funcionalizados

gamma-Hydroxy-alpha-diazo-beta-ketoesters are key intermediates in the chemistry of penicilin-based antibiotics and natural products. The method developed here for the synthesis of ethyl 2-diazo-4-hydroxy-3-oxo-butanoate 17 (in two steps from the diazo mercurial 2) compares very favorably with those reported in the literature for similar compounds. The Rh2(OAc)4-mediated intramolecular OH-insertion reaction of the diazo hydroxy ester 17 was investigated, furnishing the oxetan-3-one-2-carboxilate 18 in good yield. When the diazo ester lacks a free hydroxyl group as in the case of the phenoxy diazo ester 11 an intramolecular CH-insertion takes place, affording the 2H-chromene 20 in almost quantitative yield. The behavior of other functionalized diazo esters towards Rh2(OAc)4 was also investigated.

Constituintes químicos das raízes de Pyrostegia Venusta e considerações sobre a sua importância medicinal

This paper describes the chemical constituents isolated from roots of Pyrostegia venusta. From ethanol extract of the roots allantoin, beta-sitosterol, 3b-O-beta-D-glupyranosylsitosterol and hesperedin were isolated. The structures of these natural products were identified on the basis of spectral data, including 2D NMR of the peracetyl derivative of hesperidin.

Wilhelm Michler, uma aventura científica nos trópicos

Wilhelm Michler lived in Brazil for seven years from 1882 to 1889, when he died. Here, he published several articles on natural products, and became a professor of Industrial Chemistry at the Escola Politécnica, in Rio de Janeiro. He was respected by colleagues and students. This article addresses this poorly known period of the life of a scientist, world-famous by the aromatic ketone that carries his name.

Produtos naturais das esponjas marinhas Aaptos sp., Hymeniacidon aff. heliophila, e do nudibrânquio Doris aff. verrucosa

Herein we describe the isolation of homarine and piridiniumbetaine B from the sponge Aaptos sp. Although homarine has a common occurrence among animals, piridiniumbetaine B was only recently isolated from the marine sponge Agelas dispar. The isolation of piridiniumbetaine B from two taxonomically distant marine sponges corroborate previous assumptions that such betaines should be regarded rather as primary metabolites. We have also isolated (9-[5'-(methylthio)-beta-D-xylofuranosyl]adenine (xylosyl-MTA) from the mantle of a nudibranch identified as Doris aff. verrucosa. The occurrence of xylosyl-MTA in the mantle of this animal strongly suggests that it is the same nudibranch species described for the Mediterranean sea. We have been unable to detect any other compound in the mantle extract of D. aff. verrucosa other than xylosil-MTA and sterols. GC-MS analysis of the sterol fraction from the nudibranch and its prey, the sponge Hymeniacidon aff. heliophila, revealed the occurrence of the ubiquitous sterols, cholesterol, brassicasterol, cholestanol, 24-methylcholesterol and 24-ethylcholesterol, as the only common metabolites, therefore precluding any assumption concerning the sequestration of secondary metabolites by the nudibranch from H. aff. heliophila.

Planejamento racional de fármacos baseado em produtos naturais

In the area of drug discovery, natural products represent a myriad of templates for new lead discovery. It is, however, most unlikely that the bioactive principle itself shall become a drug; it is much more likely that a medicinal chemistry project needs to be initiated as soon the potency or selectivity or specificity of the new natural product candidate has been disclosed. Brazil has an enormous biodiversity where just a few has been disclosed. Nevertheless, it urges to initiate a joint collaboration in order to circumvent a major breakdown linking between natural products and medicinal chemistry in this country. This paper is intended to encourage people to follow up one of the most pushing forward enterprise that needs to be settled: the pharmaceutical industry.

Constituintes químicos isolados de simira glaziovii (K. schum) steyerm. e a atribuição dos deslocamentos químicos dos átomos de carbono e hidrogênio do alcalóide ofiorina e seus derivados

Chromatographic fractionation of bark extracts from Simira glaziovii (Rubiaceae) afforded the steroids beta-sitostenone, stigmastenone, beta-sitosterol and stigmasterol, methyl trans-4-hidroxy-3-methoxycinamate (1), the alkaloids harmane (2) and the new stereoisomer of ophiorine B (3). The structures were established by ¹H and 13C NMR, including 2D techniques and mass spectral analysis, of the natural products and pentaacetyllyalosidic acid (4a) and beta-carboline monoterpene tetraacetylglucoside (5, 1,22-lactamlyaloside) derivatives obtained by chemical transformations.

Estratégia de simplificação molecular no planejamento racional de fármacos: a descoberta de novo agente cardioativo

In this article are described examples of the successful use of molecular simplification strategy in the discovery of new drugs from bioactive natural products and synthetic compounds. The discovery of a new cardiotonic derivative (37, 2-thienylidene-3,4-methylenedioxybenzoylhydrazine; LASSBio-294), efficiently synthesized from Brazilian natural product and structurally designed by molecular simplification of active pyridazinone compounds reported in the literature, is described. A brief description of the pharmacological profile of this new cardiotonic lead-compound, belonging to the N-acylhydrazone (NAH) class, is also reported herein.

Produtos naturais: atualidade, desafios e perspectivas

This article offers an overview on the historical facts and the recent state of art of Chemistry of Natural Products which, in the course of 25 years of SBQ, have led to the present development of this area in Brazil. In addition, this article deals with the last trends on Natural Products in Brazil and also in developed countries.

Álcoois quirais: métodos químicos e catalíticos de obtenção por redução assimétrica

The importance of chiral alcohols as starting materials for the production of fine chemicals and as useful chirons for the building of several interesting molecules or natural products is reported. The useful and common methods of asymmetric reduction such as the chemical (with organoboron or organoaluminum reagents) and the catalytic ones (with ruthenium or rhodium complexes) for preparation of chiral alcohols are described; even the newer and much more rare electrocatalytic methods are reported.

Seleção de plantas com atividade anticolinasterase para tratamento da doença de Alzheimer

Alzheimer's disease (AD) is a neurodegenerative disease characterized by cognite impairment and personality changes. The development of drugs for the treatment of the cognitive deficits of AD has focused on agents which counteract loss in cholinergic activities. These symptons of AD have been successfully treated with acetylcholinesterase (AchE) inhibitors (eg. galanthamine). There still is great interest in finding better AchE inhibitors. We use Ellmann's microplate assay and silica gel thin-layer chromatography (TLC) to screen natural products from plants as new sources of AchE inhibitors.

Terpenos com atividade inseticida: uma alternativa para o controle químico de insetos

Many substances from different sources have been used by men for decades to control insects. After the 2nd World War, the use of inorganic compounds have declined drastically and natural products, as well as synthetic derivatives, have been widely used instead. The search for natural alternatives have improved the development of bench top bioassays and an array of synthetic approaches for known and novel natural products that shows relevant activities as feeding supressors and deterrents. The studies concerning mode of action and environmental impact of these substances, that may be biodegradable and selective for undesired insects, had led to the evaluation and discovery of a number of molecules, mostly terpenoids and alkaloids, that are well reported as candidates for inseticidal compounds that could be an effective alternative for insects control with a lower impact on human health, household animals and the environment.

Reações aldólicas assimétricas catalíticas

This review describes the use of catalytic asymmetric aldol reactions of silyl enol ethers and silyl (thio)ketene acetals with aldehydes (the Mukaiyama aldol reaction) in order to illustrate its synthetic utility. A variety of Lewis acid and basic reagents were employed for catalytic aldol reactions with high diastereo- and enantioselectivities. The origins of the selectivity of these reactions are discussed and some representative examples of their application in the synthesis of natural products are presented. New developments in chiral heterobimettalic lanthanoid catalysis and enantioselective aldol reactions in aqueous media are also included.

Um olhar holístico sobre a química de produtos naturais brasileira

This paper describes a comparative analysis on natural product chemistry between the Brazilian Chemical Society journals and twelve representative international publications in the area. The search using the ISI Web of Knowledge disclosed 41,362 publications in the years 2000-2002 containing at least one researcher from a Brazilian Institution, from which 12% belongs to natural products.

Novos produtos naturais capazes de atuar na estabilização de microtúbulos, um importante alvo no combate ao câncer

Microtubules are involved in many aspects of cellular biology and represent an important target of anticancer chemotherapeutics. In the past five years, novel natural products such as epothilones, discodermolide, sarcodictyin, eleutherobin, and laulimalide, all of which have biological activities similar to those of paclitaxel (Taxolâ), have been discovered. Taxolâ is an important antitumor drug approved by the FDA for the treatment of ovarian, breast and non-small-cell lung carcinomas and became the first natural product described that stabilized microtubules avoiding the cellular replication. The present article reports new natural products that are able to act on the stabilization of microtubules.

Produtos naturais como candidatos a fármacos úteis no tratamento do Mal de Alzheimer

Alzheimer's disease (AD) is a progressive neurodegenerative pathology with severe economic and social impact. There is currently no cure, although cholinesterase inhibitors provide effective temporary relief of symptoms in some patients. Nowadays drug research and development are based on the cholinergic hypothesis that supports the cognition improvement by regulation of the synthesis and release of acetylcholine in the brain. There are only four commercial medicines approved for treatment of AD and natural products have played an important role in the research for new acetylcholinesterase inhibitors.