Beiträge zur Totalsynthese von Epothilon A und Derivaten

Natural product, epothilone, total synthesis, olefin metathesis, aldol reaction

Studien zur Totalsynthese der Sorangicine

Total synthesis, natural product, sorangicin, antibiotic, macrolide, carbo-Ferrier rearrangement

Arylfurans as potential Trypanosoma cruzi trypanothione reductase inhibitors

The natural lignans veraguensin and grandisin have been reported to be active against Trypanosoma cruzi bloodstream forms. Aiming at the total synthesis of these and related compounds, we prepared three 2-arylfurans and eight 2,5-diarylfurans. They were evaluated for their potential as T. cruzi trypanothione reductase (TR) inhibitors as well against the parasite's intracellular (amastigote) and bloodstream (trypomastigote) forms. Compound 12 was the most effective against TR with an IC50 of 48.5 µM while 7 and 14 were active against amastigotes, inhibiting the parasite development by 60% at 20 µg/ml (59 and 90 µM, respectively). On the other hand, none of the compounds was significantly active against the parasite bloodstream forms even at 250 µg/ml (0.6-1.5 mM).

Progress on Lamellarins

This review covers recent literature on the lamellarins, a family of marine natural products, and related analogs, encompassing synthetic strategies for total synthesis, structure-activity relationships (SAR), and studies on mechanisms of biological action, namely in the context of antitumor activity. It reviews work published from January 2008 to December 2010.

Utilização de α,α-Diclorociclobutanonas em Síntese de Produtos Naturais

The preparation and chemical potentiality of a,a-dichlorocyclobutanones as useful intermediates in the total synthesis of natural products are reviewed. Some aspects related to the recent advances reported in the literature about the mechanism of [2+2] cycloaddition reaction between dichloroketene and olefins are also presented.

Ambergris: perfume e síntese

Rules for the occurence of the ambergris odor is presented and discussed in terms of the relationship between chemical structure and odor. A general overview of the major approaches in the synthesis of Ambrox® , the key ambergris-type compound, is also presented.

Synthetic approaches towards the Lycopodium alkaloids

The Lycopodium alkaloids are a structurally diverse group of natural products isolated from Lycopodium with important biological effects for the potential treatment of cancer and severe neurodegenerative diseases. To date, full biological studies have been hampered by lack of material from natural sources. Total synthesis represents a possible solution to meet this demand as well as the most effective way to design new compounds to determine structural activity relationships and obtain more potent compounds. The aim of this chapter is to summarise the work carried out in this field so far by presenting an overview of the synthetic strategies used to access each of the four key Lycopodium alkaloid types. Particular emphasis has been placed on methods that rapidly construct each nucleus utilizing tandem reactions.

Synthetic approaches towards the Lycopodium alkaloids

The Lycopodium alkaloids are a structurally diverse group of natural products isolated from Lycopodium with important biological effects for the potential treatment of cancer and severe neurodegenerative diseases. To date, full biological studies have been hampered by lack of material from natural sources. Total synthesis represents a possible solution to meet this demand as well as the most effective way to design new compounds to determine structural activity relationships and obtain more potent compounds. The aim of this chapter is to summarise the work carried out in this field so far by presenting an overview of the synthetic strategies used to access each of the four key Lycopodium alkaloid types. Particular emphasis has been placed on methods that rapidly construct each nucleus utilizing tandem reactions.

A reação de metátese de olefinas: reorganização e ciclização de compostos orgânicos

The olefin metathesis reaction allows the exchange of complex alkyl units between two olefins, with the formation of a new olefinic link and a sub-product olefin usually ethylene. This reaction has found extensive application in the last ten years with the development of the Grubbs and Schrock catalysts, in total synthesis of complex organic molecules, as opposed to the very important use in the petrochemical industry with relatively simple molecules. This review intends to trace a historical and mechanistic pathway from industry to academy, before illustrating the more recent advances.

Síntese de sulfadiazina e sulfadiazina de prata em escala semi-micro: prática experimental em síntese de fármacos

The total synthesis of sulfadiazine and silver sulfadiazine from readily available starting materials was adapted to semi-micro laboratory scale and is proposed as an experiment in drug synthesis for undergraduate courses.

Indução assimétrica 1,5-Anti na adição de enolatos de boro de metilcetonas beta-oxigenadas a aldeídos

High levels of substrate-based 1,5-stereoinduction are obtained in the boron-mediated aldol reactions of beta-oxygenated methyl ketones with achiral and chiral aldehydes. Remote induction from the boron enolates gives the 1,5-anti adducts, with the enolate pi-facial selectivity critically dependent upon the nature of the beta-alkoxy protecting group. This 1,5-anti aldol methodology has been strategically employed in the total synthesis of several natural products. At present, the origin of the high level of 1,5-anti induction obtained with the boron enolates is unclear, although a model based on a hydrogen bonding between the alkoxy oxygen and the formyl hydrogen has been recently proposed.

A síntese dos sesquiterpenos baquenolidas

The bakkenolide group of sesquiterpenes has been a focal point of synthetic efforts amongst several research laboratories all linked to our common origins at the Chemistry Institute at the State University in São Paulo. In this review we would like to present a historical perspective of this research, with unpublished background information, and a definitive retrosynthetic analysis of these molecules. This chemistry spans the time period from 1972 to 2006, and traces the initial steps with Prof. Dr. Helena Ferraz to the present day.

Utilização do D-manitol em síntese orgânica

D-mannitol is used in several fields including food, pharmaceuticals, cosmetics and textiles being an important carbohydrate found widespread in nature. Due to its chirality, it is largely used in organic synthesis with several applications, such as ligands, polymers, chiral pool, for preparation of small chiral building blocks, key intermediates in total synthesis. In this context, the aim of this review is to highlights recent applications of D-mannitol, especially in total synthesis.

The syntheses of the marine metabolites 3-bromoverongiaquinol and 5-monobromocavernicolin

An efficient synthesis of the marine metabolite 3-bromoverongiaquinol (1) and the first total synthesis of 5-monobromocavernicolin (2), both isolated from the marine sponge Aplysina cavernicola, have been described based on the 1,2 addition of the lithium enolate of N,O-bistrimethylsilylacetamide (BSA, 4) to 1,4-benzoquinone (3). Bromination and purification of the crude product on silica gel chromatography provided 3-bromoverongiaquinol (1) in 50% overall yield. Under alkaline conditions, the crude product of the bromination reaction was converted to 5-monobromocavernicolin (2) in 20% yield which was also obtained in 13% yield (25% yield based on recovered starting material) from 3-bromoverongiaquinol (1).

Síntese da fenitoína assistida por micro-ondas: proposta de aula prática para alunos de graduação

Microwave synthesis is considered a breakthrough in the field of chemistry due to its benefits over conventional heating methods. We describe, for the first time, the total synthesis of phenytoin adapted for a microwave reactor, proposed as an experiment for undergraduate courses. When carried out with microwaves, the synthetic route provided phenytoin in 6 min and 30 s, while for conventional heating the total time was 170 min. The experiment also involves rapid identification of compounds by TLC, ¹H NMR, FT-IR and melting points determination.