Asymmetric oxidation of sulfides

This review discusses synthesis of enantiopure sulfoxides through the asymmetric oxidation of prochiral sulfides. The use of metal complexes to promote asymmetric sulfoxidation is described in detail, with a particular emphasis on the synthesis of biologically active sulfoxides. The use of non-metal-based systems, such as oxaziridines, chiral hydroperoxides and peracids, as well as enzyme-catalyzed sulfoxidations is also examined.

Studies on the Catalytic Asymmetric Fischer Indolization

This work describes further developments and applications of the catalytic asymmetric Fischer indolization. In the first part of this thesis, the development of an organocatalytic asymmetric synthesis of helicenes via a Fischer indolization is discussed. The application of a novel SPINOL-derived phosphoric acid, featuring extended π-surfaces as 3,3‘-substituents which can potentially participate in π-interactions with the polyaromatic intermediate, afforded the corresponding products in high yields and enantioselectivities. The second part of this work describes the development of a catalytic asymmetric dearomatizing synthesis of 1,4-diketones via an interrupted Fischer indolization. Employing aryl hydrazines with α-substituents next to the hydrazine group prevents the rearomatization which takes place in common Fischer indole syntheses, thus enabling the hydrolysis of the generated diimine species. In the presence of STRIP as catalyst, a variety of different 1,4-diketones could be obtained in generally high yields, diastereo- and enantioselectivities. The last part of this thesis deals with the development of an organocatalytic asymmetric stereodivergent synthesis of novel 3H- and 2H-pyrroles, applying an interrupted Fischer indolization and for the 2H-pyrroles a subsequent stereospecific [1,5]-alkyl shift. Employing STRIP as catalyst afforded the corresponding products in good to excellent yields and enantioselectivities. Preliminary biological investigations of these novel structure motifs in cell-based assays, monitoring biological signal transduction pathways showed an inhibition of the Hedgehog signaling pathway in a μM range.

Catalytic Asymmetric Transfer Hydrogenation of Imines: Recent Advances

In this review article recent developments in the asymmetric transfer hydrogenation of imines from 2008 up to today are presented. The main methodology involves either metal-catalyzed procedures in the presence of a chiral ligand or organocatalyzed technologies using a Hantzsch ester and a chiral BINOL-derived phosphoric acid. The most important procedures are collected, paying special attention to the application of this methodology in synthetic organic chemistry.

Functionalization of (2S)-Isopropyl-5-iodo-2,3-dihydro-4(H)-pyrimidin-4-ones by a Suzuki-Miyaura Cross-Coupling Reaction Using Aryltrifluoroborate Salts: Convenient Enantioselective Preparation of alpha-Substituted beta-Amino Acids

A simple protocol for the Pd(OAc)(2)-catalyzed cross-coupling reaction of 1-benzoyl-(2S)-isopropyl-5-iodo-2,3-dihydro-4(H)-pyrimidin-4-ones with potassium aryltrifluoroborates was developed. The reaction is performed at 110 degrees C with a ligand-free catalyst. In all cases, complete conversion of the 1-benzoyl-(2S)-isopropyl-5-iodo-2,3-dihydro-4(H)-pyrimidin-4-ones and aryltrifluoroborates into the C-C coupling products was observed within 30-360 min. It is noteworthy that a large variety of groups present in the potassium aryltrifluoroborates (-CF(3), -OMe, -SEt, -CN, -CHO, -Cl, -Cbz, -NCbz, -OH, -CO(2)H) could be tolerated. Hydrogenation of the endocyclic double bonds in the Suzuki-Miyaura products followed by acid hydrolysis afforded highly enantioenriched alpha-aryl-substituted beta-amino acids.

Phoriospongin A and B: Two new nematocidal depsipeptides from the Australian marine sponges Phoriospongia sp and Callyspongia bilamellata

Bioassay-directed fractionation of two southern Australian sponges, Phoriospongia sp. and Callyspongia bilamellata, yielded two new nematocidal depsipeptides, identified as phoriospongins A (1) and B (2). The structures of the phoriospongins were determined by detailed spectroscopic analysis and comparison with the previously reported sponge depsipeptide cyclolithistide A (3), as well as ESIMS and HPLC analysis of acid hydrolysates. It is noteworthy that the unique and yet structurally related metabolites 1-3 are found in sponges spanning three taxonomic orders, Poescilosclerida, Haplosclerida, and Lithistida.

Projeto e construção de um bioreator para síntese orgânica assimétrica catalisada por saccharomyces cerevisiae (fermento biológico de padaria)

A model for the construction of a simple and cheap apparatus to be used as bioreactor for reactions catalyzed by baker's yeast (Saccharomyces cerevisiae) is described. The bioconversion and separation of cells from products and residual substrates are obtained at the same time. The reactions carried out in this type of reactor are faster than those catalyzed by immobilized cells. Yeast cells can be cultivated in this bioreactor operating with cell recycling at appropriated conditions using glucose and other nutrients.

Substâncias enantiomericamente puras (SEP): a questão dos fármacos quirais

The thalidomide disaster, in the 60,s, is the most painful reminder of the importance of chirality for biological activity. After this episode, much attention has been devoted to study the correlations between toxicological and pharmacological properties and chirality. Actualy, to get a licence for a new chiral drug in EUA, European community and Japan, it is necessary to study the biological properties of each enatiomer independently. This article presents an overview about the importance of the chirality of organic compounds and its relationships with biological activity, asymmetric synthetic methodologies and market.

Unsaturated Oxazolopiperidone Lactams: an Unexpected Domino-type Double Conjugate Additioncyclization Process

Reactions of 2-acetylindole enolate with unsaturated oxazolopiperidones 3, 4 and 10 unexpectedly gives pentacyclic dilactams 6, 7 and 11, respectively, resulting from a domino-type process involving two successive conjugate additions and a final cyclization.

Abordagens em síntese assimétrica

The approaches in asymmetric synthesis as the chiron approach, chiral auxiliaries, chiral reagents and asymmetric catalysis are described in a simplified way.

Catálise de transferência de fase

Since its discovery, phase transfer catalysis (PTC) has grown considerably and nowadays is one of the most versatile preparative methods. The search for new catalysts, their use in PTC asymmetric synthesis and the attempts to understand their mechanistic role are modern and exciting topics of investigation. A review on main achievements in the last two decades is presented.

Stereoselective syntheses of (+)- isoretronecanol and (+)-5-epi-tashiromine via addition of chiral titanium (iv) enolates to cyclic n-acyliminium ions

The stereoselective addition of the titanium (IV) enolates derived from (S)-4-isopropyl-N-4-chlorobutyryl-1,3-thiazolidine-2-thione (8) and from (S)-4-isopropyl-N-4-chloropentanoyl-1,3-thiazolidine-2-thione (9) to N-Boc-2-methoxypyrrolidine (5b) afforded the addition products (+)-10 and (+)-11 in 84% yield in both cases, as 8.6:1 and 10:1 diastereoisomeric mixtures, respectively. A three-step sequence allowed to convert these adducts to (+)-isoretronecanol (1) and (+)-5-epi-tashiromine (2) in 43% and 49% overall yield, respectively.

Síntese de aminoálcoois derivados do D-manitol

Aminoalcohols have found important applications in synthetic and medicinal chemistry, being used as chiral building blocks for the synthesis of many biologically active compounds. This class of compounds has been also used as chiral auxiliaries and ligands in asymmetric synthesis. Due to the importance of aminoalcohols in the treatment of several diseases, such as tuberculosis, the aim of this article is the synthesis and preliminary evaluation against tuberculosis of six aminoalcohols in 5 or 6 steps using D-mannitol as starting material, which is a useful carbohydrate employed in many syntheses.

Reações de organocatálise com aminas quirais: aspectos mecanísticos e aplicações em síntese orgânica

The philosophy of organocatalysis is based on the utilization of organic compounds to catalyze organic transformations without the intervention of metals. This area has attracted much attention of the synthetic chemistry community on the last years, which can be confirmed by the explosion of published papers dealing with this subject. Phosphorus compounds, urea and thiourea derivatives, alkaloids, guanidine derivatives, for example, have already been used as organocatalysts. In this review we have focused on the use of chiral amines as organocatalyst. We have also chosen some outstanding examples to demonstrate the potentiality of this strategy in the synthesis of natural products and biologically active compounds.

Potencialidades e oportunidades na química da sacarose e outros açúcares

Non-renewable biomass, such as coal, oil and natural gas are not only energy sources but also important starting materials for the production of a variety of chemicals ranging from gasoline, diesel oil and fine chemicals. In this regard, carbohydrates, the most abundant class of enantiopure organic compounds, are very suitable for generation of chemicals of great practical value. Their bulk-scale availability associated with low cost make them unique starting materials for organic preparative purpose. They are a most attractive alternative for construction of enantiopure target molecules by asymmetric synthesis. This review addresses, in addition to the use of low molecular weight carbohydrates, issues related to renewable biomass from photosynthesis and alternatives for the production of bulk and fine chemicals.

Development of racemization catalysts for dynamic kinetic resolution

Preparation of optically active compounds is of high importance in modern medicinal chemistry. Despite recent advances in the field of asymmetric synthesis, resolution of racemates still remains the most utilized way for preparation of single enantiomers in industrial scale due to its cost-efficiency and simplicity. Enzymatic kinetic resolution (KR) of racemates is a classical method for separation of enantiomers. One of its drawbacks is the limitation of target enantiomer yield to 50%. Dynamic Kinetic Resolution (DKR) allows to reach yields up to 100% by in situ racemization of the less reactive enantiomer. In the first part of this thesis, a number of half-sandwich ruthenium complexes were prepared and evaluated as catalysts for racemization of optically active secondary alcohols. A leading catalyst, Bn5CpRu(CO)2Cl, was identified. The catalyst discovered was extensively characterized by its application for DKR of a broad range of secondary alcohols in a wide range of reaction loadings (1 mmol – 1 mol). Cost-efficient chromatography-free procedure for preparation of this catalyst was developed. Further, detailed kinetic and mechanistic studies of the racemization reactions were performed. Comparison of racemization rates in the presence of Bn5CpRu(CO)2Cl and Ph5CpRu(CO)2Cl catalysts reveals that the performance of the catalytic system can be adjusted by matching of the electronic properties of the catalysts and the substrates. Moreover, dependence of the rate-limiting step from the electronic properties of the reagents was observed. Important conclusions about reaction mechanism were made. Finally, an alternative approach to DKR of amines based on space separated vessels was addressed. This procedure allows the combination of thermolabile enzyme with racemization catalysts active only at high temperatures.