Current Organic Synthesis - Volume 12, Issue 6, 2015

Environmental concerns associated with synthetic organic chemistry have posed stringent and compelling demands for greener processes. The development of cost-efficient and environmentally benign catalytic systems has become one of the main subjects in modern chemistry. In many chemical processes, organic solvents are widely used and had been a cause of major environmental concern due to their hazards. A recent benchmarking study performed by the pharmaceutical industry unveiled that solvents are the foremost contributor to the amount of waste produced in their manufacturing processes - the so-called E-Factor. Therefore, the scientific community has made an effort in order to develop alternative reaction media in place of volatile, pyrophoric, often toxic and of difficult recover solvents. This review provides an overview of the application of several alternative solvents derived from renewable feedstock in metal, organo- and biocatalysis. In addition, advantages and limitations of these solvents are also discussed.

In recent decades the need for new chiral compounds with high enantiomeric excesses has been rapidly emerging. Among the various methods used to achieve chiral compounds, one can highlight the enzymatic kinetic resolution of racemic esters, alcohols and amines and as the most versatile enzymatic methodology used in organic routes. Enzymes are used in biocatalytic routes to obtain enriched and enantiomerically pure compounds. The most remarkable biocatalysts for these processes are lipases, which have the capability of being used in organic media. Thus, the main purpose of this article was to present a review about studies conducted in Brazil involving the kinetic resolution of racemic compounds using lipases, also including unusual substrates containing heteroatoms, such as boron, silicon, selenium, tellurium and sulfur.

In recent years, the pharmacological potential of quinoxalines has received vast interest due to its many applications. This review centers on a critical overview of chemical diversity and physicochemical properties of bioactive quinoxaline libraries. In addition, recent strategies for obtaining structurally diverse quinoxalines using highly selective processes will be discussed.

Cryptococcosis, an invasive fungal infection that affects both immunocompromised and immunocompetent individuals, has emerged as an important public health problem in Africa, Asia, and America. The limited number of antimycotic drugs available to treat this disease, their side effects and toxicity, and the emergence of resistant strains support the search for more effective and less toxic compounds. This review compiles examples of novel synthetic compounds, which could be used as templates for developing novel drugs for the treatment of Cryptococcus infections.

Butenolides, five membered α,β-unsaturated γ-lactones, are ubiquitous moieties present in the structures of many natural products and synthetic compounds endowed with a large array of biological activities. Butenolides with an γ-alkylidene moiety are termed as γ-alkylidenebutenolides. Because of their chemical structures as well as their biological activities, butenolides have attracted the attention of synthetic organic chemistry community. As a consequence, several methodologies have been developed to synthesize these classes of compounds. The potential use of such substances is expanded due to their easy conversion into lactams and pyridazine derivatives which are also of potential biological interest. Moreover, the chemistry of such compounds is very rich in large extension associated also with the nature of their substituents. Herein, we present some classical and recent methodologies for the synthesis of butenolides and γ-alkylidene butenolides. These methods involve the use of several transition metal reagents, condensation and conjugated addition reactions. Some methods used to convert butenolides and γ-alkylidene congeners into lactams and pyridazines are described. Methodologies for the preparation of oxazolones namely azlactones, compounds which are structurally similar to butenolides and have attracted the attention of synthetic organic chemists due to their versatility as building blocks, are also highlighted. Examples of applications of the methodologies in the synthesis of natural products as well as in the preparation of analogues endowed with biological activities, including some contributions from the author’s groups, are discussed.

Isoflavonoids constitute an important class of natural products, comprising great structural diversity. Known as phytoalexins and phytoestrogens, these compounds exhibit interesting biological activities. The corresponding carba-analogues, in which the oxygen atom at the B-ring is replaced by a methylene, are emerging as an attractive alternative for the preparation of new bioactive compounds. In this review, we report our results on the synthesis of isoflavonoid analogues (5-carba-pterocarpans, 1-carba-isoflavanones, 5-carba-11-aza-pterocarpan and pterocarpanquinones) with anti-cancer, antiparasitic and anti-viral properties. Palladium-catalyzed oxyarylation and azaarylation of dihydronaphthalenes and α-arylation of α- tetralones were the key steps in the developed synthetic approaches. A historical background, as well as a brief mechanistic discussion of these reactions, will be presented.

The Claisen rearrangement, an important C–C bond forming reaction, has been used enormously for many decades in the synthesis of important class of compounds. This review covers developments in this rearrangement since 2008, discusses important aspects about the asymmetric Claisen rearrangement catalyzed by chiral organometallic Lewis acids or organic Brønsted-Lowry acids.

Liquid crystals are fascinating materials in many areas of applied science. They are widely known for their application in display technology and uses in other fields have also recently been identified, such as anisotropic networks, organic light-emitting diodes and photo- and semiconducting materials. Further applications in new areas continue to be developed, as well as effective solutions to problems associated with the limitations of liquid crystals. Designing novel thermotropic liquid crystals for applications in advanced functional materials involves the selection of a suitable central core, linking group and terminal functionality. Over the years, a very large number of heterocyclic compounds containing liquid crystal units have been synthesized. Interest in this field of research has increased considerably in recent years due to improvements in synthetic methodologies. This critical mini-review describes some basic design principles and synthetic approaches to prepare the most commonly found liquid crystals, especially fivemembered nitrogen heterocycles, such as 1,2,4- and 1,3,4-oxadiazols, isoxazole, 1,2,3-triazole, 1,3,4-thiadiazole, 1,3-thiazole and 2,1,3- benzothiadiazole.

We describe here a simple protocol for the synthesis of 4-(arylsulfenyl)-1H-pyrazoles by copper-catalyzed cyclocondensation and direct C–H bond sulfenylation reactions. The products were obtained in good yields by the reaction of a range of 1,3-diketones, arylhydrazines and arylthiols, using catalytic amount of CuI. This One-Pot Multicomponent protocol is an efficient method to synthesize new compounds with potential application in biological studies and material sciences.

The Morita-Baylis-Hillman reaction is an organocatalyzed chemical transformation that allows access to small poly-functionalized molecules and has considerable synthetic potential and promising biological profiles. In this review, we report the efforts made by Brazilian research groups in recent years on the development of Morita-Baylis-Hillman chemistry. The review covers these contributions, with a focus on mechanistic studies, improvement of the experimental conditions, and the use of Morita-Baylis-Hillman adducts as building blocks for the synthesis of heterocycles, natural products and drugs.