Current Organic Synthesis - Volume 11, Issue 4, 2014

Development of efficient routes to many kinds of fused heterocycles is an attractive area of research since these compounds constitute one of the most interesting divisions of organic chemistry. A majority of the compounds produced by nature as well as significant numbers of compounds synthesized in the industrial sector each year have heterocyclic rings as part of their structures. This survey research works on the specific synthesis of oxazolo-, thiazolo-, pyrazolo- and imidazo-fused heterocycles by multi-component reactions over the last ten years. Different approaches for the synthesis of such systems are discussed.

Solid acid catalysts are the best alternative to existing homogeneous protic acids, being less toxic, easy to handle and most importantly having the additional possibility to be reused several times. In recent years, silica has been employed as porous support to immobilize a series of acid species towards the design of novel solid acid catalysts. These materials have been employed in several organic reactions, including alkylation, acylation, oxidation, protection reactions, hydrolysis, deprotection reactions, condensation and multicomponent reactions. The present work has been aimed to provide a short overview on relevant type of solid acids and their applications in heterogeneously catalyzed processes.

Tuberculosis (TB), mainly caused by Mycobacterium tuberculosis, is the leading killer among all infectious diseases worldwide and is responsible for more than two million deaths annually. The recent increase in the number of multi-drug resistant clinical isolates of M. tuberculosis has created an urgent need for the discovery and development of new antituberculosis leads. This review covers recent reports terpenoids that have demonstrated moderate to high activity in bioassays realized in vitro against M. tuberculosis; their organic synthesis is included in some cases. In this review, monoterpenoids, diterpenoids, sesquiterpenes, sesterterpenes and triterpenes, their structural analogs and semisynthetic derivatives will be discussed, with particular emphasis on the reported syntheses for each compound.

Microwave-Assisted Organic Synthesis (MAOS) is one of the most current trends in organic chemistry. Herein, both the most popular and new approaches in microwave-syntheses of very important linkage in Nature - amide bond - are overviewed and compared with conventional synthetic routes.

We prepared a series of bis-indole derivatives from different aldehydes and/or substituted isatins using molecular iodine as a catalyst and propylene carbonate as a “green” solvent. Simply stirring the components at room temperature produced high yield compound synthesis with a methodology that is clean, economical and efficient.

We describe the synthesis and characterization of three compounds targeting the enzyme 17β-hydroxysteroid dehydrogenase type 1. The first one is a 4-aminobenzoyl-phenylacetic acid derivative designed as a mimic of adenosine-phosphate, the second one is an estradiol derivative having a decyl side chain at position 16β, and the third one is a hybrid compound with the adenosine-phosphate mimic covalently linked to the C16-estradiol side chain. Judicious use of key reactions such as Claisen rearrangement, microwave Grignard alkylation, selective TEMPO oxidation and cross metathesis has been required to achieve these targeted molecules.

Buchwald-Hartwig coupling reaction was employed to furnish new class of substituted piperazine-fused thio-quinolinyl Schiff bases. Synthesis of thiocarbonyl quinoline moiety was attempted using Lawesson’s reagent followed by esterification achieved using ethyl bromoacetate in refluxing acetone. Substantial C-N coupling of various piperazine or piperidine bases to the C-6 position of quinoline ring system was accomplished using X-Phos as optimal ligand for the Pd(0)-catalyzed Buchwald-Hartwig amination. After the successful coupling in satisfactory yields, the ester derivatives were hydrazinolyzed using 99% hydrazine hydrate and the resulted analogs were reacted with thiophene-2-carbaldehye in refluxing ethanol using catalytic amount of acetic acid to access the intended class of Schiff bases. New products would be of significant interest for the biological applications verifying that Schiff bases are valuable biologically active components. The proposed structures of the new products were confirmed with the aid of spectroscopy techniques (FT-IR and 1H NMR) and elemental (CHN) analysis.