Current Organic Chemistry - Volume 8, Issue 4, 2004

Epothilones exhibit high antitumor activities with the same mechanism of action as Taxol and retain a much greater toxicity against p-glycoprotein overexpressing multiple drug resistant (MDR) cells. The realization of their unique potential as antitumor agents resulted in an intense race for their total synthesis, structure modification, and biological investigation. Recently a wealth of new chemistry has been developed in the synthesis of epothilone family. This review will present recent progress in the syntheses of epothilones and analogues.

The solid phase peptide synthesis is based on repetitive cycles (deprotection and coupling) that cannot be monitored with the analytical methods used in organic chemistry because of the presence of the solid support. Various methods have been developed for monitoring the synthetic steps, which can be qualitative and / or quantitative destructive or non-destructive. The irreversible or destructive analytical methods are carried out on aliquots of the peptide-resin and a lot of these are based on the presence of the free amino group. The non-destructive methods can be carried out on the total batch; many of these derive from the modification of the techniques used in organic chemistry such as UV, IR and NMR. If the peptide is cleaved from the resin, it is possible to utilize the conventional analytical methods used for organic chemistry. Every detection method differs in terms of sensitivity, applicability, rapidity and almost all cannot be applied in the automated instrumentations.

Renewed interest in the chemistry of polycyclic aromatic hydrocarbons (PAHs) has been stimulated by recent research advances in several areas. Prominent among these are: the discovery of buckminsterfullerene and related molecules; elucidation of the mechanisms of carcinogenesis of PAHs some of which are widespread contaminants in the human environment; and syntheses of large PAH ring systems that have interesting structural and electronic properties. These advances have fostered development of milder, more efficient methods for the synthesis of PAHs to replace older established methods that require drastic conditions and often afford relatively poor yields. This review provides an overview of methods for the synthesis of PAHs with emphasis on newer synthetic approaches. The latter include thermolysis and flash vacuum pyrolysis, inter- and intramolecular metal-catalyzed cross coupling reactions, such as Suzuki coupling, alkylation of activated forms of carbonyl compounds, such as enamines and silyl enol ethers, and cyclotrimerization of arynes and acetylenes. Recent advances and improvements in some of the established methods, such as oxidative photocyclization, Diels-Alder cycloaddition, and the Wittig reaction, are also covered.

Heterocyclic enamines are versatile intermediates for the synthesis of heterocyclic compounds and natural products, which are not readily obtainable by other synthetic means. One of the most intriguing features of heterocyclic enamines is their ambident bisnucleophilicity; nucleophilic reaction can take place at the site of enaminic carbon and / or the secondary amino nitrogen. These unique reaction properties lead to intriguing regioselectivity in the reaction with monoelectrophiles and biselectrophiles to produce different types of heterocyclic compounds. In this article, we will briefly introduce the methods of preparing secondary and tertiary heterocyclic enamines and then review the selective reactions of secondary heterocyclic enamines with emphasis on the selective annulation reaction with biselectrophiles. In part three, we will summarize the applications of heterocyclic enamines in the syntheses of alkaloids and related pharmaceutically useful compounds. We will focus on the synthesis of pyrrolidine, piperidine, bipyrrolidine, perhydroindolizine, perhydroquinolizine, and other fused heterocyclic alkaloids. Synthesis of antibacterial and other bioactival compounds using heterocyclic enamines protocol will also be included.

Fungal transformation of monoterpenes was less frequently studied compared to other natural products until a few decades ago due to their toxicity, volatility and general difficulty in handling. In recent years, however, researchers have paid much attention and reported the fungal transformation of acyclic, monocyclic and bicyclic monoterpene hydrocarbons, and oxygenated monoterpenes and their derivatives. The present review thus summarizes the fungal transformation of acyclic, mono- and bicyclic monoterpene hydrocarbons, oxygenated monoterpenes and their derivatives. The bacterial transformations are not included in the present review.