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This review chapter describes the syntheses and reactions of five-membered heterocyclic ring systems containing nitrogen and sulfur (reported during 2015). The importance of these p-rich heterocycles in medicinal chemistry and natural products is also covered.

The review covers drugs that have been approved by the U.S. Food and Drug Administration during the period 2000 to the present time that contains heterocyclic rings. Some 57% of the drugs currently in use contain at least one heterocycle.

This review chapter focuses on the syntheses and reactions of thiazoles, benzothiazoles, thiazolines, isothiazolines, thiadiazoles, and selenodiazoles (reported during 2012). The importance of these π-rich heterocycles in medicinal chemistry and natural products is also covered.

Publisher Summary This chapter discusses the syntheses and reactions of these 5-membered heterocyclic ring systems containing nitrogen and sulfur (or selenium). The importance of these π-rich heterocycles in medicinal chemistry and natural products is also discussed. The chapter discusses the synthesis of thiazoles, fused thiazoles, and thiazolines. Reactions of thiazoles and fused derivatives are also discussed in the chapter. The first practical, large-scale synthesis of 2-amino-5-fluorothiazole employs the reaction of dilithiated 2-butoxycarbonylaminothiazole with N-fluorobenzenesulfonimide (NFSi). This reaction generates a 70:15 mixture of the desired fluorinated thiazole and the sulphone, and after three consecutive recrystallizations thiazole is isolated in 35–40% yield. This procedure has been utilized to prepare multikilogram quantities of 2-amino-5-fluorothiazole that is a heterocyclic amine component of a series of glucokinase inhibitors. A new methodology for direct phosphonation of thiazoles has been developed. Reaction of substituted thiazoles with dimethyl or diethyl phosphates in the presence of manganese (III) acetate dihydrate provides 5-dimethyl or diethyl-phosphonothiazoles.

Publisher Summary Fredericamycin A is an antitumor antibiotic of unusual structure. The compound has attracted a great deal of attention, especially from synthetic chemists; the substance is a powerful antitumor agent. What makes this antitumor agent special is the fact that its structure type is unique; consequently, the identification of structure-activity relationships might reveal new mechanisms for destroying cancer cells. This chapter discusses how fredericamycin A works except for the fact that it inhibits topoisomerases I and II. The other characteristic of fredericamycin A is that the structure is complicated, and hence, if the biological implications of synthetic work—the possibility of finding useful structure-activity correlations—are not significant, then, at least, the chemical experiments would probably lead to something new. The chapter presents a number of related examples. In each case the appropriate ketone is converted into its selenoacetal and then into the selenium-stabilized carbanion.