Current Organic Chemistry - Volume 8, Issue 16, 2004

Lithiated γ -chloroalkyl heterocycles are useful intermediates for the stereoselective construction of a number of heterocyclic systems. Prof. S. Florio, and co-workers University of Bari, Italy, discuss the potential and intricacies of this type of chemistry. Synthesis and pharmacological properties of 4-thiazolidones is the theme in the second chapter contributed by Drs R.B. Lesyk and B.S. Zimenkovsky from Danylo Halytsky University, Lviv, Ukraine. The final two chapters, dealing with reductive cyclisation in the synthesis of 5- and 6-membered N-heterocycles have been contributed by Drs P.G. Tsoungas and A.I. Diplas form Athens and Patras, Greece, respectively.

The chemistry of lithiated α-chloroalkylheterocycles such as α-chloroalkylbenzothiazoles, - benzotriazoles, -pyridines, -triazines, -thiazoles and -oxazolines has been reviewed. The synthetic application of this kind of chemistry for the stereoselective preparation of heteroaryl cyclopropanes, oxiranes, aziridines, alkenes and functionalised nitroarenes through a Darzens-type reaction, has been especially emphasised.

The potential of 4-thiazolidones (2,4-thiazolidinediones, 2-thioxo(imino)-4-thiazolidones) as drugs is under consideration by the pharmaceutical science since the beginning of the XX century. During recent years a new phase has been seen in this field. Centerarian history of synthetic research possibilities of these heterocycles lead to diversity in modelling biologically active compounds using 4-thiazolidone scaffolds. Modification of the 4- thiazolidone cycle on 2-, 3-, 4- or 5-position is successful to achieve synthetic products with a wide spectrum of pharmacological activity and has received considerable attention in this review. Currently 4-thiazolidones are considered as a new class of antidiabetic (insulin-sensitising) drugs and potent aldose reductase inhibitors, which possess potential for the treatment of diabetes complications (cataract, nephropathy, neuropathy). Novel 4- thiazolidones are undergoing different stages of clinical trials as potential thyromimetic, antimicrobial, antiviral, anti-ischaermic, cardiovascular, anticancer drugs.

The versatility and potential of reductive cyclisation as a route to 5-membered N-heterocyclic structures of diverse complexity is demonstrated through selected examples.

The versatility and potential of reductive cyclisation as a route to 6-membered N-heterocyclic structures of diverse complexity is demonstrated through selected examples.