Mini-Reviews in Organic Chemistry - Volume 1, Issue 4, 2004

Densely hydroxylated, medium-sized carbocycles and their analogues have long been a somewhat neglected molecular progeny for two reasons: (a) the synthesis of such expanded and functionality rich rings is quite a challenging task that remains partially unsolved and (b) the biological significance of these constructs has not yet been thoroughly appreciated. This account mainly discusses recent approaches used to deal with this rare class of carbohydrate mimics with particular emphasis being placed on annulative strategies using ring-closing metathesis, aldol-based ring closure, intramolecular nitrile oxide and nitrone cycloaddition, and the Claisen rearrangement. Less documented annulative and non-annulative procedures including free-radical cyclisation, intramolecular coupling, and ring expansion and manipulation are also considered.

Pin1, a phospho-Ser / Thr-Pro specific PPIase, participates in many biological processes. Recently, through designing substrate mimetics, or library screening, several classes of Pin1 inhibitors have been discovered. Some polyaromatic compounds, including juglone, as well as peptide mimetics containing both proline and phosphate, have been demonstrated to inhibit biological functions of Pin1.

The four isomers of thienothiophene have long been considered only for academic interest. Their usefulness in material science and biology has led to a renewal of their chemistry. The present paper reports the newest synthetic methods after the first review by Litvinov and Gol'dfarb in 1976.

The use of thiosemicarbazide in organic synthesis has become a classical strategy for the synthesis of several heterocycles. Their reactions with compounds containing C=O and C=N groups is an elegant method for the preparation of biologically active compounds viz. triazoles and thiazoles. The ease of forming C-N and C=N bonds as opposed to N-N bond formation is reflected in their extensive use for the preparation of these heterocycles. As the internal nitrogen atom of the hydrazine fragment is a softer nucleophilic centre than the more powerful terminal nitrogen, reagents susceptible to nucleophilic attack by the terminal nitrogen undergo cyclisation to afford the aforesaid heterocycles in excellent yields, even under mild reaction conditions. The present review attempts to summarise the cyclisation reactions of thiosemicarbazide derivatives yielding 1, 2, 4-triazoles and thiazoles.

β-(N,N-dialkylamino)propiophenones (ArCOCHR1CH2NR2) are compounds with special synthetic interest not only because many of them are biologically active, but also because they posses two different electrophilic reaction centers (i. e. carbonyl group and the β-carbon atom), which can be attacked by ambifunctional nucleophilic reagents. This property makes them attractive starting materials in medicinal chemistry as valuable building blocks for ring closure reactions to form mainly five, six and seven-membered heterocyclic compounds. Additionally, the presence of α-methylene active hydrogen atoms in such compounds also opens new possibilities for ring closure reaction as recently has been published. A selection of representative examples about structural and biological properties of the title compounds, synthetic methods and ring closure reactions leading to nitrogenated heterocyclic systems are described in this review.

Quinone methides (QMs) are reactive intermediates involved in a large number of chemical and biological processes such as enzyme inhibition, DNA alkylation and cross-linking. Their electrophilicity towards amines, thiols, water, amino acids and peptides has been kinetically measured in aqueous solution. The alkylation process is often thermally and photochemically reversible and the resulting adducts may act as QM carriers.

This account deals with recent progress in the study on the synthesis of fluorine containing heterocycles via the cycloaddition reactions of some fluorine-containing dienophiles or dipolarophiles. It includes two main parts: (1) the 1,3-dipolar cycloaddition reactions to five-membered fluorinated heterocycles; (2) the (hetero) Diels-Alder reactions to six-membered fluorinated heterocycles.