Current Organic Chemistry - Volume 8, Issue 12, 2004

The Baeyer-Villiger oxidation of ketones represents a powerful methodology in synthesis to break carbon-carbon bonds in an oxygen insertion process. Since the discovery of the reaction by Adolf Baeyer and Victor Villiger in 1899 substantial progress has been made to understand the mechanism, to predict migratory preference, and to apply this conversion in preparative chemistry. Chiral Baeyer-Villiger oxidation of cyclic ketones allows rapid access to asymmetric lactones as valuable intermediates in organic chemistry and frequently encountered precursors in enantioselective synthesis. In recent years, organometal catalysts and other artificial catalytic entities have been continuously improved and represent promising approaches for future process developments. Complementing this strategy, biocatalysis offers a “green chemistry” alternative for this transformation. This review will give a comprehensive summary of strategies to perform Baeyer-Villiger reactions in an enantioselective manner. A discussion of scope and limitations of both organometallic approaches and biocatalytic methods includes substrate profiles, improvement of optical purity, and implications upon scale-up.

Flash vacuum pyrolysis is an interesting methodology for studying reaction mechanisms as well as synthesis. Its characteristics of submitting the molecule to high temperature (350 - 900ºC) in a vacuum system (∼ 10-2 Torr) for a short time (∼ 10-2s) makes possible to isolate kinetically controlled products and, in some cases, to avoid consecutive reactions. Studies of reaction mechanisms may include kinetic and non-kinetic methods, and of course, the knowledge of reaction mechanisms and the influence of substituents in it, makes possible the synthetic application of these reactions. In this review reactions of different nitrogen heterocycles will be divided by type of reaction, such as isomerizations, radical reactions, nitrogen extrusion, eliminations, and reactions of the side chain. Special attention will be dedicated to kinetic measurements because it is not a common way to study flash vacuum pyrolysis reactions but they give important information about reaction mechanisms. An improvement of flash vacuum pyrolysis reactions with the use of solid catalysts will also be discussed. These catalysts have two effects, in some cases they lower the reaction temperature and in some others there is a change of the reaction with formation of different products. These results extend the possibilities of flash vacuum pyrolysis of a single substrate.

2(5H)-Furanone derivatives are a large family of heterocycles that include synthetically useful compounds, several natural products and drugs with diverse biological activities. From the 1960, there has been a continuous interest in the development of efficient methods for preparation of these heterocycles and in their synthetic applications. The studies in these fields have been summarised and discussed in several excellent reviews, some of which have been recently published. The present article aims at completing the picture of these studies and highlights the most recent results from our and other and our laboratories which have been considered only shortly in previous reviews or have not been reviewed at all. In particular, it deals with the preparation and reactivity of 3,4- dichloro-5-hydroxy-2(5H)-furanone (also called mucochloric acid) and 3,4-dibromo-5-hydroxy-2(5H)-furanone (also called mucobromic acid) and the synthetic applications of these inexpensive, highly functionalised synthons. These applications illustrate that these mucohalic acids can provide a simple and convenient entry to a wide variety of interesting organic compounds and are mainly concerned with the selective and efficient preparation of variously substituted 2(5H)-furanone derivatives, including natural and unnatural compounds, which exhibit antiinflammatory activity or are characterised by potent cytotoxic activities against human cancer cell lines. Nevertheless, our attempt to tell the “whole story” of mucochloric and mucobromic acids from 1873 up to the present day is also concerned with a discussion on the use of these substances for preparation of stereodefined acyclic unsaturated dihalogenated derivatives and sulfur- or nitrogen-containing heterocycles, including members, which are precursors to agrochemically important substances.

The porphyrins and related tetrapyrrole systems are among the most widely studied of all macrocyclic compounds. In fact, in one capacity or another these versatile molecules have influenced nearly all disciplines in chemistry. In recent years, efforts are underway to develop tetrahydroporphyrin-based (bacteriochlorin) compounds with long wavelength absorption in the range of 700-800 nm as photosensitizers for photodynamic therapy (PDT). This review article summarizes the synthetic methodologies that have been developed for the preparation of a variety of bacteriochlorins, either from porphyrins or chlorin systems.

Over the course of the last decades, phosphinic peptides have emerged as an extremely important class of Zn-metalloprotease inhibitors. The intense interest in these compounds in the field of medicinal chemistry reflects a conjunction of synthetic advances and ideal physicochemical and biochemical properties. Among the latter, the optimal tetrahedral structure of phosphinic acid moiety, which perfectly fills the requirements of transition state theory, clearly defines the mechanistical frame of their function as metalloprotease inhibitors (transition state analogues, TSA). In particular, phosphinic peptides are peptidic isosters containing a chemically stable phosphinic acid moiety which mimics the transition state tetrahedral geometry of a scissile peptide bond during enzymatic hydrolysis. Moreover, the ionic interactions of phosphinic oxyanion with catalytic Zn2+ combined with the substrate-like primary interactions of pseudopeptidic backbone with enzyme's active site, can aid the rationalization of the design and development of potent and selective Zn-protease inhibitors. In these review, we aim to resume the major achievements in this field over the last decades. In the first part, the fundamental principles of phosphinopeptidic chemistry, as these have been established by the pioneers of the field, as well as the synthesis of first-generation inhibitors are presented. In the second part, accounting as a turning point the introduction of SPPS and combinatorial practices in the field, a comprehensive description of all the recent synthetic novelties as well as the outstanding applications of phosphinopeptidic derivatives in enzymatic, biochemical and crystallographic studies is attempted.