Current Organic Chemistry - Volume 15, Issue 3, 2011

This review covers literature on organocatalyzed enantioselective α-heterofunctionalization of carbonyl compounds from 2006 to 2009. In this review, we will consider those reactions in which a new carbon-heteroatom bond is formed using a chiral organic molecule as catalyst, excluding those processes, which involve the modification on the hybridization of a previously functionalized carbonyl compound. Using this straightforward synthetic strategy, a wide range of valuable chiral building blocks such as α-amino acids, α-amino alcohols, epoxides, 1,2-diols, α-sulfenylated, α-selenenylated and α-halogenated carbonyl derivatives can be obtained by this simple and advantageous methodology.

Macrolides are produced by various Streptomyces strains and make up a large group of compounds among antibiotics used against various infectious diseases. There are many criteria of classification of compounds of this type but natural macrolides usually consist of 14- or 16- membered macrocyclic lactone rings and differ from each other by the type and number of sugar moieties attached as well as by their various modes of binding to the aglycone part. Recently, renewed interest in synthesis of 16-membered macrolide derivatives has been evoked by their interesting biological properties, relatively good gastric tolerance and low tendency for producing allergy and inducing resistance. Many reviews have been devoted to the biological properties of various macrolides but only a few of them have been focused on a very important natural and semi-synthetic 16-membered macrolides and the fast growing group of their derivatives. I have, therefore, attempted to review the past and recent advances in the modifications and biological investigation of selected 16- membered leucomycin type macrolides group, including natural leucomycins (kitasamycins), spiramycins, midecamycins, semi-synthetic rokitamycin and miocamycin as well as 16-membered macrolides not belonging to the leucomycin group - tylosins and desmycosins, important from the biological application point of view. This review is dedicated to organic chemists who wish to stay abreast with the modification and properties of 16-membered macrolides and their derivatives. Despite enormous number of studies of diverse derivatives of leucomycin-type macrolides as well as tylosins and desmycosins, the 16-membered macrolides, due to their high biological potential and many possibilities for further modifications, have not yet revealed all their secrets.

The publications appeared in the last eleven years on the topic of the preparation of organolithium reagents by nondeprotonating methodologies and starting from non-halogenated substrates have been covered in the present revision. In this part, the carbon-heteroatom bond cleavage under reductive conditions has been considered, carbon-oxygen and carbon-sulfur bond cleavages (both in acyclic or cyclic systems) being of paramount importance. Additionally, other bond scissions, such as carbon-nitrogen, carbon- phosphorous, carbon-fluorine, carbon-silicon, carbon-selenium and carbon-tellurium bonds are recorded.

Cyclic sulfites, sulfates and sulfamidates derived from saccharides have emerged as valuable and versatile synthons for the preparation of a wide variety of modified sugars and sugar related compounds owing to the combination of the easily and efficient formation of these chemical sulfur derivatives from diols and aminoalcohols with the high chemical stability and enhanced reactivity of those functions towards nucleophiles. The state-of-the-art in this area is covered in the present review using the relative position of the diols and the aminoalcohol functions on the saccharide skeleton and the nature of the nucleophilic reagent (oxygenated nucleophiles, halogens, sulphur nucleophiles, nitrogen nucleophiles, and carbon nucleophiles) as expositive criteria. A comprehensive outlook of the applications of these sulfur derivatives in the preparation of compounds such as azido sugars, halo sugars, thiosugars, pseudo-saccharides, radiotracers, enzymatic inhibitors, anticonvulsant agents, surfactants amongst others is also given.

A number of oxime reactivators have been synthesized and studied for the antidotal treatment of poisoning by toxic organophosphorus agents, and several oximes are currently available to reactivate the organophosphorus agents-induced acetylcholinesterase inhibition. However, there is no oxime with broad spectrum suitable for the antidotal treatment of poisoning with various organoposphorus warfare agents as well as insecticides. In addition, current available oximes have very limited brain-blood barrier (BBB) penetration, even though hydrophobic toxic organophosphorus agents can easily penetrate BBB. Therefore, the development of BBB permeable oxime reactivators is one of great challenges in these days. In this review, we summarize advances in the synthesis and reactivation evaluation of oximes that have been studied in our research group. Various approaches have been employed to design these analogs; for example, bispyridinium oximes with (CH2)2O(CH2)2 linkers, (CH2)O(CH2)nO(CH2) linkers and (CH2)n linkers as well as fluorinated bis-pyridinium oximes.