Current Organic Chemistry - Volume 13, Issue 16, 2009

With the development of catalytic asymmetric methodologies directed to the synthesis of biologically active molecules during the last years, organocatalysis has emerged as a powerful tool. The organocatalytic approach is complementary to transition metal-based catalysis within the field of asymmetric synthesis and several research groups have achieved great aims in this area by the first time. The enantioselective Friedel-Crafts alkylation reaction of indoles is a powerful and direct method for preparing enantiomerically pure 3- or 2-substituted indolyl compounds and a number of organocatalyzed syntheses of these indolyl substrates have been developed in recent years. Due to the abundance of indole moieties in enantiomerically pure biologically interesting natural compounds asymmetric strategies have arisen as important processes of synthesis. These important alkylation processes including the addition of indole to α,β-unsaturated carbonyl compounds, nitroalkenes and imines as well as their applications will be discussed in this review.

The Mitsunobu reaction involves the “redox” condensation of an acidic pronucleophile with a primary or secondary alcohol promoted by a reactive phosphonium salt derived from an alkyl or aryl phosphine and an azo compound. The synthetic utility of the reaction is demonstrated by the wide range of acidic pronucleophiles that are tolerated including carboxylic acids, phenols, imides, hydroxamates, thiols, thioamides, fluorinated alcohols, oximes, pyridinium and imidazolium salts, pyrimidine bases, β-ketoesters and trimethylmethane tricarboxylate (TMET) thereby generating a variety of functionally diverse molecules. The focus of this review is to highlight the recent development of new or alternative reagents and purification strategies for the Mitsunobu reaction with a discussion of their suitability for modern drug design supported by selected examples from the literature.

[1n]Paracyclophanes ([1n]PCPs) do not often appear in cyclophane chemistry because their synthetic strategies are limited compared to those of general o-, m-, p-[mn]cyclophanes. However, the highly symmetrical and relatively rigid structure of [1n]PCPs has attracted the interest of chemists in the fields of host-guest and molecular recognition chemistry. Some categories of [1n]PCP have been synthesized for application in polymer chemistry, while others were synthesized for synthetic interest or with the aim of investigating their chemical properties. The aims of synthesis are diverse, but the special structures connecting the benzene rings with the various elements are surely attractive from an aesthetic point of view. In this review, the synthetic strategies, structures, and some applications of [1n]PCPs are surveyed.

3-Amino-4-(phenyl or p-methoxyphenyl)-6-pyridin-3-ylthieno[2,3-b]-pyridine-2-carboxamide and 3-amino-4- (phenyl or p-methoxyphenyl)-6-pyridin-3-ylthieno[2,3-b]pyridine-2-carbonitrile were used as the starting materials aiming to obtain the newly synthesized pyridothieno-pyrimidines, pyridothienotriazines and pyridothienoxazines via their reactions with several reagents e.g. CS2, HCOOH, CH(OEt)3, Ac2O and HNO2. These newly synthesized heterocyclic compounds were tested as anti-Alzheimer and anti COX-2 agents and their structures were elucidated by considering the data of IR, 1H NMR, mass spectra and elemental analyses.

Matrix-assisted laser desorption and ionization (MALDI) mass spectrometry (MS) - often but not exclusively combined with time-of-flight (TOF) mass analyzers - is one of the most successful “soft” ionization methods that is applicable to a very broad range of analytes. Although the ionization process is still widely unknown and a matter of intense research, it is commonly accepted that the matrix plays a crucial role. The development of and the search for useful matrix compounds, however, was - and still is - an empirical process because only some obvious properties (vacuum stability, high absorption at the laser wavelength, etc.) that must be fulfilled by a compound to become a useful MALDI matrix are known so far. Although MALDI MS is primarily used for the analysis of polar biopolymers, such as proteins and nucleic acids, the focus of this review is on the analysis of apolar molecules with special emphasis on lipids and phospholipids. Beside established organic matrix molecules, such as cinnamic or benzoic acid derivatives, the advantages and drawbacks of liquid crystalline matrices and mixtures of common matrices will be also shortly discussed. It will be shown that only the careful selection of the matrix enables the detection of the compounds of interest. It will also be demonstrated that mixture analysis and the quantitative analysis of small molecules can be accurately performed only if the matrix is carefully selected. Finally, some basic principles how useful matrix compounds can be de novo “designed” will be introduced.