Current Organic Chemistry - Volume 7, Issue 18, 2003

Isoquinoline alkaloids are a small group of natural products with widespread occurrence in nature and also playing a very important role in the secondary metabolism of numerous vegetal families. In this context, during the last years the stereoselective synthesis of differently substituted tetrahydroisoquinolines has been a field of increasing interest in synthetic organic chemistry in which many research groups have focused much of their efforts. On the other hand, enantiopure α-amino acids and their derivatives have shown to be excellent tools for the organic chemist working in the field of asymmetric synthesis, either acting as chiral building blocks, auxiliaries or ligands. In this review, the different approaches for the asymmetric synthesis of substituted tetrahydroisoquinolines reported during the last years, in which chiral nonracemic α-amino acids or derivatives have played a crucial role will be presented. We have limited to the general procedures developed for the introduction of the desired substituents at the different positions of the tetrahydroisoquinoline core in a stereocontrolled way. However, some cases in which the obtained heterocycles have additionally been used as key synthetic intermediates for the easy preparation of other, naturally occurring, more elaborated, isoquinoline alkaloids have been covered.

The literature survey about the title subject since 1985 is presented. The new heterocycles are classified by the tetracyanoethylene (TCNE) reaction type. Accordingly, four classes of TCNE-derivative heterocycles can be identified: (i) reaction products obtained by nucleophilic attack on tetracyanocyclopropanes, which in turn are formed from the reaction of TCNE with aliphatic monobromoderivatives; (ii) products resulting from the thermal decomposition of unstable charge-transfer compounds of TCNE and an electron-donor; (iii) Diels-Alder cycloadducts between TCNE and a diene; (iv) products derived from previously unknown reaction of TCNE. The most interesting new heterocyclic compounds belong to the last (iv) class of TCNE-derivatives, where the 2-(5-amino-3,4-dicyano-2H-pyrrol-2-ylidene)-1,1,2-tricyanoethanide (L'), synthesized for the first time by the author after the reductive autocondensation of TCNE promoted by Lewis acids, occurs too. Further, we report on the properties of L' both as metal-chelating ligand and material for sensor applications. L' undergoes an intramolecular cyclization to the 1,2,6,7-tetracyano-3,5-diimino-3,5-dihydropyrrolizinide (L) on coordination to transition metal cations. A number of metal-complexes of L, either mono- (ML) or bispyrrolizinates, M(L)2, have been isolated and structurally characterized. The most interesting property of these species is that they are metal-phthalocyanine-like dyes and thus they may be useful for the interpretation of the electronic structure of porphyrinic systems. The protonation of L' furnishes the neutral 5-amino-3-imino-1,2,6,7- tetracyano-3H-pyrrolizine (HL). Like other similar conjugated heteropolycyclic molecules and their conjugated anions and complexes, L' and all its derivatives show suitable properties for application in the construction of optochemical sensors, potentially useful for detecting species of environmental interest.

There are diverse classes of compounds in the arsenal of synthetic organic chemists, which are of immense use in the synthesis of natural products. The class of α-diazocarbonyls is one of them. The compounds of this class are often used for the generation of reactive intermediates such as carbenoids and ketenes. The reactions of these intermediates have been used in the synthesis of a wide variety of organic compounds including several natural products. This article describes briefly the preparation of α-diazocarbonyls, their reactions through carbenoid and ketenes, and application of these reactions in the synthesis of several complex and biologically important natural products.

To perform its biochemical functions, a protein usually folds into a well defined, highly ordered structure. Subtle changes in conformation are frequently used in nature to modulate or regulate protein's functions. It is, thus, critical to identify these changes in order to fully comprehend how proteins perform their biological functions. A variety of spectrometry techniques, including X-ray crystallography, nuclear magnetic resonance (NMR), circular dichroism (CD), fluorescence, infrared and Raman spectroscopies, and mass spectrometry (MS), are in current use for the conformational analysis of proteins and peptides. These techniques are complementary and provide important information related to the conformation and folding / unfolding dynamics of proteins. CD is wellestablished for measuring the secondary structural elements of a protein and fluorescence provides information on the environment of aromatic moieties. X-ray crystallography and NMR both provide structural details down to atomic resolution. Mass spectrometry is a recent addition in the field of conformational analysis. Isotope hydrogen exchange, in combination with NMR and MS, has been a highly successful approach in the detection of conformational changes in proteins. In this review article, a short description of the basic principles of these techniques and recent representative examples of their applications in conformational analysis of proteins and peptides are described.

Major aspects of the synthetic utility of 1,3-diketones are reviewed with special emphasis being placed on the regioselectivity of the transformations. The unsymmetrical 1,3-diketone moiety may contain up to five nucleophilic and two electrophilic centers that may only slightly differ in reactivity; therefore, it seems almost impossible to carry out chemical transformations with substrate selectively at only one specific center. However, in many cases it is possible, and in the present review answers to this question as well as many other useful synthetic applications of 1,3-diketones for the construction of carbocycles and heterocycles, and their modern implication in enantioselective, combinatorial, solid phase, and multistep organic syntheses are summarized.