Mini-Reviews in Organic Chemistry - Volume 5, Issue 3, 2008

The recent advances of PET using biomolecules, such as peptides, monoclonal antibodies, oligonucleotides, and glycoproteins will be described. So far, PET of biomolecules has been used mainly for diagnosis of cancers. The biomolecules have been conjugated with DOTA ligand, labeled with radiometals as the β+ emitter, and targeted to specific tumors, where they have enabled visualization of even small metastatic lesions, due to the high sensitivity of the PET scanners.

Molecularly imprinted polymers (MIPs) are highly cross-linked porous polymers with a predetermined selectivity for a given analyte or structurally related compounds, that make them ideal materials to be used in a wide range of areas including chemical sensing, separation, drug delivery and catalysis. The aim of this short review is to outline the molecular imprinting technology with particular reference to the development of MIPs as artificial receptors for the recognition of nucleotide bases and their derivatives.

Apoptosis is a programmed cell death process, critical for normal cellular development and tissue homeostasis. B-cell lymphocyte/leukemia 2 (Bcl-2) family proteins are important regulators of apoptosis. Numerous studies have demonstrated that over-expressing anti-apoptotic Bcl-2 proteins is one mechanism for cancer cells to acquire resistance against cancer chemotherapies, suggesting antagonizing these proteins would be a potential approach to overcoming such drug resistance. This review briefly discusses the principle and the recent advances in the development of such antagonists, with some highlights about several promising antagonists.

The 5‘-terminus of eukaryotic messenger RNA (mRNA) molecules contains a unique ‘cap’ structure: 7- methylguanosine (m7G) linked by a 5‘-5‘-triphosphate bridge to the first nucleoside in the standard polymer chain. This 5‘- cap is recognized by numerous enzymes involved in the transport and translation of mRNA, as well as its processing, both in terms of generating mature mRNA from the initial transcript and its natural degradation. In vitro generation of capped RNAs uses a cap analog in which two nucleosides are joined in a 5‘-5‘ triphosphate linkage, allowing incorporation of the cap along with the first nucleotide in the polymer chain. The conventional cap analog, m7G[5‘]ppp[5‘]G, has a 3‘-OH on both nucleoside moieties, resulting in the incorporation of the dinucleotide in either orientation. This results in one-third to one-half of the mRNAs containing a non-methylated cap and a methylated initial nucleotide. These ‘reverse cap’ structures bind poorly to elF4E and other cap binding proteins, greatly reducing the overall translational efficiency in vitro and biological activity in vivo. This drawback of the conventional cap analog has been addressed by creating an “anti-reverse cap analog” (ARCA), m2 7, 3'-OG[5‘]ppp[5‘]G, in which the 3‘-OH of the ribose connected to the m7Guo moiety is replaced with a 3‘-O-methyl group, allowing incorporation only in the forward orientation due to the presence of the single extendable 3‘-OH group. In addition to the chemical modification at the 3‘-OH group of the ribose connected to the m7G moiety, modifications at the 2‘-OH group also preclude attachment of a second nucleotide by polymerase, again forcing the forward orientation. This mini-review focuses on recent developments in the synthesis of novel cap analogs, highlighting modifications at several positions including; the heterocyclic bases, the sugars, and the α-, β-, and γ-phosphates in the triphosphate chain, and assessing their impact on biological activity.

This review relates a new access to the piperidine ring by intramolecular cyclization of acyl iminium and iminium ions substituted by an allylsilyl side chain as an internal Π-nucleophile. This methodology was applied to the synthesis of piperidine alkaloids

This review covers some of the contributions of the authors to the peptidomimetic field. These contributions explore the potential of amino acid-derived α-amino nitriles for generating molecular diversity. Cyanomethyleneamino pseudopeptide analogues of several bioactive peptides and α-quaternary amino nitriles were obtained via a modified three component Strecker synthesis. Taking advantage of the reactivity of the cyano group and the diverse functionality of amino acid derivatives, cyanomethyleneamino pseudopeptides were transformed into carbamoylmethyleneamino and branched pseudopeptides or privileged heterocyclic scaffolds, such as: piperazine, pyrazino[1,2-c]pyrimidine, 1,4- benzodiazepine, and novel indole derivatives, including some spirocyclic compounds.

The development of efficient catalytic system for selective organic transformation is currently one of the challenging tasks in synthetic organic chemistry. In recent years, N-hydroxyphthalimide (NHPI) has been recognized as a valuable catalyst for the aerobic oxidation of various organic compounds under mild conditions. The generation of the phthalimide-N-oxyl (PINO) radicals from its precursor NHPI, can be achieved by using different ways including electrochemical, enzymatic and chemical methods. Among all of these methods, the use of lead tetraacetate for the PINO radicals' generation seems to be the most peculiar, several kinetic and mechanistic “anomalies” for this catalytic system being reported.

Macrocyclic Schiff bases form an important class of macrocyclic host systems, which are formed by self condensation of a diamine with a diformyl compound. Chiral modification of macrocyclic Schiff bases with different central cavity sizes were recently developed and explored. This mini-review will discuss some of the synthetic strategies, solid state crystal structures, and recent applications of different [n+n] chiral macrocyclic Schiff bases.

Cardanol, a low-cost largely available renewable material obtained from distillation of CNSL (Cashew Nut Shell Liquid), has been used for the preparation of fine chemicals and hybrid materials. The long chain attached to the meta position of the phenolic ring of cardanol makes this compound a unique natural source because it confers to all derivatives, particular properties (good solubility, good processability, interesting physical properties and so on). New fine chemicals as well as new cardanol hybrid materials combined with porphyrins, phthalocyanines and fullerenes have been synthesized recently, developing at the same time new synthetic strategies for the preparation of new eco-friendly fine chemicals, composites and functional organic materials. The aim of this review is also to show that the chemistry of cardanol is becoming a stimulating area in academic and industrial research.

Phospholipids (PLs) are important constituents of cellular membranes. HOCl is a reactive oxygen species (ROS) generated under inflammatory conditions and capable of reacting with (a) the head group of PLs and (b) the olefinic groups of their fatty acyl residues under the preferred generation of chloramines and chlorohydrines, respectively. This review discusses these products, their stabilities and in vivo relevance. Additionally, important methods (spectroscopic as well as mass spectrometric techniques) to analyze these products are compared.