Mini-Reviews in Organic Chemistry - Volume 10, Issue 2, 2013

Mitochondria are known to be the main players in important mitochondrial bioenergetic functions such as ATP synthesis, thermoregulatory energy dissipation, Ca2+ transport, generation of reactive oxygen species and mediation of intrinsic apoptosis. Naturally occurring polyamines, due to their high pka are almost completely protonated at physiological pH and behave as polycations in their interactions with mitochondrial membranes. Thanks to these interactions, polyamines are transported electrophoretically into the mitochondrial matrix, where they exhibit a number of effects of significant importance for the above-mentioned mitochondrial functions, particularly inner membrane permeability transition (MPT). This event is closely correlated with the intrinsic occurrence of apoptosis, so that the effect of polyamine interactions with mitochondria has important implications in the pathophysiological consequences of inducing apoptosis, i.e., protection against cancer and neurodegenerative diseases. This review also provides some answers to the old debated problems regarding the possible interactions of polyamines with mitochondrial DNA, overcoming of the Born charging energy by spermine, the Δψ threshold value for polyamine transport, and protection of MPT by spermine in in vivo conditions. In conclusion, the old question: “What do polyamines do?” is partially solved.

The pyridazine moiety is an important and frequent antifeeedant, insecticidal, herbicidal, molluscicidal, plant growth regulatory activity and other agrochemical structural feature of many biologically active compounds. Recently, much attention has been focused on pyridazinone derivatives for their broad-spectrum activities. Substituted pyridazine derivatives were also reported to show antibacterial, antifungal, antiviral, properties. Promoted by the above observations, the combination of two or more heterocyclic and non-heterocyclic systems enhances the biological profile many-fold than its parent nuclei. We considered some compounds bearing pyridazinone in a molecular framework.

The discovery of phosphodiesterase 10A (PDE10A) enzyme ligands as therapeutic agents in the treatment of central nervous system diseases, especially schizophrenia and Huntington’s disease nowadays is a competitive field developing rapidly, with many pharmaceutical companies involved in identifying a huge diversity of chemical scaffolds and molecular architectures for PDE10A interaction. Owing to the importance of this field, the aim of this review is to survey the chemistry and biological properties of linear and angular tricyclic-based heterocycles incorporating valid pharmacophores for PDE10A activity.

Salacinol was isolated as the first naturally occurring sulfonium type α-glucosidase inhibitor from Salacia reticulata, a large woody, climbing plant widely distributed in Sri Lanka and South India, in 1997. This compound presents a quite unique zwitterionic sulfonium sulfate structure and its α-glucosidase inhibitory activity (in vitro) was revealed to be as potent as those of anti-diabetics used in clinic. Since then, great efforts have been made to discover other bioactive ingredients as potent α-glucosidase inhibitors from the same genus of plants, which directly led to the identification of several side chain analogs of salacinol such as kotalanol, salaprinol and ponkoranol together with their de-Osulfonated analogs. In the mean time, much attention has been focused on the total syntheses, structure activity relationship (SAR) studies on this group of natural products in order to design molecules with improved activities. Thus, as a possible result of present findings, this class of natural products has the potential to become lead compounds with potent α- glucosidase inhibitory activities, which could be further developed to a new class of hypoglycemic drug candidates. The present review was developed as a summary of the recent researches of total synthesis and SAR of this series of natural products. In addition, several important structural determinants including the most recent discoveries on SAR are summarized, which may provide new insights into the development of novel anti-diabetic agents.

Sulfonamides (SO2–NH-) have been the center of drug structures as they are quite stable and well tolerated in human beings. The sulfonamides are very important protected intermediates of amines, with several types of biological activities. Due to the broad applicability of sulfonamides, it is desirable to find general and effective methods for their synthesis. Different methods have been adopted to synthesize sulfonamides. Here is a comprehensive review which provides several of the most common and recent methods of sulfonamide synthesis: via sulfonyl chloride; starting from thiols, sulfonic acids, sulfenamide and sulfonate esters; or using indium, copper, and palladium as catalysts or Grignard reagents and metal oxides.

Complementary hydrogen-bonding arrays are very important for the genetic information storage and transmission. Inspired by natural complementary hydrogen-bonding arrays, researchers have been developing many artificial examples, which have been used in the construction of functional materials. The aim of this review is to highlight the complementary hydrogen-bonding arrays for supramolecular polymerizations.

Recently, chemical cross coupling reactions have emerged as a powerful tool in the hands of synthetic organic chemist to synthesize complicated organic scaffolds like drugs, natural products, optical devices and industrially important materials. Stable N-Heterocyclic Carbene (NHC) acts as an important catalyst system in various cross coupling reactions. This review describes various strategies used for the synthesis of free and stable NHCs. Historical developments made in the propagation of the idea of free and stable carbene have also keenly been illustrated in the introduction of this review.

Chiral sulfoxides are extensively used in synthesis of chiral drugs, total synthesis of natural products and organic synthesis. Among them, chiral sulfoxide drugs in market or under research mostly have nitrogen-containing substructures. In common titanium catalysts have better catalytic property in asymmetric oxidation of these nitrogencontaining sulfide precursors than other catalysts. The ligands of these titanium catalysts have tartarate, BINOL and other diols, salens and others. Proton pump inhibitors, anti-inflammatory drugs, anti-cancer drugs, antibiotics, platelet adhesion inhibitors, antipsychotic drugs, lipid regulators, potassium channel openers, neurokinin inhibitors and so on are valuable chiral sulfoxide drugs. The research advances of synthesis of various chiral sulfoxide drugs catalyzed by titanium are described in this review.