Current Organic Chemistry - Volume 19, Issue 20, 2015

The presence of organic molecules in meteorites clearly indicates the occurrence of a large panel of chemical reactions in space conditions. The scenarios in which these transformations take place are diverse and fascinating: proto-stellar nebulae, dense or rarefied clouds of interstellar and cosmic dust particles, comets, meteorites, proto-planets and asteroids. High energy particles (cosmic rays and solar winds), heat, electromagnetic radiations, and radioactive decays continuously interact with simple chemical precursors to yield new complex derivatives. Some of these reactions are more relevant than others in the process of origin of life. The prebiotic chemistry in space conditions finally determines the synthesis of molecules that may play a key role in the organization of the first genetic and metabolic systems. Once synthesized some molecules can be transported through the universe until habitable planets. The description of the full set of these reactions is extremely complex and necessarily incomplete. In this review, some relevant prebiotic processes in space conditions are described with particular attention to the catalytic role played by stellar objects in the transformation of ubiquitous chemical precursors, such as formamide, formaldehyde and hydrogen cyanide. Thus, amino acids, nucleobases, sugars, lipids and carboxylic acids emerge as very easily synthesizable molecules in the universe ready to join in the first living cell.

(+)-Lactacystin (1) is a natural substance that was firstly isolated in 1991 from bacteria of the genus Streptomyces, and it was studied for its ability to inhibit cell growth. Its mechanism of action is the inhibition of the 20S proteasome, which together with two 19S regulatory sub-units makes up the 26S proteasome complex; this is a part of the ubiquitin-proteasome pathway (UPP) in eukaryotic cells. 1 accumulates particularly in damaged cells, where the misfolded proteins occur, and subsequently it is able to arrest the cell cycle in the G1 phase by inhibition of the 20S proteasome, thus inducing apoptosis of the cell. 1 and its derivatives (e.g. omuralide (2), salinosporamide A (3), cinnabaramide A (4)) were tested as potential drug candidates for the treatment of arthritis, asthma and cancer. 1 is activated in vitro at neutral pH, when there is spontaneous transformation to (+)-lactacystin-β-lactone (omuralide, 2), which is able to cross the cell membrane and irreversibly inhibit the 20S proteasome. The first total synthesis of 1 was published in 1992 by Corey et al. Soon after, different approaches to the total synthesis of 1 then followed, including formal total synthesis using various asymmetric catalyzed reactions, such as catalytic Sharpless asymmetric dihydroxylation, epoxidation, aldol condensation, Overman [3,3]-sigmatropic rearrangement and many others. This study describes the structure and function of the ubiquitin-proteasome system, and also discloses various approaches leading to the total synthesis of 1.

Effects of oxygen depletion on cellular membranes are still poorly understood. Amphiphilic molecules are known to modulate the plasma membrane lipid bilayer’s physical properties; in turn, mechanical properties of the lipid bilayer affect signal transduction through numerous mechanosensitive transmembrane proteins including ion channels, receptor tyrosine kinases, NADPH oxidases and G-protein coupled receptors. Thus, the concentration of oxygen in/at the lipid bilayer may modulate its mechanical properties. Here we propose that: (i) under hypoxia, the plasma membrane lipid bilayer would become oxygen depleted, (ii) depletion of oxygen molecules might induce mechanical stress in the lipid bilayer, and (iii) hypoxia-induced mechanical stress in the lipid bilayer activates mechanosensitive transmembrane proteins and downstream signalling pathways. We provide evidence – on the basis of published experimental data – that there can be links between oxygen depletioninduced mechanical stress in the membrane and activation of some mechanisms participating in oxygen sensing, including reactive oxygen species (ROS) produced by mitochondrial complex III, ROS generated at the plasma membrane by NADPH oxidases, ion channels of the transient receptor potential family and increase in intracellular Ca2+ and stabilization of hypoxia-inducible factor 1α (HIF-1α).

During the years different types of N-sulfonic acids are prepared and used as efficient catalysts for the promotion of various types of organic reactions. These methods lead to high yields of the products under mild conditions during acceptable reaction times. These catalysts are recyclable and can be reused in their activities.

A convenient and practical approach for the total synthesis of Xestoaminol C has been accomplished with 16.43% overall yield from commercially available D-glucose. The synthesis involves SN2 type centre inversion with azido group, Staudinger reaction, Wittig olefination and Pearlman’s catalytic hydrogenation.