Current Organic Chemistry - Volume 23, Issue 5, 2019

Dammarane-type ginsenosides are a class of tetracyclic triterpenoids with the same dammarane skeleton. These compounds have a wide range of pharmaceutical applications for neoplasms, diabetes mellitus and other metabolic syndromes, hyperlipidemia, cardiovascular and cerebrovascular diseases, aging, neurodegenerative disease, bone disease, liver disease, kidney disease, gastrointestinal disease and other conditions. In order to develop new antineoplastic drugs, it is necessary to improve the bioactivity, solubility and bioavailability, and illuminate the mechanism of action of these compounds. A large number of ginsenosides and their derivatives have been separated from certain herbs or synthesized, and tested in various experiments, such as anti-proliferation, induction of apoptosis, cell cycle arrest and cancer-involved signaling pathways. In this review, we have summarized the progress in structural modification, shed light on the structure-activity relationship (SAR), and offered insights into biosynthesis-structural association. This review is expected to provide a preliminary guide for the modification and synthesis of ginsenosides.

The heavy dependence on fossil fuels raises many concerns on unsustainability and negative environmental impact. Biomass valorization to sustainable chemicals and fuels is an attractive strategy to reduce the reliance on fossil fuel sources. Gasification, liquefaction and pyrolysis are the main thermochemical technologies for biomass conversion. Gasification occurs at high temperature and yields the gas (syngas) as the main product. Liquefaction is conducted at low temperature but high pressure, which mainly produces liquid product with high quality. Biomass pyrolysis is performed at a moderate temperature and gives a primarily liquid product (bio-oil). However, the liquid product from biomass conversion is not advantageous for direct use as a fuel. Compared to liquefaction, pyrolysis is favorable when the aim is to produce the maximum amount of the liquid product from the biomass. Hydrotreating for bio-oil upgrading requires a large amount of expensive hydrogen, making this process costly. Catalytic cracking of bio-oil to reduce the oxygen content leads to a low H/C ratio. Methanolysis is a novel process that utilizes methane instead of hydrogen for biomass conversion. The feasibility studies show that this approach is quite promising. The original complexity of biomass and variation in composition make the composition of the product from biomass conversion unpredictable. Model compounds are employed to better understand the reaction mechanism and develop an optimal catalyst for obtaining the desired product. The major thermochemical technologies and the mechanism based on model compound investigations are reviewed in the article.

Functionalized gem-bisphosphonic acid derivatives being pyrophosphate isosteres are of great synthetic and biological interest since they are currently the most important class of drugs developed for the treatment of diseases associated with the disorder of calcium metabolism, including osteoporosis, Paget’s disease, and hypercalcemia. In this article, we will try to give an in-depth overview of the methods for obtaining α- heteroatom-substituted methylenebisphosphonates and acquaint the reader with the synthetic strategies that are used to develop biologically important compounds of this type.

The synthesis and chemistry of heterocyclic N-oxide derivatives such as those from pyridine and indazole are very well-known due to their usefulness as versatile synthetic intermediates and their biological importance. These classes of organic compounds have been demonstrated in many interesting and amazing functionalities, particularly vital in the areas including metal complexes formation, catalysts design, asymmetric catalysis and synthesis, and medicinal applications (some potent N-oxide compounds with anticancer, antibacterial, anti-inflammatory activity, etc.). Therefore, the heterocyclic N-oxide motif has been successfully employed in a number of recent advanced chemistry and drug development investigations. In the present review, our primary aim was to provide a relevant summary focusing on the topics of organic synthesis and medical application potential of the compounds cited, which could be attractive and give some insights to researchers in the field. Therefore, we mainly highlight the importance of heterocyclic N-oxide derivatives including those synthesized from imidazole, indazole, indole, pyridazine, pyrazine, pyridine, and pyrimidine in organic syntheses and catalysis, and drug applications. Over the past years, a number of reviews have been published on the organic synthesis and catalysis of N-oxides. We thus concentrated on highlighting those rarely mentioned or recently reported systems.

Standard therapy of Organophosphorus Compound (OPC) poisoning with oxime-type acetylcholinesterase (AChE) reactivators is unsatisfactory. New bispyridinium oximes have therefore been synthesized. This review summarizes in vitro characteristics of established (pralidoxime, obidoxime, trimedoxime, HI-6) and experimental (K-)oximes, and compares their protective efficacy in vivo, when administered shortly after exposure to Diisopropylfluorophosphate (DFP) and three OPC pesticides (ethyl-paraoxon, methylparaoxon, azinphos-methyl) in the same experimental setting. In addition to reactivating cholinesterase, oximes also inhibit this enzyme; strongest AChE inhibition (IC50 rat blood: 1-9 μM) is observed in vitro for the oximes with a xylene linker (K-107, K-108, K-113). AChE inhibition is weakest for K-27, K-48 and HI-6 (IC50 >500 μM). Intrinsic AChE inhibition of oximes in vitro (IC50, rat) is strongly correlated with their LD50 (rat): oximes with a high IC50 (K-27, K-48, pralidoxime, obidoxime) also show a high LD50, making them relatively non-toxic, whereas oximes K-107, K-108 and K-113 (low IC50 and LD50) are far more toxic. When given in vivo after OP exposure, best protection is conferred by K-27, reducing the relative risk of death to 16-58% of controls, which is significantly superior to pralidoxime in DFP-, ethyl-paraoxon- and methylparaoxon- exposure, and to obidoxime in ethyl-paraoxon- and methyl-paraoxon-exposure. Marked reduction in mortality is also achieved by K-48, K-53, K-74 and K-75, whereas K-107, K-108 and K-113 have no or only a very weak mortality-reducing effect. K-27 is the most promising K-oxime due to its strong reactivation potency, weak cholinesterase inhibition and high LD50, allowing administration in large, very efficacious dosages.