2,2,2-Trichloro-4-methoxy-1,3,2-benzodioxaphosphole in the reactions with terminal acetylenes

© 2020 2,2,2-Trichloro-4-methoxy-1,3,2-benzodioxaphosphole reacts with arylacetylenes or 3-chloropropyne to give 2,7-dichloro-5-methoxy-4-aryl(haloalkyl)-1,2-benzoxaphosphinine 2-oxides. Hydrolysis of the latter leads to the opening of the oxaphosphinine ring and formation of (E)-2-(4-chloro-2- methoxy-6 hydroxyphenyl)ethenylphosphonic acid

Cell-Modulating Effect of Poly(Aspartic Acid) and Its Complex with Cationic Polyaspartamide

© 2020, Springer Science+Business Media, LLC, part of Springer Nature. In this communication, poly(aspartic acid) (pAsp), its fluorescently labeled conjugate with lucifer yellow ethylenediamine (pAsp–LY), and 2,2-dimethyl-1,3-propanediamine-derived cationic polyaspartamide (pDmpa) were synthesized by liquid-phase method. Octamer of L-aspartic acid (L-Asp8) was also obtained by solid-phase synthesis. pDmpa interacted with both pAsp and model plasmid DNA to form compact nanosized interpolymer complexes, which showed different colloidal properties. Effective cellular uptake of pAsp–LY by NIH 3T3 fibroblasts was detected by confocal microscopy. Pre-complexation of pAsp–LY with pDmpa did not noticeably increase intracellular accumulation of the conjugate. Both pAsp and L-Asp8 were found to increase viability of murine 3T3 cells and human skin fibroblasts at μg/mL concentrations according to the MTT assay (24 h). This effect was observed along with moderate prooxidant activity of the peptides in the cells according to the DCFDA fluorescence assay. The results suggest that aspartic acid-based peptides per se are capable of penetrating mammalian cells and affecting their metabolic activity. The peptides can be complexed with their cationic derivative, i.e., pDmpa polyaspartamide, to develop nanosized formulations of pAsp and its conjugates

Reaction of R-pulegone with P–H phosphonium salts

© 2020 The reaction of the R-pulegone with P–H-phosphonium salts gives the corresponding 8-phosphonio-p-menthan-3-one salts with high regio- and stereoselectivity. The structure of salts was determined by NMR and IR spectroscopy, mass spectrometry and X-ray diffraction analysis

Synthesis of C-29-phosphonium derivatives of 3,28-diacetoxylup-20(29)-en-30-oic acid

© 2020, Springer Science+Business Media LLC. 3β,28-Diacetoxylup-20(29)-en-30-oic acid (obtained via oxidation of betulin diacetate) enters the addition reaction with P—H-phosphonium salts (triarylphosphonium trifluoroacetates) under mild conditions to afford β-carboxyalkylphosphonium salts. Structure and composition of the resulting compounds were confirmed by NMR and IR spectroscopy, mass spectrometry, and elemental analysis

Synthesis, anticancer, and antibacterial activity of betulinic and betulonic acid C-28-triphenylphosphonium conjugates with variable alkyl linker length

© 2020 Bentham Science Publishers. Background: Conjugation of triterpenoids such as betulinic acid 1 with the Triphenylphosphonium (TPP) group is a powerful approach to generating medicinal compounds. Their development proposes structure optimization in respect of availability and activity towards target cells and organelles. Selection of 1 or its pre-cursor betulonic acid 2 and the optimal linker is of particular importance for drug candidate identification among the TPP-triterpenoid conjugates. Objective: In this study, new C-28-TPP conjugated derivatives of 1 and 2 with the alkyl/alkoxyalkyl linkers of variable length were synthesized and compared regarding their anticancer, antibacterial, and mitochondria-targeted effects. Methods: The TPP conjugates of 1 and 2 [6a-f, 7a-f] were synthesized by the reaction of halogenalkyl esters [3a-f, 4a-f, 5] with triphenylphosphine in acetonitrile upon heating. Cytotoxicity (MTT assay), antibacterial activity (microdilution assay), and mitochondrial effects (flow cytofluorometry) were studied. Results: Conjugation with the TPP group greatly increased the cytotoxicity of the triterpenoids up to 30 times. The conjugates were up to 10-17 times more active against MCF-7 (IC50 = 0.17µM, 72h, 6c) and PC-3 (IC50 = 0.14µM, 72h, 6a) cancer cells than for human skin fibroblasts. The enhanced antibacterial (bactericidal) activity of the TPP-triterpenoid conjugates with MIC for Gram-positive bacteria as low as 2µM (6a, 7a) was for the first time revealed. The conjugates were found to effectively inhibit fluorescence of 2′,7′-dichlorofluorescin probe in the cytosol upon oxidation, decrease transmembrane potential, and increase superoxide radical level in mitochondria. Conclusion: Relationships between the effects and structure of the TPP-triterpenoid conjugates were evaluated and are discussed. Based on the results, 6a can be selected for further preclinical investigation as a potential anticancer compound

3,28-Diacetoxylup-20(29)-ene-30-oic Acid and Its ω-Bromoalkyl Esters

© 2020, Pleiades Publishing, Ltd. Abstract: A convenient procedure has been developed for the synthesis of3β,28-diacetoxylup-20(29)-en-30-oic acid via oxidation of 3β,28-di-O-acetylbetulin with selenium dioxide in aqueousethanol on heating, followed by oxidation of 3β,28-diacetoxylup-20(29)-en-30-althus formed with sodium chlorite in tert-butyl alcohol. The alkylation of3β,28-diacetoxylup-20(29)-en-30-oic acid with 1,3-dibrompropane and1,5-dibromopentane in boiling acetonitrile in the presence of potassiumcarbonate afforded the corresponding ω-bromoalkyl esters in high yields

Synthesis and in vitro evaluation of triphenylphosphonium derivatives of acetylsalicylic and salicylic acids: structure-dependent interactions with cancer cells, bacteria, and mitochondria

Salicylic acid (SA) remains one of the most fruitful natural compounds to generate drug molecules with versatile activities. In this study, effective synthesis of SA and acetylsalicylic acid (ASA) derivatives with a carrier triphenylphoshonium (TPP) group was proposed. A series of SA and ASA conjugates linked with the TPP group via alkyl chain linker (C3-C10) was synthesized. The conjugates showed enhanced TPP-mediated cytotoxicity towards MCF-7, Caco-2, PC-3 cells in proportion to the linker length. 7e, 8e (C9), and 7f (C10) were the most active against the cancer cells with IC50 = 0.6–1.9 µM while were less toxic for HSF. Similarly, antibacterial (bactericidal) activity of the compounds against S. aureus increased with the linker elongation. The lowest MIC for SA and ASA derivatives were 4 and 1 µM, respectively. The TPP conjugates induced early linker length-dependent mitochondria depolarization and concurrent superoxide radical production in the cancer cells. The most lipophilic conjugates were found to specifically interact with ROS probe 2′,7′-dichlorofluorescin diacetate, forming mixed aggregates with the probe and inhibiting its fluorescence upon oxidation. These interactions were exploited to probe the compounds inside living cells. The results identify 7e and 7f as promising mitochondria-modulating and anticancer agents with increased cellular availability. [Figure not available: see fulltext.

Rational design 2-hydroxypropylphosphonium salts as cancer cell mitochondria-targeted vectors: Synthesis, structure, and biological properties

It has been shown for a wide range of epoxy compounds that their interaction with triphenylphosphonium triflate occurs with a high chemoselectivity and leads to the formation of (2-hydroxypropyl)triphenylphosphonium triflates 3 substituted in the 3-position with an alkoxy, alkylcarboxyl group, or halogen, which were isolated in a high yield. Using the methodology for the disclosure of epichlorohydrin with alcohols in the presence of boron trifluoride ether-ate, followed by the substitution of iodine for chlorine and treatment with triphenylphosphine, 2-hydroxypropyltriphenylphosphonium iodides 4 were also obtained. The molecular and supramolec-ular structure of the obtained phosphonium salts was established, and their high antitumor activity was revealed in relation to duodenal adenocarcinoma. The formation of liposomal systems based on phosphonium salt 3 and L-α-phosphatidylcholine (PC) was employed for improving the bioavailabil-ity and reducing the toxicity. They were produced by the thin film rehydration method and exhibited cytotoxic properties. This rational design of phosphonium salts 3 and 4 has promising potential of new vectors for targeted delivery into mitochondria of tumor cells

Modern Trends of Organic Chemistry in Russian Universities

This review is devoted to the scientific achievements of the departments of organic chemistry in higher schools of Russia within the past decade. © 2018, Pleiades Publishing, Ltd