New approaches to the synthesis of bioactive aza-heterocycles based on domino-reactions of oxacarbenium ions, iminium ion vinologs and donor-acceptor cyclopropanes
New approaches to the synthesis of bioactive aza-heterocycles based on domino-reactions of oxacarbenium ions, iminium ion vinologs and donor-acceptor cyclopropanes
Year 2017
Project goals
- Synthesis of heterocyclic systems using domino-reactions.
- Development of new efficient approaches to bioactive heterocyclic compounds on the basis of simple transformations of easily available starter compounds.
- Synthesis of molecules subclasses of bio-isosteric to certain bioactive natural compounds and synthetic medicines based on polyfunctional compounds used as multicentric reagents in organic synthesis.
- Development of new multicomponent reactions based on interaction of isonitriles and azides with 3-alkylidene salts and cationic intermediates, generated from ketals and polyfunctional acetals
Project leader
All participants
Andrey Malkov
PhD, Professor of Chemistry
Professor of Organic Chemistry, Loughborough University, England
Project results
development of new multicomponent reactions based on the interaction of isonitriles and azides with 3-alkylidene salts and cationic intermediates generated from ketals and polyfunctional acetals;
creation of efficient approaches to the synthesis of bioactive derivatives of tetrazole and indole - analogues of natural nucleosides and certain oncology meidcation.
new approaches to bioactive derivatives of pyrroloquinoline, pyrroloquinazoline, pyrrolodibenzazepine, which are close structural analogues of a number of alkaloids and synthetic drugs, were developed. Based on the developed approaches, there is a plan to carry out a complete synthesis of a number of natural compounds (crispip A, trollip, mescatolam). The further testing of physiological activity of synthesized compounds is proposed.
Equipment
All list
Liquid chromatograph Shimadzu LC-20
It is intended for the separation of analytes into components, its detection, identification and quantitative analysis by high-performance liquid chromatography (HPLC).
Benchtop Dual-Channel Spectrometer SpinSolv Carbon
An optical device used in spectroscopic studies to accumulate a spectrum, its quantitative processing and subsequent analysis using various analytical methods. The decomposed spectrum is obtained by recording the fluorescence after exposure to the substance under the test with radiation (X-ray or laser radiation, spark action, etc.). Essentially, this device measures the intensity and energy (wavelength, frequency) of radiation and other characteristics can be recorded, for example, the polarization state. The term “spectrometer” is applied to devices operating in a wide range of wavelengths: from gamma to infrared range.
IKA RV 8V Rotary Evaporator
It is designed to remove residual solvent from the reaction mixture.
IKA Heating Mantles
Designed for reactions with external heating.
IKA RST basic Magnetic Stirrer
Designed for carrying out reactions with stirring and, if necessary, heating.
Top-pan balane UW-220H Shimadzu
Designed for weighing work material with a certain and prescribed accuracy.
Application area
- in pharmaceuticals (antitussives, analgesic, analgesics; testing of ready-to-use and approved products for potential use in the preparation of a medicinal drugs);
- in chemotherapy (in the treatment of many cancers, and in some cases it is particularly effective - for example, in hematologic cancer; in other cases it is used as a multimodality treatment - for example, to prevent dissemination of the tumor, some chemotherapy regimens include several drugs which allows for the maintainenace of the overall effectiveness of the scheme and reduction of the side effects of each of the applied drugs, sometimes сhemotherapeutic preparations (compounds) are administered topically (e.g. in urinary bladder);
- oncotherapy (the development of the formulation for the preparation of drugs on synthesized target compounds).