Knowledge base: Adam Mickiewicz University

Settings and your account

Back

Regio- and steroselective functionalizotion of aglycone of Spiramycin via cascade strategy

Katarzyna Pyta-Klich

Abstract

Functionalization of the 16-membered aglycone of spiramycin, using intramolecular cascade strategy has been developed. The new α,β,γ,δ–unsaturated aglycone of Spiramycin have been obtained via multistep reactions: at the first step aldehyde group of Spiramycin was protected by dimethyl acetal moiety, next OH group at the C2’ carbon atom was acetylated. Then upon treatment of NaH, the stereospecific product of three cascade reactions: intramolecular transesterification and double E1cB elimination of acetate and sugar moiety was isolated. In the next stage aldehyde group of the product was deprotected. Obtained a new diastereopure derivative SPR5 has opened a new path of 16-membered macrolides not avaible to date. A new series of bicyclic type derivatives of α,β,γ,δ–unsaturated aglycone of Spiramycin via intramolecular regio- and stereospecific Michael or Michael type addition were synthesized. Next eleven SPRH1-SPRH11 novel triazole derivatives via Huisgen 1,3-dipolar cycloaddition have been synthesized. Structures, conformations and configuration of all products of cascade reactions and Husigen cycloadditions were determined by ESI, IR, B88LYP DFT method and NMR methods: 1H, 13C, HSQC, HMBC, COSY, NOESY. Biological tests and molecular docking at the ribosome tunnel of new derivatives have been performed to porpose model of ligand–tunnel interactions with the large 50S subunit.
Record ID
UAM2cb3fdeb53be445a80aec430a47a040d
Diploma type
Doctor of Philosophy
Author
Title in Polish
Funkcjonalizacja aglikonu Spiramycyny przez zastosowanie regio- i stereoselektywnych reakcji kaskadowych
Title in English
Regio- and steroselective functionalizotion of aglycone of Spiramycin via cascade strategy
Language
pol (pl) Polish
Certifying Unit
Wydział Chemii [nowa struktura organizacyjna] (SNŚ/WC)
Scientific discipline (2.0)
6.5 chemical sciences
Status
Finished
Year of creation
2016
Defense Date
31-05-2016
Title date
31-05-2016
Supervisor
URL
http://hdl.handle.net/10593/14671 Opening in a new tab
Keywords in English
antibiotics, spiramycin, regioselectivity, stereoselectivity, cascades
Abstract in English
Functionalization of the 16-membered aglycone of spiramycin, using intramolecular cascade strategy has been developed. The new α,β,γ,δ–unsaturated aglycone of Spiramycin have been obtained via multistep reactions: at the first step aldehyde group of Spiramycin was protected by dimethyl acetal moiety, next OH group at the C2’ carbon atom was acetylated. Then upon treatment of NaH, the stereospecific product of three cascade reactions: intramolecular transesterification and double E1cB elimination of acetate and sugar moiety was isolated. In the next stage aldehyde group of the product was deprotected. Obtained a new diastereopure derivative SPR5 has opened a new path of 16-membered macrolides not avaible to date. A new series of bicyclic type derivatives of α,β,γ,δ–unsaturated aglycone of Spiramycin via intramolecular regio- and stereospecific Michael or Michael type addition were synthesized. Next eleven SPRH1-SPRH11 novel triazole derivatives via Huisgen 1,3-dipolar cycloaddition have been synthesized. Structures, conformations and configuration of all products of cascade reactions and Husigen cycloadditions were determined by ESI, IR, B88LYP DFT method and NMR methods: 1H, 13C, HSQC, HMBC, COSY, NOESY. Biological tests and molecular docking at the ribosome tunnel of new derivatives have been performed to porpose model of ligand–tunnel interactions with the large 50S subunit.
Thesis file
  • File: 1
    Klich Katarzyna Rozprawa Doktorska.pdf
Request a WCAG compliant version

Uniform Resource Identifier
https://researchportal.amu.edu.pl/info/phd/UAM2cb3fdeb53be445a80aec430a47a040d/
URN
urn:amu-prod:UAM2cb3fdeb53be445a80aec430a47a040d

Confirmation
Are you sure?
Report incorrect data on this page
clipboard