abstract
Betulinic acid (BA) and its natural analogues betulin (BN), betulonic (BoA), and 23-hydroxybetulinic (HBA) acids are lupane-type pentacyclic triterpenoids. They are present in many plants and display important biological activities. This review focuses on the chemical transformations used to functionalize BA/BN/BoA/HBA in order to obtain new derivatives with improved biological activity, covering the period since 2013 to 2018. It is divided by the main chemical transformations reported in the literature, including amination, esterification, alkylation, sulfonation, copper(I)-catalyzed alkyne-azide cycloaddition, palladium-catalyzed cross-coupling, hydroxylation, and aldol condensation reactions. In addition, the synthesis of heterocycle-fused BA/HBA derivatives and polymerBA conjugates are also addressed. The new derivatives are mainly used as antitumor agents, but there are other biological applications such as antimalarial activity, drug delivery, bioimaging, among others.
keywords
PENTACYCLIC TRITERPENE DERIVATIVES; BIOLOGICAL EVALUATION; ANTITUMOR-ACTIVITY; LUPANE TRITERPENOIDS; CYTOTOXIC EVALUATION; IN-VITRO; MATURATION INHIBITOR; DESIGN; ESTERS; HYBRIDS
subject category
Biochemistry & Molecular Biology; Chemistry
authors
Sousa, JLC; Freire, CSR; Silvestre, AJD; Silva, AMS
our authors
Armando Jorge Domingues Silvestre
Full professor
Carmen Sofia da Rocha Freire Barros
Coordinating Researcher
Joana Lia Cardoso de Sousa
Post-Doc Fellowshipacknowledgements
This work is financed by Portugal 2020 through FEDER in the frame of POCI and in the scope of the projects: MultiBiorefinery (POCI-01-0145-FEDER-016403), CICECO-Aveiro Institute of Materials CTM/50011 (POCI-01-0145-FEDER-007679), and QOPNA Research Unit (UID/QUI/00062/2019), co-financed by FCT/MCTES.