Catecholamine Derivatives: Natural Occurrence, Structural Diversity, and Biological Activity

Abstract

Catecholamines (CAs) are aromatic amines containing a 3,4-dihydroxyphenyl nucleus and an amine side chain. Representative CAs included the endogenous neurotransmitters epinephrine, norepinephrine, and dopamine. CAs and their derivatives are good resources for the development of sympathomimetic or central nervous system drugs, while they also provide ligands important for G-protein coupled receptor (GPCR) research. CAs are of broad interest in the fields of chemical, biological, medical, and material sciences due to their high adhesive capacities, chemical reactivities, metal-chelating abilities, redox activities, excellent biocompatibilities, and ease of degradability. Herein, we summarize CAs derivatives isolated and identified from microorganisms, plants, insects, and marine invertebrates in recent decades, alongside their wide range of reported biological activities. The aim of this review is to provide an overview of the structural and biological diversities of CAs, the regularity of their natural occurrences, and insights toward future research and development pertinent to this important class of naturally occurring compounds.

Natural Product-Inspired Dopamine Receptor Ligands

“…The endogenous neurotransmitter dopamine ( 1 , Figure ) functions to activate dopamine receptors with the affinity trend of D 3 R ( K i = 3 nM) > D 4.4 R ( K i = 6.4 nM) > D 2S R ( K i = 12.5 nM) > D 2L R ( K i = 16 nM) ≫ D 5 R ( K i = 228 nM) ≫ D 1 R ( K i = 2340 nM) (D 4.4 R is a human polymorphic variant). − While dopamine cannot be used as a CNS drug, as it cannot cross the protective BBB, it can still be used as a peripheral vasostimulant for the treatment of low heart rate, cardiac arrest, and low blood pressure. , Originally believed to be a biologically inactive amino acid, l -3,4-dihydroxyphenylalanine ( l -DOPA, 21 , Figure ) was isolated from seedlings of Vicia faba beans in 1913. , l -DOPA is transported across the BBB by the large neutral amino acid transporter (LAT1) and is subsequently decarboxylated to dopamine by the endogenous enzyme aromatic l -amino acid decarboxylase. l -DOPA bypasses the rate-limiting step in dopamine synthesis (involving the enzyme tyrosine hydroxylase) and is more quickly converted to dopamine than the biosynthetic starting material for dopamine production, the amino acids l -tyrosine or l -phenylalanine.…”

Simplified Modular Access to Enantiopure 1,2-Aminoalcohols via Ni-Electrocatalytic Decarboxylative Arylation

“…Enantiopure aminoalcohols are ubiquitous in natural products, active pharmaceutical ingredients (APIs), and agrochemicals. The 2-amino-1-arylethanol unit, in particular, is frequently encountered (Figure A). − For example, econazole ( 1 ) is widely used as an antifungal medication; , indacaterol ( 2 ) and salmeterol ( 3 ) are effective bronchodilators and enlisted as top-selling small-molecule drugs; and a unique boron-containing molecule GSK-656 ( 4 ) is a promising antituberculosis drug with a new mechanism of action. , Synthetic approaches to molecules of this sort generally rely on a deliberate construction of the aminoalcohol in a stepwise fashion rather than a modular installation through cross-coupling. − Indeed, constructing the chiral aminoalcohol motifs in 1 – 4 requires multiple steps, all of which are reliant on polar bond retrosynthetic analysis (Figure B). Thus, asymmetric epoxidation, asymmetric ketone reduction followed by S N 2 with a nitrogen-based nucleophile, and an asymmetric Henry reaction followed by hydrogenation of the nitro group are the go-to transformations to access such structures.…”

“…The 2-amino-1-arylethanol unit, in particular, is frequently encountered ( Figure 1 A). 1 − 4 For example, econazole ( 1 ) is widely used as an antifungal medication; 5 , 6 indacaterol ( 2 ) and salmeterol ( 3 ) are effective bronchodilators and enlisted as top-selling small-molecule drugs; 7 and a unique boron-containing molecule GSK-656 ( 4 ) is a promising antituberculosis drug with a new mechanism of action. 8 , 9 Synthetic approaches to molecules of this sort generally rely on a deliberate construction of the aminoalcohol in a stepwise fashion rather than a modular installation through cross-coupling.…”

Meirols A–C: Bioactive Catecholic Compounds from the Marine-Derived Fungus Meira sp. 1210CH-42

“…Alternatively, a biologically active natural product may inspire the discovery of clinically useful drug agents by offering insights into types of structural features that may prove valuable. Catechols, benzene derivatives containing a 3,4-dihydroxyphenyl group, have recently been discovered as diverse derivatives in microorganisms, plants, insects, and marine organisms [3]. Their ubiquity can be attributed to their rich redox chemistry, ability to cross-link through complex and irreversible oxidation mechanisms, excellent chelating properties, and the various ways in which vicinal hydroxyl groups interact with surfaces of significantly diverse chemical and physical characteristics [4,5].…”

“…Aligned with their structural variety, catecholamines have been reported to exhibit a broad spectrum of biological activities, encompassing antiparasitic, antibacterial, metal-chelating, anti-inflammatory, immune-modulation, wound-healing, antioxidant, Mar. Drugs 2024, 22, 87 2 of 10 neuroprotective, nephroprotective, and metabolic regulation activities [3]. Hence, novel catechol compounds derived from natural sources will serve as a promising foundation for broadening their potential biological and medical applications.…”