Structural derivatization strategies of natural phenols by semi-synthesis and total-synthesis

Abstract

Structural derivatization of natural products has been a continuing and irreplaceable source of novel drug leads. Natural phenols are a broad category of natural products with wide pharmacological activity and have offered plenty of clinical drugs. However, the structural complexity and wide variety of natural phenols leads to the difficulty of structural derivatization. Skeleton analysis indicated most types of natural phenols can be structured by the combination and extension of three common fragments containing phenol, phenylpropanoid and benzoyl. Based on these fragments, the derivatization strategies of natural phenols were unified and comprehensively analyzed in this review. In addition to classical methods, advanced strategies with high selectivity, efficiency and practicality were emphasized. Total synthesis strategies of typical fragments such as stilbenes, chalcones and flavonoids were also covered and analyzed as the supplementary for supporting the diversity-oriented derivatization of natural phenols.

In Silico and In Vitro Antiviral Activity Evaluation of Prodigiosin from Serratia marcescens Against Enterovirus 71

“…Consistent with our findings, most of these compounds were suggested to interfere with the early stages of the viral replication cycle (in adsorption, penetration, and RNA replication), except matrine, which was shown to regulate host immune response (in vivo). Since highly efficacious natural compounds are extremely difficult to discover, structural modification and derivative synthesis may be considered to enhance their efficacy (Lin et al, 2022;Xu et al, 2022). Furthermore, Shang, Xu, and Yin (2013) reported that 6-amino acid peptide (LVLQTM) was capable of binding the active site and inhibiting 2A protease (Falah et al, 2012), metrifudil and N6-benzyladenosine inhibited 2C helicase (Arita et al, 2008), and rupintrivir inhibited 3C protease ( Kuo et al, 2008;Cui et al, 2011;Tan et al, 2016).…”

Removing Neighboring Ring Influence in Monocyclic B–OH Diazaborines: Properties and Reactivity as Phenolic Bioisosteres with Dynamic Hydroxy Exchange

“…A single uncharacterized example of a monocyclic B–OH containing diazaborine was reported as a bioconjugate linker in a DNA-encoded library, while the related 1,2-azaborine has remained unreported . In light of the vast occurrence of phenol-containing substructures in biologically active natural and synthetic compounds, , the preparation of boranol-containing oxaza- and diazaborines has significant implications in bioisosterism and drug discovery. This sort of novel chemotype may show unique properties amenable to engineering gain-of-function through additional H-bonding and reversible covalent exchange with the pseudophenolic boranol unit.…”

Sensitive and selective phenol sensing in denitrifying Aromatoleum aromaticum EbN1 T

“…Phenolic compounds are widespread constituents of dissolved organic matter in the terrestrial and marine realm, with continuous input from natural as well as anthropogenic sources. They represent major building blocks of abundant biopolymers such as the plant cell wall inherent lignin ( 1 ) and are essential for sclerotizing the exoskeletons of insects ( 2 ). Phenolic compounds, as significant constituents of fossil energy sources, are released during extraction and processing [e.g., reference ( 3 )].…”