A First Diversity-Oriented N-Maleopimarimido-Isocyanide for Multicomponent Reactions: Synthesis, Application, and In...

Area of Science:

• Organic Chemistry
• Medicinal Chemistry
• Drug Discovery

Background:

• Multicomponent reactions (IMCRs) are efficient for complex molecule synthesis.
• Isocyanides are versatile building blocks in IMCRs.
• Abietane diterpenes are natural products with diverse bioactivities.

Purpose of the Study:

• To synthesize a novel abietane diterpene isocyanide.
• To explore its utility in Passerini, Ugi, and azido-Ugi reactions.
• To evaluate the drug-like properties and potential therapeutic applications of the synthesized compounds.

Main Methods:

• Synthesis of abietane diterpene isocyanide from levopimaric acid-maleic anhydride adduct.
• Application of Passerini, Ugi, and azido-Ugi reactions.
• Physicochemical analysis, in silico ADME, drug-likeness, target prediction, and toxicity studies (SwissADME, ProTox-III).

Main Results:

• Successful synthesis of abietane diterpene isocyanide and its derivatives (α-acyloxy- and α-acylaminocarboxamides, tetrazoles) in high yields.
• Compounds exhibit moderate lipophilicity, good membrane permeability and solubility, and high gastrointestinal absorption.
• Selective CYP3A4 inhibition with low predicted toxicity (hepato- and carcinogenicity).

Conclusions:

• Abietane diterpene isocyanide is a valuable building block for diverse abietane derivatives.
• The synthesized compounds possess favorable drug-like properties and potential for therapeutic applications.
• These derivatives show potential as cytotoxic, antiviral, and anti-inflammatory agents.