Synthesis of a Library of Terpenoid Alkaloid-Like Compounds Containing Medium-Sized Rings via Reconstruction of the Humulene Skeleton.
Chemistry
; 30(48): e202402082, 2024 Aug 27.
Article
en En
| MEDLINE
| ID: mdl-38897925
ABSTRACT
The construction of a chemical library based on natural products is a promising method for the synthesis of natural product-like compounds. In this study, we synthesized a terpenoid alkaloid-like compound library based on the humulene skeleton. Our strategy, which enables access to diverse ring systems such as 11-membered monocyclic, oxabicyclic, and medium-sized aza ring-containing scaffolds, involves the introduction of a nitrogen atom, an intermolecular C-O bond formation via Lewis acid-mediated epoxide-opening transannulation, and a ring-reconstruction strategy based on olefin metathesis. A cheminformatics analysis based on their structural and physicochemical properties revealed that the synthesized compounds have high three-dimensionality and high natural product likeness scores but with structural novelty. The usefulness of the terpenoid alkaloid-like compound library for drug discovery and the accessibility to structure-activity relationship studies were validated by performing an assay for osteoclast-specific tartrate-resistant acid phosphatase activity, resulting in the identification of a seed compound for bone-resorptive diseases such as osteoporosis.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Alcaloides
/
Sesquiterpenos Monocíclicos
Idioma:
En
Revista:
Chemistry
Asunto de la revista:
QUIMICA
Año:
2024
Tipo del documento:
Article
País de afiliación:
Japón
Pais de publicación:
Alemania