Work

Synthesis of Heterospirocycles through Gold‐(I) Catalysis: Useful Building Blocks for Medicinal Chemistry

Year: 2021

Type: article

Abstract: Gold‐(I) catalysis was used for the intramolecular cyclization of tertiary alcohols with terminal alkynes to form diverse aza‐spirocycles. The reaction was carried out with low catalyst loading under microwave irradiation to give both sulfonylated and acylated spirocyclic nitrogen derivatives. Gram scale spirocyclization was carried out to demonstrate the robustness of the reaction. An intramolecular Mizoroki‐Heck reaction was performed to give several tetracyclic spirocycles. Double bond reduction and selective protecting group manipulation gave spiropiperazine and spiromorpholine derivatives. These compounds were incorporated into biologically relevant scaffolds to give the first selective spirocyclic inhibitors of LIMK1. magnified image

Source: Advanced Synthesis & Catalysis

DOI: 10.1002/adsc.202101080

Authors: Kossi Efouako Soklou, Hamid Marzag, Béatrice Vallée, Sylvain Routier, Karen Plé

Institutions: Université d'Orléans, Centre National de la Recherche Scientifique, Institut de Chimie Organique et Analytique, Inserm, Centre de Biophysique Moléculaire

Language: English

Topic: Catalytic Alkyne Reactions

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

Open Access status: green

Funders: Agence Nationale de la Recherche, Ligue Contre le Cancer, Centre National de la Recherche Scientifique

Awards: G195474297, G2900821844, Radiopharmaceutiques Innovants en Oncologie et Neurologie, G7311628704, Synthèse Organique : des molécules au vivant