Diversity-orientated synthesis of macrocyclic heterocycles using a double SNAr approach. Issue 28 (1st July 2021)

• Record Type: Journal Article
• Authors: Raubo, Piotr; Carbajo, Rodrigo J.; McCoull, William; Raubo, Joanna; Thomas, Morgan
• Is Part Of: Organic & biomolecular chemistry. Volume 19:Issue 28(2021)
• Page Start: 6274
• Page End: 6290
• Publication Date: 2021-07-01
• Subjects: Chemistry, Organic -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1039/d1ob00612f
• Languages: English
• ISSNs: 1477-0520

Abstract

Abstract : An efficient macrocyclisation approach based on the double aromatic nucleophilic substitution (SNACK) was developed. Abstract : An efficient macrocyclisation approach based on the double aromatic nucleophilic substitution (SNACK) was developed. This methodology allows a facile incorporation of heterocyclic motifs into macrocyclic rings and rapid synthesis of a significant number of structurally diverse macrocycles. SNACK macrocyclisation enables preparation of stable diastereoisomers of conformationally restricted macrocycles (atropisomers). Practical application of SNACK macrocyclisation in a drug discovery project was exemplified by the identification of high affinity macrocyclic binders of B-cell lymphoma 6 (BCL6).