Borylation via iridium catalysed C-H activation: a new concise route to duocarmycin derivatives

• Published in: Organic & biomolecular chemistry Vol. 22; no. 27; pp. 5603 - 5607
• Main Authors: Cominetti, Marco M. D., Goddard, Zoe R., Hood, Bethany R., Beekman, Andrew M., O'Connell, Maria A., Searcey, Mark
• Format: Journal Article
• Language: English
• Published: CAMBRIDGE Royal Soc Chemistry 10.07.2024; Royal Society of Chemistry; The Royal Society of Chemistry
• Subjects: Alkylation; Boron Compounds - chemical synthesis; Boron Compounds - chemistry; Catalysis; Chemical reactions; Chemical synthesis; Chemistry; Chemistry, Organic; Duocarmycins; Ethyl esters; Indoles - chemical synthesis; Indoles - chemistry; Iridium; Iridium - chemistry; Molecular Structure; Physical Sciences; Pyrroles - chemical synthesis; Pyrroles - chemistry; Science & Technology; BORONIC ACIDS; 2-SUBSTITUTED INDOLES; DESIGN; ANALOGS; PRODRUGS; CYTOSTATIC CC-1065; SUBJECT
• ISSN: 1477-0520; 1477-0539; 1477-0539
• DOI: 10.1039/d4ob00814f

The synthesis of the ethyl ester analogue of the ultrapotent antitumour antibiotic seco-duocarmycin SA has been achieved in eleven linear steps from commercially available starting materials. The DSA alkylation subunit can be made in ten linear steps from the same precursor. The route involves C-H activation at the equivalent of the C7 position on indole leading to a borylated intermediate 9 that is stable enough for peptide coupling reactions but can be easily converted to the free hydroxyl analogue.