Total synthesis of (-)-nakadomarin A.
A short and highly stereoselective synthesis of (-)-nakadomarin A has been developed using combinations of catalyst-controlled bond formations, one-pot multistep procedures, and powerful route-shortening reaction cascades. Several unprecedented chemical transformations were developed, including a highly Z-selective, eight-membered-ring-forming intramolecular Julia-Kocienski reaction, a highly diastereoselective intramolecular furan/iminium ion cyclization, and a sulfonic acid-controlled Z-selective macrocyclic ring-closing metathesis. In conjunction with a diastereoselective nitro olefin Michael addition under bifunctional organocatalysis and a nitro-Mannich/lactamization cascade, these transformations allowed the construction of this architecturally complex natural product in significant quantities in 12 steps (longest linear sequence) from commercially available starting materials.
Jakubec
Pavol
P
Department of Chemistry, Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford OX1 3TA, UK.
Cockfield
Dane M
DM
Dixon
Darren J
DJ
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry; D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000737:chemistry; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry; D002243:Carbolines / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D013237:Stereoisomerism
D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D000970:Antineoplastic Agents; D002243:Carbolines; C476640:nakadomarin A