Studies toward diazonamide A: development of a hetero-pinacol macrocyclization cascade for the construction of the bis-macrocyclic framework of the originally proposed structure.
In this article, we describe further studies toward the originally proposed structure of diazonamide A (1). After confronting a number of failures in synthesizing the heterocyclic core of that structure, success was finally realized through the development of a novel hetero-pinacol-based macrocyclization cascade sequence. Subsequent elaboration led to an advanced compound bearing both of the 12-membered rings of the target molecule. In addition, preliminary biological studies with intermediates and simplified analogues obtained via the developed sequences are also described.
Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA. kcn@scripps.edu
K C
KC
Nicolaou
Scott A
SA
Snyder
Nicolas
N
Giuseppone
Xianhai
X
Huang
Marco
M
Bella
Mali V
MV
Reddy
Paraselli Bheema
PB
Rao
Alexandros E
AE
Koumbis
Aurora
A
O'Brate
Paraskevi
P
Giannakakou
D003500:Cyclization; D006576:Heterocyclic Compounds, 4 or More Rings / Q000138:chemical synthesis* / Q000737:chemistry; D010080:Oxazoles / Q000138:chemical synthesis* / Q000737:chemistry; D013329:Structure-Activity Relationship
D006576:Heterocyclic Compounds, 4 or More Rings; D010080:Oxazoles; C408862:diazonamide A