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.
Nicolaou
K C
KC
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
Snyder
Scott A
SA
Giuseppone
Nicolas
N
Huang
Xianhai
X
Bella
Marco
M
Reddy
Mali V
MV
Rao
Paraselli Bheema
PB
Koumbis
Alexandros E
AE
O'Brate
Aurora
A
Giannakakou
Paraskevi
P
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