Total synthesis and structural revision of vannusals A and B: synthesis of the true structures of vannusals A and B.
Having determined through total synthesis that the originally assigned structure of vannusals A and B were incorrect, we set out to uncover the identity of the true structures of these novel marine natural products. Our search was based on intelligence gathered by NMR spectroscopy and chemical synthesis and took us through the total synthesis of eight diastereomeric vannusal B structures [2, d-2, 3, d-3, 4, d-4, 5, and d-5, Figure 2]. The true structures of vannusals A and B were finally determined to be d-5 and d-1, respectively. Their total synthesis was based on a highly convergent and efficient strategy that involved fragments vinyl iodide (-)-6 and aldehyde (+/-)-94, and featured a stereoselective lithium-mediated coupling reaction and a samarium-induced cyclization process that forged the final ring of the carbon framework. The synthetic strategies and technologies developed in these investigations expand the scope of chemical synthesis and render these compounds readily available for biological evaluation, while the NMR spectroscopic insights gained should prove useful in future structural determination endeavors.
Nicolaou
K C
KC
Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA. kcn@scripps.edu
Ortiz
Adrian
A
Zhang
Hongjun
H
Guella
Graziano
G
D018360:Crystallography, X-Ray; D009682:Magnetic Resonance Spectroscopy; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000737:chemistry*; D013237:Stereoisomerism
D013141:Spiro Compounds; C513691:vannusal A; C543843:vannusal B