Total synthesis and structural revision of vannusals A and B: synthesis of the originally assigned structure of vannusal B.
The total synthesis of the originally assigned structure of vannusal B (2) and its diastereomer (d-2) are described. Initial forays into these structures with model systems revealed the viability of a metathesis-based approach and a SmI(2)-mediated strategy for the key cyclization to forge the central region of the molecule, ring C. The former approach was abandoned in favor of the latter when more functionalized substrates failed to enter the cyclization process. The successful, devised convergent strategy based on the SmI(2)-mediated ring closure utilized vinyl iodide (-)-26 and aldehyde fragment (+/-)-86 as key building blocks, whose lithium-mediated coupling led to isomeric coupling products (+)-87 and (-)-88 (as shown in Scheme 17 in the article). Intermediate (-)-88 was converted, via (-)-89 and (-)-90/(+)-91, to vannusal B structure 2 (as shown in Scheme 18 in the article), whose spectroscopic data did not match those reported for the natural product. Similarly, intermediate (+)-25, obtained through coupling of vinyl iodide (-)-26 and aldehyde (+/-)-27 (as shown in Scheme 13 in the article) was transformed via intermediates (-)-97 and (+)-98 (as shown in Scheme 19 in the article) to diastereomeric vannusal B structure (+)-d-2 (as shown in Scheme 19 in the article) which was also proven spectroscopically to be non-identical to the naturally occurring substance. These investigations led to the discovery and development of a number of new synthetic technologies that set the stage for the solution of the vannusal structural conundrum.
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
Dagneau
Philippe
P
Lanver
Andreas
A
Jennings
Michael P
MP
Arseniyadis
Stellios
S
Faraoni
Raffaella
R
Lizos
Dimitrios E
DE
D000447:Aldehydes / Q000737:chemistry; D003500:Cyclization; D007454:Iodides / Q000737:chemistry; D012493:Samarium / Q000737:chemistry; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000737:chemistry*; D013237:Stereoisomerism
D000447:Aldehydes; D007454:Iodides; D013141:Spiro Compounds; C513691:vannusal A; C543843:vannusal B; D012493:Samarium; C409809:samarium diiodide