Total synthesis of a stereoisomer of bistramide C and assignment of configuration of the natural product.
After the isolation of the bioactive polyether bistramide C from the marine ascidian Lissoclinum bistratum in 1988, NMR spectroscopic investigations over the next 12 years reduced the total number of possible stereoisomers of this compound from 1024 to 32. Based on the preparation of segments of the natural product as well as the total synthesis of a randomly selected stereoisomer of bistramide C, the stereochemical puzzle could be further simplified to eight possible stereoisomers. A convergent three-segment coupling strategy, the use of a common, D-glucose-derived intermediate for the preparation of pyran rings in two segments, a stereoselective photo-spiroketalization, and the use of azides to minimize protective group manipulations before segment couplings are highlights of the synthetic approach. The total synthesis also provided the key segments for a chiroptical analysis according to van't Hoff's principle of optical superposition, which was crucial for the assignment of a sole relative and absolute configuration of the natural product. Bistramide C represents therefore the first member of this class of structurally unusual marine polyethers whose configuration is known as a result of the combined use of synthetic and chiroptical tools.
Wipf
Peter
P
Department of Chemistry, University of Pittsburgh Pittsburgh, PA 15260, USA. pwipf+@pitt.edu
Uto
Yoshikazu
Y
Yoshimura
Seiji
S
D000818:Animals; D004988:Ethers, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry*; D008968:Molecular Conformation; D015394:Molecular Structure; D013237:Stereoisomerism; D014561:Urochordata / Q000737:chemistry*
D004988:Ethers, Cyclic; C456580:bistramide C