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Total Synthesis of Sarcodictyins A and B
journal contribution
posted on 1998-08-13, 00:00 authored by K. C. Nicolaou, J. Y. Xu, S. Kim, J. Pfefferkorn, T. Ohshima, D. Vourloumis, S. HosokawaThe total synthesis of cytotoxic marine natural products possessing tubulin polymerization and
microtubule stabilization properties, sarcodictyins A (7) and B (8), is described. Two related approaches to
these target molecules have been developed, both utilizing (+)-carvone (9) as starting material. The first
approach involves a stereoselective construction of acetylenic aldehyde 27 (Scheme ) while the second approach
proceeds through a more direct but less selective sequence to the similar intermediate 36 (Scheme ). Both
strategies involve ring closures of the acetylenic aldehyde precursors to 10-membered rings under basic
conditions followed by elaboration and selective reduction of the acetylenic linkage to a cis double bond.
This promotes bridging to form the required tricyclic skeleton of the sarcodictyins (27 → 37 → 38 → 39 →
4, Scheme and 37 → 44 → 45 → 46 → 47 → 42, Scheme ) and (36 → 48 → 45, Scheme ). Installation
of the (E)-N(6‘)-methylurocanic acid residue was achieved by esterification with mixed anhydride 52, while
the C-3 ester moieties were installed by standard deprotection, oxidation, and esterification procedures.
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sarcodictyinanhydride 52Total Synthesistricyclic skeletonacetylenic aldehyde 27acetylenic linkagering closuresesterification procedurescytotoxic marinetubulin polymerizationtarget moleculesSchememicrotubule stabilization propertiesacetylenic aldehyde precursorsstereoselective constructionapproach proceeds
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