Dysidiolides

In a lolal syntliesis of cdc25.A ptolein phosphatase inbibdot dysidiolide i46) [37], substilulion on an sp- carbon center by vinyl cuprate was used lo accom-... 

An illustrative example of an alternative strategy (cf Fig. 11c) involving the use of a novel traceless linker is found in the multistep synthesis of 6-epi-dysidiolide (363) and several dysidiolide-derived phosphatase inhibitors by Waldmann and coworkers [153], outlined in Scheme 70. During the synthesis, the growing skeleton of 363 remained attached to a robust dienic linker. After completion of intermediate 362, the terminal olefin in 363 was liberated from the solid support by the final metathesis process with concomitant formation of a polymer-bound cyclopentene 364. Notably, during the synthesis it turned out that polymer-bound intermediate 365a, in contrast to soluble benzoate 365b, produced diene 367 only in low yield. After introduction of an additional linker (cf intermediate 366), diene 367 was released in distinctly improved yield by RCM. 

Scheme 70 Traceless removal of polymer 364 by RCM in the synthesis of 6-epi-dysidiolide (363) [153]...

This reaction has been used to construct the carbon skeleton found in dysidiolide, a cell cycle inhibitor isolated from a marine sponge.73 In this case, the reactive oxonium ion intermediate was generated by O-silylation. 

In an approach by Jung and Nishimura, the assembly of the dysidiolide decalin skeleton 54 was deemed possible via an intermolecular Diels-Alder reaction between cydohexene 52 and dienophile 53 [14]. Based on precedent established by Wulff et al. [15] [where Z = C(OCH3)=Cr(CO)5], the cycloaddition should give predominantly the exo isomer as shown (Scheme 19.12). However, all attempts to effect the cydoad-dition simply gave recovery of starting material. It was reasoned that steric hindrance was to blame. The steric hindrance assodated with the dienophile was decreased by replacing one of the methyl groups with another double bond in the... 

Figure 10. Analogs of the naturally occurring Cdc25A inhibitor dysidiolide screened for binding to the PSSC member enzymes Cdc25A, AChE and 11 pHSDVz (IC50 values are given).

Corey, E.J. Roberts, B.E. (1997B) Total synthesis of dysidiolide. J. Am. Chem. Soc., 119, 12425-31. Corey, E.J. Lazerwith, S.E. (1998) A direct and efficient streocontrolled synthetic route to the pseudopterosins, potent marine anti-inflammatojy agents. J. Am. Chem. Soc., 120, 12777-82. 

Gunasekera, S.P. McCarthy, P.J. Kelly-Borges, M. Lobkovsky, E. Clardy, J. (1996A) Dysidiolide a novel protein phosphatase inhibitor from the Caribbean sponge Dysidea etheria. J. Am. Chem. Soc., 118, 8759-60. 

Takahashi, M. Dodo, K. Hashimoto, Y. Shirai, R. (2000) Concise asymmetric synthesis of dysidiolide. Tetrahedron. Lett., 41, 2111-4. 

An illustrative example for the alternative strategy, (cf Figure 7c) by the use of a traceless linker, is found in the multi-step synthesis of 6- f-dysidiolide 434 and several dysidiolide-derived phosphatase inhibitors by Waldmann and co-workers outlined in Scheme 83. During the synthesis, the growing skeleton of 434 remained attached... 

This compound also showed antispasmodic activity [122], A variety of cytotoxic compounds was isolated, including a bishomosesterterpene and dysidiolide from another Dysideci sp., a sulfated sesterterpene hydroquinone from a Hippospongia sp., and two new sesterterpenes, lintenolides F and G from the Caribbean sponge Cacospongia linteiformis [123,124],... 

However, the formation of dysidiolide (1) requires the regiospecific removal of the hydrogen at C-l on the endoperoxide 31. This is achieved by treatment with a hindered base such as diisopropylethylamine (Hunig s base) at low temperature in order to favor base-catalyzed decomposition rather than thermal decomposition. 

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