Jatrophatrione

Entry 8 was used to create the central nine-membered ring system found in the diterpene jatrophatrione. Entry 9 is an example of a boronate fragmentation (see p. 899). Entry 10 illustrates enolate fragmentation. The reaction presumably proceeds... 

Leo Paquette of Ohio State recently reported (J. Am. Chem. Soc. 125 1567, 2003) the total synthesis of jatrophatrione 1 and citlalitrione 2. These diterpenes, which share a central highly-subsituted 5-9-5 core, show remarkable tumor-inhibitory activity. 

Ir Catalyst, ester aldol condensation, enantioselective 6 Jatrophatrione synthesis 24... 

TOTAL SYNTHESIS OF JATROPHATRIONE, AN UNPRECEDENTED [5.9.5] TRICYCLIC ANTILEUKEMIC DITERPENE... 

Although the spectroscopic dilemma described above may be classified as minor by some, our perfectionist tendencies prompted us to seek a companion source of structural confirmation. Our search for natural products closely related in structure to 1 was rewarded by the discovery of a report that appeared in 1988 concerning the identification of constituents obtained by extraction of the roots of tlapelex path . This plant is native to northeastern Mexico and the name is Aztec for Jatropha dioica The natives of this region appear to have recognized for some time its beneficial effects in the treatment of skin cancer. The Texas A+M University team headed by Ian Scott determined by spectroscopic means and X-ray crystal structure analysis that the major active constituent of J. dioica is citlalitrione (111). In essence, 111 constitutes a monoepoxide of jatrophatrione. 

L.A. Paquette and co-workers accomplished the first total synthesis of the antileukemic agent jatrophatrione. " This natural product has a [5.9.5] fused tricyclic skeleton with a trans-BIC ring fusion. The key step in their approach was the Grab fragmentation to obtain the tricyclo[5.9.5] skeleton. The tetracyclic 1,3-diol was monomesylated on the less hindered hydroxyl group and then treated with potassium fert-butoxide, triggering the concerted fragmentation to afford the desired tricyclic product in almost quantitative yield. 

After considerable experimentation, a similar hydrosilylation protocol was used as a key step for the syntheses of jatrophatrione and citlalitrione by Paquette and co-workers.32 Following the stereoselective reduction of a tricyclic ketone with lithium aluminum hydride to provide alochol 28, silylation and platinum catalyzed hydrosilylation were effected to produce 29. Finally, the carbon-silicon bond was successfully cleaved to generate diol 30 in an impressive 93% yield. 

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