Jatrophone

Scheme 35. The Stille reaction in Wiemer and Han s synthesis of (+)-jatrophone (135).

Alkyl halides possessing / -hydrogens are usually poor substrates for carbonylative cross-coupling due to competitive / -hydride elimination/ Allyl chlorides can be used in carbonylative cross-coupling with allylstannanes/ phenyl-, 3-furyl, or vinylstannanes " to afford allylketones in modest to good yields. Divinylketones can be accessed through the reaction of vinylstannanes with vinyl iodides or vinyl triflates, with the latter requiring the addition of LiCl. Synthetic potential of this method has been proved in the formation of macrocyclic ketone jatrophone. In the reaction of vinyl triflates with tetramethyltin or aryltrimethylstannanes the additional activation by ZnCle is required. 

N.A. Jutrophine, emetic, purgative oil, diterpene jatrophone, isovitexin, resins, isophytosterol, tannin, cyanidin, apigenin, histamine.145-146 This herb is toxic. A folk remedy for cancer. Treat asthma, constipation, diabetes, diarrhea. It is a disinfectant, laxative. Externally applied to piles and bums. 

When subjected to the action of propanethiol under basic conditions (pH 9.2), jatrophone (2) undergoes a Michael reaction across its C8-C9 double bond, followed by facile transannular cyclization to give the tetracyclic diketone 3.2,9 The susceptibility of this enone part structure to conjugate addition has been proposed to constitute the event responsible for the pronounced biological activity of 2.9... 

Carbonylative coupling of vinyl triflates with organotins (12, 470-471).3 The final step in a synthesis of the macrocyclic diterpene jatrophone (2) was effected by carbonylative coupling of a vinyl triflate with vinyltin catalyzed by bis(acetonitrile)-dichloropalladium. 

Jatrophanes (C5 C12) are cytotoxic, antitumour compounds from Jatropha species (Euphorbiaceae). Jatrophone binds to DNA and also has activity as a glutamate receptor antagonist. 

Jatrophone Jatropha elliptica, J. gossypiifolia Glu-R (DJNA) [antitumour,... 

Phorbol and its Relatives.—Jatrophone (114) is a macrocyclic diterpenoid tumour-inhibitor which has been isolated from Jatropha gossypiifolia (Euphorbiaceae). The structure was proven by Z-ray analysis of a cyclization product obtained with HBr in glacial acetic acid. Bertyadional (115) has been isolated from a Bertya species n.m.r. studies defined a large fragment of the molecule. The trienedione, which was reduced with zinc and acetic acid, underwent an isomerization in hot aqueous pyridine in which the 4(10) double bond was shifted to the 1(2) position. 

Various examples of use of alkenyltin/vinyl iodide couplings in natural-product synthesis have been provided Evans and Black [33] have obtained the macrolide insecticide (+)-A83 453A [(+)-lepicidin A] (Scheme 4-7), Burke et al. the ionophore antibiotic X-14547A [34] (Scheme 4-8), Kende et al. [35] lankacidin C (Scheme 4-9), while Han and Wiemer [36] have used the combination alkenyltin/vinyl triflate in the total synthesis of (+)-jatrophone. 

In the laboratory of L.S. Hegedus, the total synthesis of (+)-ep/-jatrophone was accomplished using a palladium-catalyzed carbonylative coupling as the key step. In the endgame of the synthesis, a 3-hydroxy ketone moiety was oxidized in excellent yield to the corresponding 1,3-dione using the mild Corey-Kim protocol. 

Gyorkos, A. C., Stille, J. K., Hegedus, L. S. The total synthesis of ( )-epi-jatrophone and ( )-jatrophone using palladium-catalyzed carbonylative coupling of vinyl triflates with vinyl stannanes as the macrocycle-forming step. J. Am. Chem. Soc. 1990,112, 8465-8472. 

Lewis acid catalyzed intramolecular alkylations of silyl enol ethers containing 5n1-reactive functionality provide useful routes to a variety of carbocyclic systems. - Smith et al have employed an intramolecular Mukaiyama reaction of the enol derivative (76) to produce the tetracyclic system (77) (equation 7). This transformation was a key step in their elegant synthesis of jatrophone. The synthesis... 

Equation 12.59 shows an intramolecular cross-coupling combined with a carbonylation, which was used in the synthesis of ( )-ep/-jatrophone (47), a diter-pene that possesses antitumor activity.126 Early in investigations on the reactivity... 

Below I outline briefly some recent findings in my laboratory in a program directed at tumor inhibitors of plant origin. This program, which has already led to the isolation of the active principles of more than 80 tumor-inhibitory extracts, has been the subject of two recent reviews (22). For this discussion of the future of plant-derived drugs, the stories of vernolepin and jatrophone will exemplify one important approach. 

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