Annonaceous acetogenins

Interchanging the order of the CM and TST-RCM reactions allows for the preferential functionalization of the less hindered and more reactive Type I alkene and thus permits the formation of the seven-membered silaketal without competitive RCM. A critical feature for the success of this strategy is that the formation of the cis-silaketal is preferred over the trans-derivative, which provides optimal rates of reaction [22]. Treatment of a mixture of the unsymmetrical bis-alkoxysilane 58 and butenolide 60 (1 4 ratio) with catalyst [Ru]-III provided the gigantecin skeleton 62 in 63% yield in a single step. Additionally, the formation of the homodimer of butenolide 60 is inconsequential since it can be recycled through 

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Feras QA, Lingling R, Yan Z, McLaughlin JL. Unusual bioactive annonaceous acetogenins from Goniothalamus giganteus. Tetrahedron 1998 54 5833-5844. 

Solanaceae), acts as competitive inhibitor for ubiquinone in Complex I. Methyl capsaicin is more potent than capsaicin, indicating that the phenolic OH is not essential for the activity [297]. Other natural inhibitors of Complex I are annonaceous acetogenins. These compounds belong to a wide group of natural products isolated from several species of the Annonaceae family, which include more than 250 molecules with diverse chemical structures. Among the various classes, it seems that monotetrahydrofuranic derivatives are less potent than other acetogenins [296, 299]. 

Thwarting Resistance Annonaceous Acetogenins as New Pesticidal and Antitumor Agents... 

The Annonaceous acetogenins are an important new group of long-chain fatty acid derivatives found exclusively in the plant family, Annonaceae. Nearly 400 compounds from this... 

Proposed biosynthetic pathways for selected representatives of the three main classes of acetogenins. (Adapted from Zeng, L. et al., Recent advances in Annonaceous acetogenins, Nat. Prod. Rep., 13, 275-306, 1996.)... 

The Annonaceous acetogenins offer a unique mode of action (ATP depletion) against MDR tumors and against insecticide-resistant pests and are predicted to become important future means of thwarting ATP-depleting-resistance mechanisms. Their SARs in several systems have been determined (Landolt et al., 1995 Alfonso et al., 1996 He et al., 1997 Oberlies et al., 1997 Miyoshi et al., 1998) and optimum structural features generally point to the bis-adjacent THF compounds such as bullatacin (1) and asimicin (2). 

Ahammadsahib, K.I., Hollingworth, R.M., McGovren, P.J., Hui, Y.-H., and McLaughlin, J.L. Inhibition of NADH ubiquinone reductase (mitochondrial complex I) by bullatacin, a potent antitumor and pesticidal Annonaceous acetogenin. Life Sci., 53, 1113, 1993. 

Alali, F.Q., Kaakeh, W., Bennett, G.W., and McLaughlin, J.L. Annonaceous acetogenins as natural pesticides potent toxicity against insecticide susceptible and resistant German cockroaches (Dictypotera Blattellidae).. Econ. Entomol., 91, 641, 1998a. 

Gu, Z.-M., Zhao, G.-X., Oberlies, N.H., Zeng, L., and McLaughlin, J.L. Annonaceous acetogenins potent mitochondrial inhibitors with diverse applications, In Recent Advances in Phytochemistry, Arnason, J.T. and Mata, R., Eds., Plenum Press, New York, 249-310, 1995. 

Gu, Z.-M., Zhou, D., Lewis, N.J., Wu, J., Johnson, H. A., McLaughlin, J.L., and Gordon, J. Quantitative evaluation of Annonaceous acetogenins in monthly samples of paw paw (Asimina triloba) twigs by liquid chromatography/electrospray ionization/tandem mass spectrometry. Phytochem. Anal., 10, 32, 1999. 

Oberlies, N.H., Chang, C.-J., and McLaughlin, J.L. Structure activity relationships of diverse Annonaceous acetogenins against multidrug resistant human mammary adenocarcinoma (MCF-7/Adr).. Med. Chem., 40, 2102, 1997a. 

Ratnayake, S., Rupprecht, J.K., Potter, W.M., and McLaughlin, J.L. Evaluation of various parts of the paw paw tree, Asimina triloba (Annonaceae) as commercial sources of the pesticidal Annonaceous acetogenins. /. Econ. Entomol., 85, 2353, 1992. 

McLaughlin, J.L, Annonaceous Acetogenins Antitumor and Pesticidal Principles of tile Paw Paw Tree, Abstract—Purdue University Chromatography Workshop 95,... 

A synthesis of the Annonaceous acetogenin asimicin and a side-chain analogue has been achieved by a highly convergent route in which Grubbs cross-metathesis played a key role.98... 

Co(modp)2 338a, oxygen, terf-butyl hydroperoxide, and isopropanol to 2-hydroxymethyltetrahydrofurans 419 in 53-79% yield with exclusive trans-selectivity [442]. Reduced tetrahydrofurans 420 were isolated as a side product. This method was applied in total syntheses of annonaceous acetogenins [443], such as gigantetrocin A [444, 445], asimilobin [446, 447], mucocin [448, 449], or bullatacin [450], as well as of the algal natural product aplysiallene [451]. 

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