Nodulisporic acid

Magnus, P. Mansl, T.E. (1999) Synthesis of the ABCD-rings ofthe insecticidal indole alkaloid nodulisporic acid. Tetrahedrcm Lett., 40,6909-12. 

Later in 1997, Ondeyka et a/.83 reported the isolation and identification of the structure of nodulisporic acid (27) using micro-NMR probe technology. Nod-ulisporic acid is a novel insecticide from Nodulisporium sp. and was the first representative of a new class of indole terpenes to be identified. The authors used a combination of -detected homo- and heteronuclear 2D-NMR experiments to assemble the structure in conjunction with a series of three INADEQUATE, each 5 days long, optimized from 40 to 60 Hz that employed a 26 mg sample of 27. The INADEQUATE data were subjected to computer analysis,84 86 which identified 32 of 47 possible 13C-13C connectivities. 

Interestingly, the authors also used micro-NMR capabilities to elucidate the structures of two degradation products of nodulisporic acid (28). 

Spinosyns were discovered from the fermentation broth of Saccharopolyspora spinosa by screening for mortality of blowfly larvae, and a mixture of spinosyns A (116) and D (117) was approved and used successfully as a crop protection and an antiparasitic animal health agent. (151) Nodulisporic acids are an indole diterpenoid class discovered from various species of Nodulisporium as orally active antiflea and antitick agents for dogs and cats (152, 153). The most active of the series is... 

JD, Ostlind DA, Tsou NN, Ball RG, Singh SB. Nodulisporic Acid A, a novel and potent insecticide from a nodulisporium sp. Isolation, structure determination, and chemical transformations. J. Am. Chem. Soc. 1997 119 8809-8816. 

Byme KM, Smith SK, Ondeyka JG. Biosynthesis of nodulisporic acid A precursor studies. J Am Chem Soc 124 7055-7060, 2002. 

Merck chemists found BrCCls/DBU to be the preferred method for preparing 2"-oxazole analogs of nodulisporic acid 1591, which were evaluated as potential vetinary antiflea and antitick agents (Scheme 1.405). 

DmGluCla, but not Rdl, exists in the Drosophila nervous system and binds aver-mectin but not nodulisporic acid, both of which are allosteric activators of GluCls. Another population, assembled from both DmGluCla and Rdl subunits and binding both avermectin and nodulisporic acid, also exists in the Drosophila nervous system, but coexpression of DmGluCla and Rdl in the Xenopus oocyte expression system does not yield functional heteromultimers, indicating that other subunits may be needed [54]. 

A more recent example illustrates the continuing applicability of this transformation in natural product synthesis, in this case toward 20, which bears a core resembling that of insecticidal indole diterpene nodulisporic acid... 

---