Indole-diterpenes

The Gassman method has proven to be adaptable to complex structures, such as the intermediate 7.20B used in the synthesis of the indole diterpenes paspalicine and pasalinine[5]. Table 7.5 gives some other examples. 

Introduction of the cyclopropane moiety with the correct stereochemistry in the cyclopen tenone subunit was successful in creating an angular methyl group at the C/D junction of the trans-hydrindane ring system of paspalicine, an indole diterpene mould metabolite. ... 

Garcia ML, Giacobbe RA, Hensens OD, Lee SH, McManus OB, Zink DL. Indole diterpene alkaloid compounds. U.S. Patent 5,541,208, 1996. 

Young C, McMillan L, Telfer E, Scott B. Molecular cloning and genetic analysis of an indole-diterpene gene cluster from Penicillium paxilli. Mol Microbiol 39 754-764, 2001. 

MOLECULAR CLONING OF INDOLE-DITERPENE BIOSYNTHESIS GENES... 

The mode of action of the tremorgenic indole-diterpenes is not well understood, but pharmacological studies suggest that they interfere with neurotransmitter release. They are potent inhibitors of high-conductance Ca +-activated K" " (maxi-K) channels and have also been shown to modulate the Y-aminobutyric acid-gated ion channel [250, 251]. 

Subsequently, the intact incorporation of multiply H-labeled 3-geranylgeranylind ole 49b into paxilline proved that 3-geranylgeranylindole is a biosynthetic intermediate of indole-diterpenes (Figure 5.59) [256]. Thus, the proposal for the early steps of paxilline biosynthesis involves the formation of 3-geranylgeranylindole 49a catalyzed by GGPP synthase, subsequent epoxidation, and cationic cyclization to produce emindole SB. 

Gloer JB, Rinderknecht BL, Wicklow DT, Dowd PF (1989) Nominine - a New Insecticidal Indole Diterpene from the Sclerotia of Aspergillus nomius. J Org Chem 54 2530... 

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... 

In 1992, Smith and his group described the total synthesis of indole diterpenes (+)-paspalicine and (+)-paspalinine based on the use of Sommelet-Hauser reaction for the formation of the polycyclic indole... 

Tubingensins A (20) and B (21) are considered to arise from indolic diterpenes such as nominine (191) which occur in related species of Aspergillus. 

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