Penitrem indole alkaloids

Curran described an efficient, approach to the BCD ring system of the penitrem indole alkaloids that exploits a Sml2-mediated radical-anionic sequence.11 Treatment of iodide 17 with Sml2 and HMPA gave 18, the product of radical cyclisation-intermolecular Barbier addition, in satisfactory yield (Scheme 6.6). 

Ca2+ channels are inhibited by several bis-isoquinoline alkaloids (e.g., berbamine, hernandezine, liensinine, monterine, tetrandine), aporphines (e.g., glaucine, norushinsunine), complex indole alkaloids (bis-nortoxiferine, hirsutine, mitragynine, paspaline, paspalitrem, paxilline, penitrem), or other bulky alkaloids (agelasine, contotoxins, crambescidin, ryanodine). Many channel blocker occur in animal venoms it has been estimated that 10% of marine natural products have these properties [65]. 

Indole-alkaloid isoprenoid was isolated from extracts of Penicillium crustosum grown on rice. This compound, designated thomitrem (53), contains a 18(19)-double bond and lacks the characteristic penitrem 17(18)-ether linkage [100],... 

In 1983, de Jesus and coworkers isolated tremorogenic mycotoxins named penitrems A (96), B (99), C (100), D (101), E (97), and F (102) from Penicillium cructosum [73, 75]. Penitrems and related compounds are shown in Fig. (17). Penitrems are indole alkaloids combined with... 

Smith AB III, Haseltine JN, Visnick M (1989) Tremorgenic indole alkaloid studies. 6. Preparation of an advanced intermediate for the synthesis of penitrem D. Synthesis of an indole-oxocane. Tetrahedron 45 2431-2449... 

Isoprenoids (isopentenoids). The name for a group of natural products made up of isoprene units (e.g., ses-qui-, di-, and triterpenes, iridoids, carotinoids, steroids, natural rubber, etc.). Many non-isoprenoid compounds, however, do possess isoprenoid side chains, e.g., tocopherols, ubiquinones, chlorophyll, or contain isoprenoid structures incorporated into their skeletons, e.g., monoterpenoid indole alkaloids, penitrems, Cinchona alkaloids. 

A new halogen-containing member of the penitrem family of indole-diterpe-noids, which have insecticidal activity (1397), is thomitrem A (1466) from Penicil-lium crustosum (1398). The novel dichlorinated calmodulin inhibitor, malbrancheamide (1467), was characterized from the fungus Malbranchea auran-tiaca (1399). The microbe Streptomyces rugosporus produces pyrroindomycin B (1468), which is active against both methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococci (1400). The Chinese shrub Acacia confusa has yielded the unusual chlorotryptamine alkaloid 1469, which does not appear to be an artifactual dichloromethane adduct (1401). 

The key indole-forming step for each of Smith s alkaloid syntheses is shown in Scheme 2. For the synthesis of a model indole related to penitrem D, indole 2 was an advanced intermediate (equation 1) [3]. Likewise, indole 3 was synthesized as a molecule that will soon embody the A, F, and I rings of penitrem D (equation 2) [4], and indole... 

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