Penitrems

A more highly substituted analogue was successfully used in the preparation of the penitrem class of terpenoid indoles[3]. 

Several other twofold cyclization strategies have been developed by Smith and coworkers, ultimately to obtain access to the cyclic framework of penitrem D with the correct stereochemistry [176]. Williams group has been interested in Stemona alkaloids, which are represented by approximately 50 structurally novel, polycyclic natu-... 

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). 

Gonzalez MC, Lull C, Moya P, Ayala I, Primo J, Yufera EP (2003) Insecticidal Activity of Penitrems, Including Penitrem G, a New Member of the Family Isolated from Penicillium crustosum. J Agric Food Chem 51 2156... 

Six mycotoxins, penitrems A—F [(16a)—(16f)], derived from tryptophan (with loss of the side-chain) and a diterpene unit (with loss of a carbon atom), have been isolated from Penicillium crustosum iSe of these, penitrem A was first isolated15/in 1968 from P. cyclopium, and penitrems B and C in 197l15 from a micro-organism originally presumed to be P. palitans, but now classified as P. crustosum. The occurrence of penitrem A in P. cyclopium has recently been confirmed, and the presence of penitrem B was also demonstrated.156... 

The structures of the penitrems were elucidated156 mainly by extensive n.m.r. studies, both on the natural material and on 13C-enriched material isolated after administration of appropriate 13C-labelled precursors (tryptophan and acetate) to the cultures. Structure (16a) incorporates the proposed relative stereochemistry of penitrem A, but no deductions concerning the stereochemistry of the other metabolites were made. Penitrem A is a powerful toxin, and causes sustained tremors, disco-ordination, and convulsions in laboratory and farm animals. 

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). 

The mycotoxins with the greatest potential risk to human and animal health as food and feed contaminants are AFs, trichothecenes, fiimonisins, zearalenone, ochratoxin A, and ergot alkaloids.109 Other mycotoxins such as cyclopiazonic acid, sterigmatocystin, gliotoxin, citrinin, penitrems, patulin, fusarin C, penicillic acid, and PR... 

Phomopsin A (83 in Figure 18) was isolated from Phomopsis leptostromiformis as the hepatotoxic metabolite responsible for lupinosis, which is a disease in animals caused by ingestion of Lupinus species infected with the fungus.169 Penicillium species produce other significant mycotoxins such as penitrem A (84), PR toxin (85), and rubratoxin B (86).170 Fusarin C (87) and fusaproliferin (88) are known as mycotoxins produced by Fusarium... 

Figure 18 Structures of phomopsin A, penitrem A, PR toxin, rubratoxin B, fusarin C, and fusaproliferin.

Species of Penicillium fungi are rich sources of indole metabolites, such as thomitrem A 71 and thomitrem E 72, isolated from Penicillium crustosum <2002P979>. They are structurally similar to previously described penitrem derivatives <1996CHEC-II(2)207> but lack the characteristic penitrem 17(18)-ether linkage. 

Steyn PS Mycotoxins, general view, chemistry and structure. Toxicol Lett 1995 82 843-851. Yamaguchi T, Nozawa K, Hosoc T, Nakajima S, Kawai KL Indoloditerpenes related to tremorgenic mycotoxin penitrems, from Penicillium crustosum. Phytochemistry 1993 32 1177-1181. Penn J, Swift R, Wigley LJ, Mantle PG, Bilton JN, Sheppard RN Janthitrems B and C, two principal indole-diterpenoids produced by Penicillium janthinellum. Phytochemistry 1993 32 1431-1434. 

A second family of K -channels comprises the Ca -sensitive K -channels - there are three recognized currents of this type. One, the high-conductance Ca -activated K -channel (Ibkicx)) - also called maxi-K channel, or BK channel - is blocked by TEA, Ba, quinine, tubocurarine, charybdotoxin, iberiotoxin, noxiustoxin, soyasaponin and penitrem A. This channel shows voltage-dependence, and the open-state probability of this large conductance channel increases with a rise in [Ca ] over the range O.l-lOpM, and... 

The amino acid tryptophan is a precursor of several fungal metabolites that affect the central nervous system. We have already met it as a constituent of the ergot alkaloids. Roquefortine (9.25) is a metabolite of Penicillium roqueforti and P. camemberti, which are found on some cheeses. Roquefortine is one of a series of mycotoxins that affect the central nervous system and induce tremors. The more complex penitrems are tremorogenic neurotoxins that are produced by the P. crustosum series. They are biosynthesized from a tryptophan and a triterpene unit. 

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]. 

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