Mould metabolites

Recent synthetic applications of the photochemical [2 + 2] cycloaddition of unsaturated sulfones have been noted. Musser and Fuchs84 have effected an intramolecular [2 + 2] addition of a 6-membered ring vinyl sulfone and a five-membered ring vinylogous ester in excellent yield, as part of a synthetic approach to the synthesis of the mould metabolite, cytochalasin C. The stereospecificity of the addition was only moderate, however, and later problems with this synthetic approach led to its abandonment. Williams and coworkers85 have used the facile [2 + 2] photoaddition of 73 and... 

Treatment of the diketone (35) with IN HC1 in MeOH gave the crystalline dimethylstipitatonate (36) which was the key intermediate in the total synthesis of the mould metabolite stipitotanic acid (37)16). 

A stereoselective total synthesis of the antifungal mould metabolite ( )-LL-Z1271a (165) from the readily available Wieland-Miescher diketone, via the keto-lactone (164), has been described. A synthesis of grindelic acid (167) from the unsaturated 7-toluene-p-sulphonate (166) utilized an intramolecular solvolysis of the toluene-p-sulphonate to construct the 9—13 ether bridge. 

Compounds which have an unsaturated y- or 5-lactone ring are reported to have carcinogenic and antitumour activity as well as other biological properties (72ABC2505). Many naturally occurring y-exo-enol lactones have been reported the mould metabolites... 

An autibiotio mould, metabolite from a species of Aspergillus was recently found by Sheehan and co-workers18 9 to incorporate an epoxide unit in its structure, which was formulated as (XVI). Another antibiotic from an Aspergillus species is the unusual bisepoxide fumagillin, whose structure waa recently established by Tarbell and co-workers to... 

The mould metabolite herqueinone 1 undergoes facile epimerisation at C-4 to give enantio-isoherqueinone when heated under reflux for one hour with anhydrous potassium carbonate in anhydrous acetone. 

Amone A, Cardillo R, Nasini B (1988) Secondary Mould Metabolites. XXIII. Isolation and Structure Elucidation of Melleolides I and J and Armellides A and B, Novel Sesquiterpe-noid Aryl Esters from Armillaria novae-zelandiae. Gazz Chim Ital 118 523... 

Mould Metabolites.—A second synthesis of deoxybrevianamide E has been reported 300 in essence, it is similar to the earlier synthesis,306 the major difference being simply the order in which the various stages are effected. Photochemical oxidation of deoxybrevianamide E (34a) provides the first satisfactory laboratory synthesis of brevianamide E (34b), which was obtained in 42% yield, together with its stereoisomer, the alternative cis-fused cyclization product. The stereochemistry depicted in (34b) rests on a comparison of the n.m.r. spectra of these two stereoisomers.300... 

Asterriquinone (12), a metabolite of Aspergillus terreus Strain IFO 6123, is simply 2,5-dihydroxybenzoquinone coupled to two isopentenylindole units.9 Unlike all previously known isopentenylindole mould metabolites, however, the reversed isopentenyl groups are attached, not to carbon atoms, but to the indolic nitrogen atom. 

Mould Metabolites.—The presence of pre-echinulin [L-alanyl-2 (l, 1-dimethyl-allyl)-L-tryptophan anhydride] in Aspergillus chevalieri has been confirmed,26 and two new metabolites, L-alanyl-L-tryptophan anhydride27" and D-valyl-L-tryptophan anhydride (30),276 have been isolated it is interesting to note that (30), unlike the other metabolites of this micro-organism, contains an amino-acid of the D series. 

This strategy has been used in the synthesis of the mould metabolite curvularin and its dimethyl ether derivative [146]. In the synthesis of curvularin (242) by Gerlach [146a], carboxylic acid 240 was exposed to a mixture of trifluoroacetic acid and its anhydride to give the macrocycle 241 via a Friedel-Crafts acylation. 

Mortlock A A, Jung EH.. Preparation of 4-(N-(5-pyrimidyl)amino) quinolines as inhibitors of aurora 2 kinase, in PCT Int.Appl. 2001, (AstraZeneca AB, Swed. Astrazeneca UK Limited). Wo. p. 62 pp. Aldridge DC, Armstrong JJ, Speake RN, Turner WB. The cy-tochalasins, a new class of biologicly active mould metabolites. Chem. Commun. 1967 1 26-27. 

At the dawn of the twentieth century, only a few simple fermentation products such as oxalic acid and citric acid had been isolated from the lower fungi. Soon after World War I, Harold Raistrick initiated the first systematic studies of the chemistry of mould metabolites and in the course of the following four decades made a seminal contribution to the recognition of fiingi as a major source of natural products. ... 

Mould Metabolites.—Intermediates on the presumed biosynthetic pathway from tryptophan to echinulin and its analogues continue to be isolated. The introduction of a reversed isoprene unit at C-2 leads to L-analyl-2-(l,l-dimethylallyl)-L-tryptophan anhydride (31), a compound which has already been synthesized, and which has now been shown to be a constituent of Aspergillus chevalieri (Mangin) Thom et Church IFO 4090. The dehydro-derivative, neoechinulin A (32), recently isolated from A. amstelodami, has now been shown to occur in A. ruber A... 

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. ... 

The antifungal mould metabolite siccanin (81) has been synthesized in nineteen steps.50 The asymmetric intramolecular Diels-Alder reaction of the magnesium salt of the amide (82) gives a predominance of the tricyclic diastereoisomer (83) which can be converted into the enantiomer (84) of naturally occurring farnesi-ferol C.51... 

A facile synthesis of cyclopentadienone epoxides via thermal rDA cycloreversion of a tricyclodece-none epoxide and its acetal derivatives has been applied to the preparation of cyclopentanoid antibiotics. - This procedure has been used in an efficient synthesis of terrein, a mould metabolite from Aspergillus terreus, by rDA synthesis of cyclopentadiene epoxide intermediate (57). FVP conditions for these reactions typically involve temperatures of 420-600 C. Furan-derived DA adducts have also been used to generate cyclopentadienone epoxides. The thermal rDA reaction of the furan-derived DA adduct (58) proceeds at temperatures as low as 330 °C with complete cycloreversion and generation of epoxide (59) in nearly quantitative yield (equation 32). Subsequent elaboration led to epipentenomycin derivatives such as (60). 

Fnsarinic acid is a mould metabolite with antibiotic and antihypertensive activity. Two syntheses of this substance employ cycloadditions, one" to produce a 1,5-diketone and the other to generate a 1 -dimethylamino-1,4-dihydropyridine. 

The relatively efficient cyclisation of monocyclofamesic acid with boron trifluoride etherate to methyl bicyclofarnesate (46) has led to a successful synthesis of drimenin (48) via acid-catalysed lactonisation of the allylic alcohol (47), a product of singlet oxygen addition to (46). It has also been shown that hydride reduction of drimenin to the allylic diol (49) followed by a two-step oxidation procedure yields cinnamolide (39). A Ci antifungal mould metabolite has... 

Complete details of the photochemically-based synthesis of -himachalene (151) have been reported by de Mayo et a/. The extensive chemistry associated with isolongifolene (153), an acid-catalysed rearrangement product of longifolene, is detailed in six papers by Dev and his collaborators. An elegant synthesis of the mould metabolite culmorin (154) has been described by Roberts, Poonian, and Welch. The basic building block in this synthesis was the bicyclic diketone... 

The dimeric mould metabolite ditryptophenaline (186) has been very simply synthesised, albeit in only 3% yield, by the oxidative dimerization of cyclo-L-N-methylphenylalanyl-L-tryptophan... 

Mould Metabolites.—In the search for later intermediates in the biosynthesis of echinulin and neochinulin three new prenylated indole derivatives have been isolated from the mycelium of Aspergillus amstelodami these are neoechinulin A (19), neoechinulin B (20), and neoechinulin C (cryptoechinulin A) (21). The isolation of neoechinulin A lends credence to the proposal that in the biosynthesis of echinulin the first isopentenyl group is introduced to position 2 of a preformed cyc/o-alanyltryptophan system, while the isolation of (19)—(21) suggests that neoechinulin (22) may be formed by a dehydrogenation followed by oxidative fission of the alanyl methyl group (CHMe —> C=CH2 C=0). ... 

Mould Metabolites Ergot Alkaloids Monoterpenoid Alkaloids... 

J. E.Saxton, Recent Progress in the Chemistry of Indole Alkaloids and Mould Metabolites, Nat.Prod.Rep., 1986, 3, 353. ... 

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