Lactarius, metabolites

Sesquiterpenes, as already reported in the previous sections, are the most widespread Lactarius metabolites however, a few species possess a particular metabolism which leads to secondary metabolites of other classes. Moreover, interesting new compounds with a different biogenesis have been isolated also from species producing large quantities of sesquiterpenes. 

Further indirect support for this proposal has been provided by the recent demonstration that A -protoilludene (214) and compounds (215)— 220), belonging to some of the structural classes shown in Scheme 24, co-occur in the fungus Fomi-topsis insularia. Blennin A (221) and blennin B (222) have been identified as new metabolites of the inedible mushroom Lactarius blennius and a revised structure has been proposed for the co-metabolite, blennin C (223). An attempt to synthesize velleral (224) has provided a compound (225) which would seem to be... 

Sesquiterpenes and Other Secondary Metabolites of Genus Lactarius (Basidiomycetes) Chemistry and Biological Activity... 

In this review we will discuss the chemistry and biological aspects of those secondary metabolites that seem more peculiar to Lactarius than to other mushrooms and have, therefore, a taxonomic relevance. By contrast, other important metabolites, such as triterpenoids, sterols, polyisoprenoids, fatty acids, aminoacids, etc., widely distributed in several species of different... 

In Tables 1-23 the structures of isolated and synthetic compounds (the latter in italic) are reported, while Table 24 reports the distribution of secondary metabolites in the investigated Lactarius species, which have been listed according to the subdivision of the genus by M. Bon (2). In Table 24 the metabolites have the same number as in the previous Tables 1-23 and the references are reported in parentheses. 

Sesquiterpenes of several kinds are the characteristic metabolites isolated from Lactarius mushrooms. However, other metabolites such as alkaloids, phenols and derivatives have been found in some species. 

Drimane, farnesane, glutinopallane, protoilludane, isolactarane, and guaiane sesquiterpenes have been isolated so far in a few Lactarius species therefore, they may be considered chemotaxonomic markers. By contrast, large quantities of marasmane, lactarane and secolactarane metabolites occur in almost all Sections, as reported in Table 24. 

Recently, for the first time among the Lactarius sesquiterpenes, the protoilludane skeleton has been assigned to two metabolites of Lactarius violascens (23) (Table 5). Also this mushroom contains a sesquiterpene alcohol (5.1) and the corresponding 6-oxostearic acid ester 5.2. It is worth noting that this fatty acid (also named lactarinic acid) is peculiar to Lactarius mushrooms where it has been isolated in the form of many sesquiterpenoid esters. 

Occurrence of metabolites in Lactarius species and their biological significance... 

Fatty acid esters of metabolites different from sesquiterpenes have been isolated from intact fruiting bodies of particular Lactarius species the colourless phenol stearate 22.2 is a typical metabolite of L. fuliginosus and L. picinus (102), while L. lignyotus contains a mixture (22.7) of fatty acid esters of geranylgeranylhydroquinone (23). 

TABLE 24 - Occurrence of secondary metabolites in Lactarius species Sub-genus (Eu) Lactarius... 

Acknowledgements - We acknowledge the continuous financial support of our research project on mushroom metabolites by the Italian MURST (Funds 40%) and CNR (Progetto Finalizzato Chimica Fine 11). Most of the credit for our scientific contributions must be given to numerous coworkers whose names appear in the references. We wish also to remind our long friendship with W. M. Daniewski, B. Wickberg, O. Sterner, and the late M. Koc6r, who all have shared our passion for the Lactarius chemistry, and have collaborated with us for many years. 

Sesquiterpenoids are widespread metabolites of the Basidiomycetes. Lactarius species (milk or ink caps) are common Basidiomycetes that are found growing in woodlands. They are characterized by a latex which is exuded when the fruiting body is cut or broken. The colour and taste of the latex is of taxonomic significance. The latex of the edible species, Lactarius deliciosus, is at first carrot-coloured. On exposure to air it then darkens and turns a green-blue colour. The colour has been associated with the formation of an azulene, lac-taroviolin (5.55), which arises by the aerial oxidation of a dihydroazulene. 

The only natural product based on this ring system is necatorone 193. This alkaloid was isolated from a toadstool, Lactarius necator (84TL3575). This fungal metabolite showed a considerable mutagenic activity in the Ames test. A synthesis of necatorone 193 involving oxidative cyclization has been reported (Scheme 33) (85TL5975). 

Lactarorufin C (342) syn. isolactarorufin), a metabolite of the mushroom Lactarius rufus, has been assigned structure (342) on the basis of X-ray analysis of its p-bromobenzoate. The unusual carbon skeleton (341) of this compound may be biosynthesized by rearrangement of a tricyclic intermediate (340) derived from cyclohumulene (339). 

Drimenol (2) has also been used as a starting material for the preparation of uvidin C (26), a metabolite of fungus Lactarius uvidus Fries [29]. The eight-step synthesis was carried out according to Scheme 3 and includes oxidation of the diol (22) with m-chloroperbenzoic acid. The overall yield of (26) was 20% [28]. 

An investigation of the metabolites of Russula sardonia has resulted in the identification of three new vellerane sesquiterpenoids, furanether A (294), furosardosin A (295), and sardonialactone A (296). These compounds cooccur with a number of other known vellerane sesquiterpenoids which have been isolated previously from Lactarius species. Two related compounds, blennin A (297) and blennin D (298), have been isolated from Lactarius blennius ... 

Part 27. Biological Properties of Metabolites of Lactarius Origin. 157... 

Before this review was written four excellent reviews on fungal metabolites appeared in the literature (13-16). The last review comprised the literature concerning constituents of Lactarius up until the end of 1993. 

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