Sesquiterpenes Isolated from Lactarius

Sesquiterpenes of several types are the characteristic metabolites isolated from most Lactarius mushrooms. However, other metabolites such as alkaloids, phenols and derivatives have been found in some species and they are grouped in a separate chapter with other compounds. 

Sesquiterpenes with drimane, farnesane, glutinopallane, protoilludane, isolactarane, and guaiane skeletons have been isolated so far from a few Lactarius species therefore, they may be considered as chemotaxonomic markers. By contrast, large amounts of marasmanes. 

Identification of some species is a difficult task, appearing frequently in section Albati, and has caused contradictory reports on the presence of certain metabolites, e.g, isovelleral (6.2), vellerolactone (11.6), velleral (10.6). We have not attempted to revise the literature in this respect and report sources of compounds as published. 

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The aldehyde rubrocinctal A (7.4), the 12-carboxymethyl ester rubrocinctal B (7.16), and the corresponding 6-oxostearoyl esters 7.27 and 7.31 were isolated from Lactarius rubrocinctus Section Ichorati (2), (69). They are of special interest because they are, along with glutinopallal esters 8.2 and 8.3, the only examples of 12-oxygenated sesquiterpenes isolated from Lactarius species. 

The only two known natural glutinopallane sesquiterpenes (8.2,8.3) have been isolated from Lactarius glutinopallens (42) (Table 8). Their structures are strictly related to velutinal esters (7.14, 7.15) for the presence of the cyclopropane ring and the 7a,8a-epoxyde, and to rubrocinctals 7.7 and 7.8 for the carbomethoxy group at C-3. 

The fascinating lactone isolactarorufin (9.5) (Table 9) is the only example of isolactarane sesquiterpenes isolated from a Lactarius specie (43-45). The structure of isolactarorufin has been elucidated by spectroscopic data and confirmed by X-ray analysis of its p-bromobenzoate 9.8 (45). 

The fascinating lactone isolactarorufin (9.4), at first discovered in an EtOH extract of L. rufus (75, 76, 77) and later also in L. vellereus (5S) and L. necator, is the only known isolactarane sesquiterpene so far isolated from Lactarius species. Other compounds listed in Part 9 are synthetic derivatives that were prepared for structure elucidation of the parent compound or for investigation of their biological properties. 

Recently, the farnesane sesquiterpenes 1.1-1.9 (Table 1) have been isolated for the Brst time from Lactarius porninsis, the only species of the Section Zonarii investigated so far (8). Pominsal (1.1), porninsol (1.2) and the esters 1.3-1.9 show a high thermal and photochemical lability because of the conjugated tetraene system and readily polymerize when their solutions are taken to dryness. Therefore, special mild conditions are required for their isolation and for recording the spectroscopic data. The composition of the ester mixture 1.3-1.9 was established by capillary GC and GC-MS analysis of the methyl esters obtained by transesterification (8). 

Guaiane sesquiterpenes (Table 4) have been isolated so far only from Lactarius species of the Section Dapetes (Lactarius deliciosus, L. sanguifluus, etc.) which are characterized by the secretion of a strong coloured milky juice. Usually these mushrooms are edible and of pleasant taste. 

Other highly oxygenated bicyclic marasmane sesquiterpenes have been isolated from an EtOH extract of L. vellereus, which for many aspects seems an inexhaustible mine of Lactarius sesquiterpenes of any kind (see Table 24). The very unstable 5,10a,13-trihydroxymarasm-7(8)-ene (6.7) is accompanied by the 13-normarasmane isomers 6.12 and 6.13 (32) The latter ketones can derive from lactaropallidine (6.6) by (J-elimination and oxidation at C-7. 

New sesquiterpenes of the lactarane (occasionally named also vellerane) group (Table 10) have been isolated by Swedish authors during their pioneering work on the chemical defence system of Lactarius species. Vellerol (10.8) and vellerdiol (10.20) were first isolated from extracts of Lactarius vellereus made at different times after grinding the mushrooms (27). The reduction of either... 

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). 

Pang, Z., F. Bocchio, and O. Sterner The Isolation of New Sesquiterpene Aldehydes from Injured Fruit Bodies of Lactarius scrobiculatus. Tetrahedron Letters, 33, 6863 (1992). 

Daniewski, W.M., and M. Kocor Isolation and Structure of Some New Sesquiterpenes from Lactarius rufus. Bull. Acad. Polon. Sci., Ser. Sci, Chim., 18, 585 (1970). 

Daniewski, W.M., P.A. Grieco, J. Huffman, A. Rymkiewicz, and A. Wawrzun, 1981. Isolation of 12-hydroxy-caryophyllene-4,5-oxide, a sesquiterpene from Lactarius camphoratus. Ph tochemis 20 2733-2734. 

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. 

Three sesquiterpenes (14.1, 14.2, and 14.3) of this group are considered genuine metabolites of Lactarius and blennin C (14.3) is apparently one of the most frequently isolated. The structure initially assigned to blennin C had the lactone carbonyl at C-13 (50, 99), but was later revised to 14.3 on the basis of chemical and spectroscopic evidence 103). Lactardial (14.2), formally a 1,4-dialdehyde possessing a pungent taste and antimicrobial activity, is formed from velutinal esters (7.28 and 7.30) both through enzymatic and chemical routes (72). 

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