Sesquiterpenes of Lactarius

The discussion of the chemistry of sesquiterpenes of Lactarius will comprise the following aspects  

In the following schemes some carbon skeletons are drawn in a manner different from that used so far in this review, because they have been taken directly from the cited articles and the present authors did not wish to introduce changes. 

Because of space limitations, standard reactions of Lactarius sesquiterpenes will not be described when usual reagents were employed and the outcome of the reactions was unexceptional. It must be said, however, that preparation of simple derivatives of sesquiterpenes of Lactarius was often an essential part of the work of structure elucidation. In several instances, for example, crystalline compounds suitable for X-ray analysis were produced. In addition, many semisynthetic derivatives often showed better biological activities than the natural products. Important synthetic derivatives are included in Parts 1 -20. 

This novel thermal rearrangement was also extended to the conversion of 9-hydroxyisovelleral (6.3) into its stereoisomer (6.11), and of isovellerol (7.11) into its isomarasmane stereoisomer (59). Other interesting thermal rearrangements were exhibited by vellerolactone (11.6) and the isomeric lactone 16.4 (81, 96). In both compounds, in their 

Vellerol (10.9) as well as isovellerol (7.11), piperalol (10.16), and e/7/-piperalol (10.17) readily dimerized in reagent grade solvents where traces of acid are probably present (7), 38). 

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The sesquiterpenes of Lactarius vellereus and their role in a proposed chemical defense system, O. Sterner, R. Bergman, J. Kihlberg and B. Wickberg, J. Nat. Prod., 1985, 48, 279. 

Sesquiterpenes of Lactarius origin, anti-feedant structure activity relationships, W.M. Daniewski, M. Gumulka, D. Przesmycka, K. Praszynska, E. Bloszyk and B. Drozda, Phytochemistry, 1995, 38, 1161. 

Among drimane sesquiterpenes of Lactarius, only uvidin C (3.9) has been chosen so far as a synthetic target. Two syntheses of this compound have been reported as a racemate by Ziegler et al. 148), and as the natural (—)-enantiomer by Cortes and colleagues 149),... 

Bergendorff, O., and O. Sterner The Sesquiterpenes of Lactarius deliciosus and Lactarius deterrimus. Phytochemistry, 27, 97 (1988). 

Daniewski, W.M., M. Gumulka, P. Gluzinski, J. Krajewski, E. Pankowska, K. Ptaszynska, J. Sitkowski, and E. Bloszyk 3-Ethoxy Lactarane Sesquiterpenes of Lactarius Origin Antifeedant Activity. Polish J. Chem., 66, 1249 (1992). 

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. 

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. 

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... 

Compound 2.1 is one of the very few examples of sesquiterpenes from Lactarius, where one of the geminal methyl groups occurring in all skeletons has been oxidized to a hydroxy methylene function. 

Structure elucidation of 5-lactaranolides other relevant chemical transformations involved the conversion of the lactone into the furan ring and addition reactions to double bonds (hydrogenation, hydroboration, epo-xidation, osmylation). A brief account of these reactions will be included in the chapter on chemical conversions of Lactarius sesquiterpenes. 

Lactaranolide derivatives included in Part 12 are produced by silica gel degradation of velutinal esters (7.28, 7.30), methylvelutinal (7.17) or free velutinal itself (for a discussion of these transformations see the chapter on chemical interconversions of Lactarius sesquiterpenes). The compounds upon acidification underwent aromatization to form furanoid derivatives (see Part 18). Under these conditions dehydration reactions took place and also dienes were formed (72). 

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). 

In this chapter, we review the literature on total syntheses of Lactarius sesquiterpenes. For space limitations we have limited our comments to the most intriguing synthetic steps. Moreover, we have not included incomplete synthetic approaches although they often rely on... 

Battaglia, R., M. De Bernardi, G. Fronza, G. Mellerio, G. Vidari, and P. Vita-Finzi Fungal Metabolites. VIII. Structures of New Sesquiterpenes from Lactarius scrobiculatus. J. Nat. Prod., 43, 319 (1980). 

Hansson, T., Z. Pang, and O. Sterner The Conversion of [12- H3]-Labelled Velutinal in Injured Fruit Bodies of Lactarius vellereus. Further Insight into the Biosynthesis of the Russulaceae Sesquiterpenes. Acta Chem. Scand., 47, 403 (1993). 

De Bernardi, M., G. Mellerio, G. Vidari, P. Vita-Finzi, and G. Fronza Fungal Metabolites. Part 15. Structure and Chemical Correlations of Uvidin C, D, and E, New Drimane Sesquiterpenes from Lactarius uvidus Fries. J. Chem. Soc. Perkin Trans. I, 2739 (1983). 

Sterner, O., O. Bergendorff, and F. Bocchio The Isolation of a Guaiane Sesquiterpene from Fruit Bodies of Lactarius sanguifluus. Phytochemistry, 28, 2501 (1989). 

Sterner, O. The Co-formation of Sesquiterpene Aldehydes and Lactones in Injured Fruit Bodies of Lactarius necator and L. circellatus. The Isolation of e/ i-Piperalol. Acta Chem. Scand., 43, 694 (1989). 

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