Frullania Frullanolide

New additions to the eudesmanolide family include (610)—(635).105 154 220 222-231,247,249,276-282 examination of liverwort species continues to reveal interesting new structures such as those of (+)-p-frullanolide (636) and (+)-brothenolide (637) from Frullania brotheri283 and (+)-crispatanolide (638) from Makinoa crispata.2Si The last compound is unique in the eudesmane field having a 8-lactone attached between C-7 and C-14. 

Many instances of positive patch-test reactions to Frullania or frullanolide have been reported in patients sensitised to sesquiterpene lactones from plants in the family Compositae. Equally, forest workers who have become sensitised to liverworts may well exhibit crossreactions to plants in the families Compositae (Mitchell et al. 1970, 1971 Storrs et al. 1976 Fernandez de Corres and Corrales Torres 1978 Hausen and Osmund-sen 1983 Fernandez de Corres 1984 Gon alo 1987 Gon alo and Gon alo 1991 Lovell and Rowan 1991), Magnoliaceae (Fernandez de Corres and Corrales... 

Adams RM (1990) Forestry workers. In Adams RM (ed) Occupational skin disease. Saunders, Philadelphia, pp 625-626 Asakawa Y (1982) Chemical constituents of the Hepaticae. Prog Chem Org Nat Products 42 1-285 Asakawa Y, Benezra C, Ducombs G, Foussereau J, Muller JC, Ourisson G (1974) Cross-sensitization between Frullania and Laurus nobilis the allergen of laurel. Arch Dermatol 110 957 Asakawa Y, Matsuda R, Toyota M, Takemoto T, Connolly JD, Phillips WR (1983) Sesquiterpenoids from ChiloscyphuSy Clasmatocolea and Frullania species. Phytochem 22 961-964 Barbier P, Benezra C (1982) Stereospecificity of allergic contact dermatitis (ACD) induced by two natural enantiomers, (+)-and (-)-frullanolides, in guinea pigs. Naturwissenschaften 69 296-297... 

Frullanolide, a sesquiterpene lactone, is contained in Frullania tamarisci (l) Dum. (L-Frullanolide) and Frullania dilatata (l) Dum. (o-frullanolide). Sensitivity causes mainly airborne contact dermatitis in forest rangers, lumbermen, sawyers, carpenters, and merchants in rough timber. 

Incubation of (-)-frullanolide (226), obtained from the European liverwort Frullania tamarisci subsp. tamarisci that causes a potent allergenic contact dermatitis, was incubated by A. niger to give dihydrofrullanolide (227), nonallergenic compound in 31.8% yield. In this case, C11-C13 dihydro derivative was not obtained (Hashimoto et al., 2005). 

Frullanolide (338), with a d s-lactone ring, has been isolated from the epiphytic liverwort, Frullania tamarisci. The structure was deduced from its spectral properties (775,255, 287) and confirmed by conversion to l,2-dihydro-6-epi-P-santonin (366) also obtained from 6-epi-P-santonin (367) (775, 287) (Scheme 40). The enantiomer (339) of (338) was isolated from European F, dilatata (30, 175, 287). 

In North America and Europe, it has long been known that some occupational allergies are associated with handling of wood on which epiphitic liverworts grow. The hapten of this allergy is a sesquiterpene lactone, (—)-frullanolide (338), isolated from Frullania tamarisci ssp. tamarisci, or ( + )-frullanolide (339) from F. dilatata 14,18, 30, 32,37,175, 255, 287). The isolation of these compounds represented the first discovery in bryophytes of compounds with biological activity in humans. The eudesmanolides (349) and (352) and the eremophilanolide (322) also caused intense allergies. Patients sensitive to Frullania species are all sensitive to at least one of the lactones isolated from F. dilatata 30). 

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