Bisabolan

Several examples of the monocyclic isothiocyano sesquiterpenoids having the bisabolane (83) skeleton are known. Along with the hydrocarbon theonellin (84), isothiocyanate 86 and formamide 87 were obtained from the Okinawan sponge Theonella cf. swinhoei. It seems remarkable, but not unusual, that not only was the amide the major constituent, but the isonitrile 85 was the missing member of the triad [57], Relative stereostructures were indicated by NMR analysis of theonellin formamide (87) and its transformation products. 

The epimeric compounds, e.g., 88 and 89 from a Hawaiian Ciocalypta sponge [55] and 90 from a Pohnpei Halichondria sp., may share a common sp2-carbon center in the biosynthesis of the bisabolane skeleton of these compounds. 

The bisabolanes, of which eight have been reported in these studies, also deserve special mention. Again, Z,E-farnesyl pyrophosphate is the putative progenitor. One study (13) reported 3-bisabolol (199) to be about 34% of the volatile alcohol fraction, making it about 5% of the total essential oil. a-Bisabolene (193) is representative of the hydrocarbons of this group. 

These compounds range through monocyclic (with a bisabolane framework), bicyclic (with an eudesmane, amorphane, axane, guaiane, isodaucane, or gorgonane framework), tricyclic (with an aromadendrane, cubenane, maaliane, pupukeanane, or trachyopsane framework), and spiro[4,5]decane carbon skeletons. 

Higher yields of acetonides have been obtained by transacetalization of a 1,4-diol unit with dimethoxypropane, as demonstrated with the protection of 193, an intermediate in the synthesis of a cytotoxic bisabolane sesquiterpene (+)-curcuphenol (Scheme 54) <1998TA2215>. 

Isoprenylation of Isopropenyl groups.1 Cyclic terpenes substituted by an isopropenyl group can be converted into sesquiterpenes with the bisabolane skeleton by addition of HOC1 under biphasic conditions to give an allylic chloride (10, 208-209) followed by a zinc-induced reaction with isovaleraldehyde to form an isomeric mixture of homoallylic alcohols. 

The related bisabolane 295 was isolated from the roots of Ligularia cymbulifera... 

Zhu Y, Yang L, Jia Z-J (1999) Novel Highly Oxygenated Bisabolane Sesquiterpenes from Cremanthodium discoideum. J Nat Prod 62 1479... 

Davyt D, Fernandez R, Suescun L, Mombru AW, Saldana J, Dominguez L, Fujii MT, Manta E (2006) Bisabolanes from the Red Alga Laurenca scoparia. J Nat Prod 69 1113... 

Hernandulcin is a bisabolane sesquiterpene isolated from the herb Lippia dulcis Trev. (Verbenaceae), which is native to Mexico, and has been reported to be 1500 times sweeter than sucrose.44 45 The natural product has a 6S, 1 xS" configuration, and of the four possible stereoisomers, only this one has intense sweetness.46 47 Another sweet substance, 4,3-hydn> x v hern a n d u I cm, was isolated from a sample native to Panama.46 The sweetness and bitterness of hernandulcin have been reported to linger in the mouth for sometime. This compound is rather thermolabile. 

A large number of oxygenated bisabolane sesquiterpenoids (53)—(71) have been isolated and identified by Bohlmann s group " (see also ref. 342). A third... 

The catalyzed ene reaction has been used for isoprenylation of monoterpenes with an isopropenyl side chain to form sesquiterpenes of the bisabolane group. An example is the three-step conversion of (+)-limonene (1) into / -bisabolene (2). ... 

This selective metalation has been used for the synthesis of several bisabolane sesquiterpenes. Thus the sesquiterpene (- )-J -bisabolene (7) can be synthesized in one step from metalated ( —)-limonene by reaction with I-bromo-3-methyl-2-butene. Two... 

Antibacterial bisabolane sesquiterpenes and tricyclic sesquiterpenes, the latter consisting of an irregularly built C15 backbone, were also isolated from Leontopodium alpinum [36]. These compounds showed significant antibacterial activity towards Enterococcus faecium. 

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