Humulanes, Caryophyllanes, and Himachalanes

If the initial cyclization of trans trans- or cis, /raw -farnesyl pyrophosphates (52-OPP and 51-OPP) occurs upon the terminal (10, 11) double in an anti-Markovnikov orientation, eleven-membered cyclic dienyl carbonium ions are produced. Deprotonation of the trans, trans-intermediate affords humulene (97) while bis-homoallyl- cyclobutyl carbinyl cyclization furnishes, after elimination, caryophyllene (99). Although the all traw -configuration of the three double bonds in humulene would appear to require trans, rra -farnesyl pyrophosphate as precursor, the possibility exists that the immediate predecessor of caryophyllene is cis, /rtz 5-farnesyl (or cisoid nerolidyl) pyrophosphate. 

Humulene reacts with electrophiles initially at the trisubstituted 6,7 double bond in a Markovnikov fashion. With N-bromosuccinimide in aqueous acetone, the attack of bromonium ion triggers a double cyclization to tricyclic bromohydrin (104) 147). The formation of the /mn -fused cyclobutane ring by electrophilic cyclization onto the 2,3-double bond is similar to the second ring closure in the caryophyllene biogenesis. By dehydration and reductive cleavage of the three-membered ring, it was possible to convert (104) into caryophyllene. 

In a very similar manner 6,7-epoxyhumulene (105) is converted to tricyclohumuladiol (106) and humulenol (107), both of which have been isolated from natural sources 148, 149). However, since the starting epoxide (105) itself is a known natural product, the close parallelism here raises the possibility that (106) and (107) may be artefacts of the processing and/or isolation conditions. 

Bisarya and Dev have examined the hydrolysis of allohimachalyl tosylate (lOl-OTs) a reaction of obvious biogenetic significance 157). The stereochemistry of the nucleophilic capture of the intermediate carbonium ion in this solvolysis is apparently exactly the same as in the biosynthesis since the only alcohol products are himachalol (lOl-OH) and allohimachalol (103). The naturally occurring sesquiterpenes a- and P-himachalene (108 and 109) are also formed. 

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