Humulene rearrangement

The three mono-epoxides of humulene 1 are naturally occurring, and it is believed that they are in vivo precursors of other bicyclic and tricyclic sesquiterpenes. In vitro experiments have demonstrated that the 1,2- and 4,5-epoxides undergo facile acid-catalysed rearrangement, and it has been shown recently that treatment of a chloroform solution of the 8,9-epoxide with tin(IV) chloride at -60°C for 15 minutes gives a variety of hydrocarbons and one major product (25%), the alcohol 2. 

Lewis Acid Catalysed Rearrangement of Humulene 8,9-Epoxide... 

Complete details of the acid-catalysed rearrangement of humulene 1,2-epox-ide (249) have now been presented. With 1.8M-sulphuric acid in acetone at 0 °C for 30 min the sole product is the previously "known tricyclic diol (250). After an extended period this diol gives rise to five other identified products. 

Formolysis of (264) produces the formate ester of (259) and (265) in 66% and 20% yield respectively the latter hydrocarbon is related to the pentalane class of sesquiterpenoids (see below). A study of this rearrangement, again using a deuteriated substrate, provided evidence for the pathway outlined in Scheme 38. Matsumoto et have also studied the mechanism of formation of the two tricyclic ethers (257) and (260) [with Hg(OAc)2] and the three tricyclic ethers [with Hg(N03)2] derived from humulene after NaBD4 work-up. Under these conditions the five deuteriated products are (266)—(270) respectively. The... 

In contrast to the fascinating transannulation reactions associated with humulene-1,2- and humulene-4,5-epoxides, humulene-8,9-epoxide (161) undergoes transannulation and rearrangement in the presence of SnCU leading only to the bicyclic alcohol (162), related to the rearrangement product (115) of hu-mulene itself (Scheme 20). ... 

A number of biomimetic syntheses have included Wagner-Meerwein rearrangements. A chemical conversion of humulene (48) to sterpurene (50) involved an interesting series of Wagner-Meerwein rearrangements (see Scheme 19).- - Humulene (48) was converted to the cyclooctenol (51) and thence to the bromide (52) via the protoilludyl cation (49). Treatment of (52) with silver acetate in acetic acid gave racemic sterpurene (50). In contrast the epimeric bromide (53) gave (54). 

When the C1-C2 double bond is deactivated, for instance by oxidation of the methyl group to an aldehyde group as in 11, opening of the oxirane ring by trimethylsilyl triflate provided a homoallyl carbenium ion which then underwent transannular Ti-cyclization but with participation of the C8-C9 double bond leading to a mixture of secoprotoilludane derivatives 12 and 13. In this case the rearrangement took place from a different C-C conformation, where in an intermediate step an additional Z/ isomerization of the C1-C2 double bond occurred. Reaction of the 8,9-epoxide of humulene with tin(IV) chloride led initially to formation of a cationic center at C9, but internal 7r-cyclization yielded an alcohol with a hydroazulene structure. ... 

Naya and Kotake, in an examination of Japanese hop oil, have isolated three humulane-type compounds, viz., humuladienone (161, R = Me), humulenone II (161,R = =CH2), and humulol (162), in addition to the tricyclic diol (163, R = OH), m.p. 207 °C. This diol has already been prepared in two different ways (a) Sutherland et treated humulene (164) with AT-bromosuccini-mide in aqueous acetone and converted the resultant bromohydrin (163, R = Br) to the diol (163, R = OH), m.p. 205—206 °C, by hydrolysis, (b) McKervey and Wright obtained the same diol, m.p. 201—203 °C, by acid-catalysed (20% sulphuric acid) rearrangement of humulene 1,2-epoxide (165), a known natural product. On the basis of these findings and the fact that both caryophyllene (166) and humulene can be derived from the above bromohydrin by two in vitro steps, McKervey and Wright postulated that humulene 1,2-epoxide may be involved in the biosynthesis of the tricyclic diol and caryophyllene. This postulate does not, however, readily accommodate the observed rotations of the relevant... 

Other examples of cyclization reactions involving alkenyl groups are the formation of the pentacyclic ether (133) from the BF3 OEt2-catalysed rearrangement of (132) and the transannular cyclization of humulene 9,10-oxide (134) to (135) (70%) in BF3 OEt2-acetic anhydride. ... 

In dioxan-water containing 0.02 mol 1 perchloric acid, humulene is hydrated to humulol (256) which then rearranges to give a-caryophyllene alcohol (257 20—25 %) and a mixture of bicyclo[5,3,0]decenes (75 %) of which (258 90% of the mixture) is the major component. Mechanisms for these rearrangements were proposed based on... 

In studies of the rearrangements of epoxides of humulene, Bryson et have shown that the 8,9-epoxide (155) undergoes Lewis acid-catalysed rearrangement producing one major alcohol (156), which is related to the bicyclodiene (157) obtained from acid-catalysed rearrangement of humulene itself. 

Futatsugi K, Yamamoto H (2005) Studies on the mechanism of sesquiterpene biosynthesis, humulene-germacrene rearrangement Angew Chem Int Ed 44 1924-1942... 

CHAlUHGtl Humulene and a-caryophyllene alcohol are terpene constituents of carnation extracts. The former is converted into the latter hy acid-catalyzed hydration in one step. Write a mechanism. (Hint The mechanism includes cation-induced double-bond isomerization, cyclizations, and rearrangements that may involve hydrogen and alkyl-group migrations. Two of the intermediates in the mechanistic sequence are shown five carbon atoms are identified by starts to help you track their positions through the process.)... 

The biosynthesis of illudin S (I) from a farnesyl precursor requires a carbon skeletal rearrangement at some stage. The scheme shown on page I39 is essentially that of Nakanishi et al. (1965)- The cychzation of farnesyl pyrophosphate (III) to humulene (IV), a hydrocarbon widely distributed in plants, has been proposed as the first step in the biosynthesis of several other terpenoids from III. Nakanishi etal. (1965) proposed that OH attacks humulene (IV), but since it appears that H attacks humulene (IV) to produce marasmic acid, Dugan, et al. (1965) have implied that it is H which attacks in the illudin case. The hydrocarbon V is oxidized to the cyclobutyl cation VI, which rearranges as shown to the hydrocarbon VII. Oxidations of VII at the starred sites produce illudin M (II), which is further oxidized in some cases to illudin S (I). 

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