Karahana ether

Gosselin and colleagues169 prepared Karahana ether (264), starting with an asymmetric Diels-Alder reaction between chiral diene 261 and maleic anhydride. This reaction yielded diastereomers 262 and 263 in a 1 4 ratio (equation 72). 

Armstrong RJ, Weiler L (1986) Synthesis of ( )-karahana ether and a ( )-labdadienoic acid by the electrophilic cyclization of epoxy allylsilanes. Can J Chem 64 584—596... 

Where functional groups are present which are more readily oxidized than the ether group, multiple reactions can occur. For example, in their total synthesis of (-i-)-tutin and (-i-)-asteromurin A, Yamada et al. observed concomitant oxidation of a secondary alcohol function in the oxidation of the ether (30) with ruthenium tetroxide (equation 24). The same group successfully achieved the simultaneous oxidation of both ether functions of the intermediate (31) in their related stereocontrolled syntheses of (-)-picrotox-inin and (-i-)-coriomyrtin (equation 25). Treatment of karahana ether (32) with excess ruthenium tetroxide resulted in the formation of the ketonic lactone (33) via oxidation of both the methylene group adjacent to the ether function and the exocyclic alkenic group (equation 26). In contrast, ruthenium tetroxide oxidation of the steroidal tetral drofuran (34) gave as a major product the lactone (35) in which the alkenic bond had been epoxidized. A small amount of the 5,6-deoxylactone (17%) was also isolated (equation 27). This transformation formed the basis of a facile introduction of the ecdysone side chain into C-20 keto steroids. 

Karahana ether (196), isolated from Japanese hops, is also a 1,1,2,3-tetra-methylcyclohexane derivative, and has been synthesised by Coates and Melvin by a route that they suggest may resemble the biogenetic pathway.Their synthesis consists in cyclising geranyl acetate (194) with benzoyl peroxide in the presence of cupric saltsand hydrolysing the resulting mixture to the corresponding diols, from which the cis-diol (195) is separated and converted to the ether with p-toluenesulphonyl chloride in pyridine at room temperature. 

This process was applied to the synthesis of the Karahana ether. 

A number of oxacyclic natural products were synthesized via carbocycle-forming radical reaction of oxacyclic intermediates. An early example is the synthesis of (-)-dihydroagarofuran (170) by Biichi [109] (Scheme 58). The bridgehead chloride 168 obtained from the corresponding hydroxy ketone was amenable to radical cycliza-tion, and the tricyclic ether 169 was duly obtained. The aplysin synthesis [110] provides another example, and (—)-karahana ether (173) was synthesized via radical cyclization of the substrate 171 [111] (Scheme 59). Lactonic natural products (-1-)-eremantholide A [112], alliacolide [113], and (-)-anastrephin [114] were prepared via a variety of carbocycle-forming radical cyclization reactions. In the total synthesis of spongian-16-one (176) [115] (Scheme 60), the butenolide moiety in the substrate 174 served as the final radical acceptor for three consecutive 6-endo-. rig cyclizations. 

The volatile monoterpene karahana ether 48 shows an xo-methylene function which can be retrosynthetically correlated with a triple bond, that is, it can be generated via a radical-mediated 6-exo-dig intramolecular cyclization of a suitable alkyl radical onto an alkyne function (equation 42) . ... 

Figure 1. Structures of hop oil components. Key I, humulene II, humulene epoxide I III, humulene epoxide II IV, humulol V, humulenol II VI, humula-dienone VII, a-eudesmol VIII, -eudesmol IX, hop ether X, karahana ether XI, p-ionone and XII, j3-damascenone.

These compounds may well have an effect on the hop aroma of beer but if they are responsible for the traditional "kettle hop" aroma, then the concentration of humulene in hops should not be so important. Further, from Table 111 the concentration of hop ether and karahana ether in hop oils does not correlate well with aroma quality. Tressl (17) has noted that the concentrations of these two ethers go up dramatically as hops age. 

Hop ether (136) and karahana ether (139) are monoterpenoid compounds which occur in Japanese hop (Shinshu-wase) 426), while the occurrence of (-h)-matatabi ether (138) and of its isomer (137) is limited to the essential oil of Actinidia polygama Franch. et Sav. (Ternstroemiaceae) 261, 716). 

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