Humulene oxide

Two transannular cyclizations have been reported which lead to isomers of 677. Thus, treatment of 677 or 678 with boron trifluoride etherate gives rise to capnellene (679) Also, conversion of humulene 6,7-oxide (680) to tricyclic epoxide 681 has provided the opportunity for trimethylsilyl triftate-promoted... 

Hordenine Lf , P1 2S172 Humulene oxide I 1 7S172 Humulene oxide II 1 7S172 Humulene oxide 0 ... 

The main purpose of using hops in beer is to add bitterness to the final product. A series of compounds referred to as Ci and B-acids are responsible for this taste (1 ). A secondary, ill defined flavor (flavor referring to smell and taste) is also imparted to beer by brewing with "aroma hops." Not all hop varieties are considered "aroma hops," and there is evidence that the flavors Imparted to beer by different aroma hops are different ( ). There has been considerable controversy in recent years as to the nature and source of this flavor. Researchers have credited ter-pene alcohols (2, ), humulene oxidation products (, ), multi-cyclic terpenoid ethers (6) and carotenoids (.6) as being in part responsible for this flavor. 

At present there is little agreement as to what compounds are responsible for "kettle hop" aroma. The theory of Peacock and Deinzer ( ) that it is humulene oxidation products seems most in agreement with the traditional prejudices of brewers. Long hop storage, long wort boiling times and a high concentration of... 

Sampling time 60 min extraction temperature 80°C. Monoterpenes a-pinene, p-myrcene, a-phellandreneand limonene sesquiterpenes a-cubebene, a-copaene, p-elemene, p-caryophyllene, a-humulene, y-muurolene, p-eudesmene and caryophyllene oxide diterpenes cembrene A and isoincensole acetate. 

The first observation is the similarity between the chemical compositions of both the Boswellia carteri and Boswellia sacra. For these three olibanum samples, a-pinene (2), (3-myrcene (8) and limonene (14) are the predominant monoterpenes. p-Caryophyllene (73) is the major sesquiterpene besides a-copaene (65), a-humulene (also called a-caryophyllene) (78) and caryophyllene oxide (95). The characteristic olibanum compounds isoincensole and isoincensole acetate (128) together with cembrene A (120) are the main diterpenes. 

Boswellia serrata olibanum has a chemical composition close to that of both the B. carteri and of B. sacra, but contains compounds that are absent in those from other Boswellia and could be used as markers methylchavicol (38), p-anisaldehyde (47), methyleugenol (70), isocaryophyllene (82), sesquiterpene 91, elemicin (92) and an unidentified diterpene (124) eluting between cembrene C (123) and verticilla-4(20),7,ll-triene (125). It is devoid of (5-caryophyllene (73), a-humulene (78), caryophyllene oxide (95) and bornyl acetate (50). 

Eight olibanum samples of unknown botanical origin have been analysed [26]. The chemical compositions are summarized in Table 10.3 for three of them. Both the olibanum coming from Somalia and that from a market in Ta izz (Yemen) have been attributed to Boswellia carteri or sacra on the basis of the occurrence of the characteristic diterpenes isoincensole and isoincensole acetate (128) together with diterpene 126. The absence of methylchavicol (38), oxygenated sesquiterpene 91 and diterpene 124 and the presence in relatively large amount of (3-caryophyllene (73), ot-humulene (78) and caryophyllene oxide (95) excluded the hypothesis of a B. serrata sample. 

Resistant hirsutum race stocks Texas No. 254 and 810 also are deficient of bisabolene and B-bisabolol stocks 810, 1055, and 1123 have greatly increased caryophyllene oxide contents and stock 953 has greatly reduced concentrations of caryophyl 1 ene, caryophyl 1 ene oxide, and humulene (Table II). It is tempting to attribute the known increased resistance to insects in the Texas race stocks to the changes in volatile profiles, but this hypothesis remains to be proven. 

The fermentation broth of various Streptomyces species can be separated into an acidic fraction shown to contain pentalenic acid 776) The somewhat less oxidized pentalenolactone precursor has been independently prepared from humulene from which is is probably derived biogenetically Thus, treatment of humulene with mercuric nitrate followed by aqueous potassium bromide solution gave two bromo-mercury derivatives which were oxygenated in the presence of sodium borohydride. The resulting pair of diols (770 and 771) were separately converted to exo methylene... 

Abraham et al. [144-146] studied the biotransformation of caryophyllene (190) and humulene (196) by Diplodia gossypina (ATCC 10936) and two strains of Chaetomium cochliodes (DSM 63353 and ATCC 10195), Fig. (38) and Fig. (39). Sixty three products, including 49 that had never been described previously, were obtained and tested for their biological activity [147]. More recently, the bioconversion of (-)-caryophyllene by Chaetomium cochliodes IFO 30576 was also studied by another group [148]. The substrate was first epoxidized at the C-C double bond, producing (-)-caryophyllene-4,5-oxide (191), which was then hydroxylated at the ge/n-dimethyl group and C-7 position giving 193. 

Amongst the monocyclic sesquiterpenes, the plant growth hormone (+)-abscisic acid 446 and a-humulene 451 are found which both can be synthesized by Wittig reactions. To synthesize (+)-abscisinic acid 446 D. L. Roberts et al. 239) converted a-ionone 444 into the allylic alcohol 445 by /-butyl chromate oxidation. 445 is reacted with ethoxycarbonylmethylene-triphenylphosphorane 238 and subsequently... 

The main essential oil components of the edible fruits of G. huillensis Welw. ex. Oliv. growing wild in the Gutu and Rusape areas of Zimbabwe are a-humulene (23.0%), valencene (18.2%), caryophyllene (12.6%), caryophyllene oxide (6.3%) and 8-selinene (5.0%) (Chagonda Lameck and Chalchat, 2005). 

Asymmetric Epoxidation. McKervey and co-workers have effected the asymmetric epoxidation of humulene. Complexation of humulene with (2) in a 1 2 ratio followed by peracid oxidation gave (—)-humulene 1,2-epoxide in 37% ee (eq 1). ... 

Croton sylvaticus Hochst. The essential oil of semi-dried C. sylvaticus leaves (0.14%) contained mainly the sesquiterpenes p-caryophyllene oxide (35%) and a-humulen-1,2-epoxide (12%) (56). The aqueous extract of the stem bark of C. sylvaticus reduced exploratory activity, prolonged ether anesthesia, relaxed the muscles and had analgesic effects on mice (5 7). The plant is used for treatment of swellings caused by kwashiorkor, for tuberculosis and as a purgative (35). 

Euphorbiaceae Croton sylvaticus Hoscht. Leaves SD 0.14 P-caryophyllene oxide, a-humulen-1,2-epoxide 56... 

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. ... 

Qccurance and Identification. An early report of cotton volatile composition by Minyard et al. (44) involved steam distillation of large quantities of leaves and flowers. Major compounds identified included the monoterpenes a-pinene, B-pinene, myrcene, trans-B-ocimene, and limonene ( 4). Several other monoterpene hydrocarbons were also present in low concentration. Since that report, many other terpenes have been identified in cotton essential oil steam distillates and solvent extracts. These compounds include cyclic hydrocarbons such as bisabolene, caryophyllene, copaene and humulene (45-47), the cyclic epoxide caryophyllene oxide (45), cyclic alcohols such as bisabolol, spathulenol, and the aromatic compound... 

The microbial transformation of humulene, a substrate showing a structure similar to that of germacrone, was studied by Abraham and Stumpf using a screen of about 300 strains1175 . This led the authors to select the fungi Diplodia gossypina and Chaetonium cochlioides for preparative scale experiments. It was thus observed that the main reaction path starts with the epoxidation of the 1,2-double bond, as shown by direct biotransformation of this monoepoxide obtained by chemical synthesis. This is then further oxidized to yield a multitude of products including diepoxides and hydroxy-epoxides (Fig. 16.1-28). 

The first transannulation of humulene-4.5-epoxide with the 1,2-double bond is disfavored when the C-2 methyl group is oxidized to a carbonyl substituent since the 1,2-double bond is now electron deficient. In this case reaction of epoxide 10 in the presence of trimethylsilyl trifluo-romethanesulfonate leads to the bicyclo[6.3.0] systems 11 and 12 in good yield after reaction with the 8,9-double bond followed by a nonregioselective proton elimination75. 

Humulene biosynthesis probably involves the intermediacy of a monocyclic carbonium ion or its biological equivalent [c/. (303)] derived from trans,trans-farnesyl pyrophosphate (16), A recent investigation based on this idea has shown that treatment of the ( , )-mesylate (303 Z=OMs) with dime thy laluminium phenoxide provides humulene (304) in excellent yield. The corresponding (Z, )-isomer, when treated with di-isobutylaluminium 2,6-dibutyl-4-methyl-phenoxide, is efficiently converted into germacrene (307) whereas the E,E)-isomer under these conditions provides a mixture (2 1) of humulene (304) and germacrene A (305). Monohydroboration-oxidation of caryophyllene... 

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. ... 

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