Humulenic acids

Homoterpenyl methyl ketone, Tl Homothujadicarboxylic acid, T7 Hopane, T45 Hopeaphenol, Y15 Hopenone I, T45 Humulene dioxide, T30 Humulene epoxides, T30 Humulenic acids, Y9 ... 

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... 

N.A. Humulone, lupulone, humulene, alpha, beta-acids, polyphenols, steroids, resins, tannins.103>142 143 Sedative effect, hypnotic, stomachic, diuretic. Against gram-positive organisms and tuberculosis. 

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... 

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... 

An investigation of the acid-catalysed cyclization of humulene (151) has provided results69 identical with those outlined in last year s Report.8 The isolation70 of... 

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. 

Homoaporphins, 201 Homobenzoqulnones, 339 Homogeranic acid, 295 Homopropargylic alcohols, 279-280 Humulene-4,5-epoxide, 64 Hunsdiecker reaction, 293 Hydrastine, 214, 215 Hydrazides, 429 Hydrazine, 236-237, 351... 

X-Ray analyses of two heavy-atom derivatives of illudol (203) and marasmic acid (204) have confirmed the ds-fused hydrindane skeletons in each and this fact is in accord with the stereochemistry of the hypothetical precursor (205) derivable from humulene. Matsumoto and co-workers have now completed... 

C(2) of mevalonic acid (56a) as well as the known absolute configuration of illudol, the stereochemical outcomes of the early steps can be inferred (equation 7) farnesyl pyrophosphate (73) cyclization has occurred exclusively on the si face of the distal double bond the humulene (74) cyclization must have occurred from the RSR-CT conformation and protonation at C(10) has taken place at the re face of the 9,10-double bond ... 

Unsymmetrical compounds can also be prepared via mixed Kolbe electrolyses of different carboxylates (heterocoupling). The disadvantagous but unavoidable formation of symmetrical dimers can be suppressed to the formation of essentially one by-product if the cheapter carboxylic acid is used in a 5- to 10-fold excess. Hydrogenated carotenoids, saturated and unsaturated fatty acids, optically active )-hydroxycarboxylic acids, and intermediates for the preparation of muscone and humulene have been obtained in this way [177b]. 

Later work by Parker et a/.demonstrated that extended treatment of humulene with aqueous sulfuric acid in acetone led largely to the bicyclo[5.3.0]deca-2,10-diene (115), via initial formation of humulol... 

The three monoepoxides of humulene, i.e. (136), (150) and (162), occur in nature, and there is every reason to assume that each epoxide is involved separately in transannulation processes leading to various fused-ring systems found amongst the sesquiterpenes. All three humulene monoepoxides have been synthesized and their individual chemistry with Lewis acids has been examined in an effort to effect their biogenetic conversions to natural teipenes. 

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). 

Humulene 4,5-epoxides 10 were converted to cyclopropanes 11 upon treatment with boron trifluoride-diethyl ether complex in a mixture of acetic anhydride and acetic acid. ... 

Thus, reaction of humulene (1) with A -bromosuccinimide in aqueous acetone, or with hypobromous acid, gave a 1 1 mixture of 9-bromo-l,4,4-trimethyl-8-methylenecycloundeca-l,5-diene (2) and 5-bromo-8-hydroxy-4,8,ll,ll-tetramethyltricyclo[7.2.0.0 ]undecane (3), each isolated in 25% yield. In this tricyclic compound six neighboring asymmetric centers were formed in one step with a very high degree of stereoselectivity. ... 

Treatment of the epoxide 4, prepared by treatment of humulene with pervanadic acid (H2O2-V2O5), with 1.8 M sulfuric acid and acetone (1 1) at O C for 30 minutes gave the diol 5 as the sole product in 95% yield. ... 

Direct methods of converting humulene (332) into its 8,9-monoepoxide (337)t and into zerumbone (338) have proved to be very inefficient. Shirahama et al. have now brought about these conversions by indirect means. Thus, for the epoxide (337),169 humulene is first transformed to the acetate (339) by treatment with boron trifluoride etherate in glacial acetic acid followed by mono-epoxidation. Reduction of this acetate with LiAlH, followed by elimination with mesyl chloride in pyridine gives the epoxide (337). In the case of zerumbone (338),170 the readily... 

Asymmetric synthesis. Following the procedure of Cope et al. (2, 272), Chamberlain and McKervey1 prepared the optically active complex (3) of humulene (1) by treatment with (—)-/ranj-dichloro(ethylene)-a-methylbenzylamine platinum-(11), (2). Epoxidation of (3) with perlauric acid gives optically inactive humulene (1) and humulene 1,2-epoxide with ctD= —3.2°. Since the natural epoxide has an... 

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... 

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