Sesquiterpenoid Ethers

Whereas sesquiterpenoid hydrocarbons, with few exceptions, have inferior characteristic organoleptic properties, the ethers of this series — as far as they are known — are distinguished by outstanding odor qualities. Once the general value of these compounds as aroma components is recognized, as it is the case with the monoterpenoid ethers, the importance of this group of compounds will rapidly grow. 

Four ethers of the bisabolane series have so far been found in nature. The sole member of this series whose odoriferous properties 

Caparrapi balsam is a fragant oil from Colombia which is stated to be of some therapeutic value 18), A bicyclic ether (210) 18,59,93) called caparrapi oxide was isolated as the main component (up to 43%) from this oil. Whereas the natural product (210) is virtually odorless, its diastereoisomer (211) has pronounced amber-like odor properties 455). 

Apart from a few compounds isolated from aquatic plants 543, 604, 652), sesquiterpene derivatives with a reduced carotenoid structure [mono-cyclofarnesane (555)] have not been detected in terrestrial plants. Thus, 9-vinyl-7,8-dihydro-a-ionol is still a synthetic product which, however, shows a biogenetic relationship to the ethers of the caparrapi series (210)/(211) 348). 

Guaioxide (212) which was first separated from guaiac wood oil Bulnesia sarmienti Lor.) 29, 140) has a distinct woody, musty odor character 443). The aerial parts and the roots of the Chinese herb 

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Asakawa, Y, T. Hashlmoto, Y. Mizuno, M. Tori, and Y. Fukuzawa, 1992. Cryptoporic acids A-G, drimane-type sesquiterpenoid ethers of isocitric acid from the fungus Cryptoporus volvatus. 31 ... 

Methylene difluorocyclopropanes are relatively rare and their rearrangement chemistry has been reviewed recently [14]. In addition, electron deficient alkenes such as sesquiterpenoid methylene lactones may be competent substrates. Two crystal structures of compounds prepared in this way were reported recently [15,16]. Other relatively recent methods use dibromodifluoromethane, a relatively inexpensive and liquid precursor. Dolbier and co-workers described a simple zinc-mediated protocol [17], while Balcerzak and Jonczyk described a useful reproducible phase transfer catalysed procedure (Eq. 6) using bromo-form and dibromodifluoromethane [18]. The only problem here appears to be in separating cyclopropane products from alkene starting material (the authors recommend titration with bromine which is not particularly amenable for small scale use). Schlosser and co-workers have also described a mild ylide-based approach using dibromodifluoromethane [19] which reacts particularly well with highly nucleophilic alkenes such as enol ethers [20], and remarkably, with alkynes [21] to afford labile difluorocyclopropenes (Eq. 7). 

Several species of Fusarium infect com, wheat, barley, and rice. Under favorable conditions they elaborate a number of different types of tetracyclic sesquiterpenoid mycotoxins that are composed of the epoxytrichothecene skeleton and an olefinic bond with different side chain substitutions (fig. 9). Based on the presence of a macrocyclic ester or ester-ether bridge between C-4 and C-15, trichothecenes are generally classified as macrocyclic (type C) or nonmacrocyclic (types A and B) (table 5). Other fungal genera producing trichothecenes are Myrothecium, Trichoderma, Trichothecium, Acremonium, Verticimonosporium and Stachybotrys. The term trichothecenes is derived from trichothecin, the first compound isolated in this group [115, 147-153]. 

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... 

Further work on the sesquiterpenoids of the mushroom species Lactarius has resulted in the isolation of 15-hydroxyblennin A (289) and the four related compounds (290)—(293). " The two ethyl ethers (291) and (293) are almost certainly artefacts of the isolation procedure. Further details of the chemistry of isolactarorufin (294) have been published. The absolute stereochemistry of this unusual tetracyclic compound has not been ascertained as yet. The confusion concerning the precise structures of velleral (295), vellerolactone (296), and pyrovellerolactone (297) has now been firmly resolved by the synthesis of all three compounds as racemates (Scheme 43). 

The structure of chlorosantonin (491) obtained from santonin 4,5-epoxide with hydrogen chloride gas has been solved by X-ray analysis. Undoubtedly the most remarkable sesquiterpenoid rearrangement is that observed when the dried sodio salt of (492) is heated to reflux in excess phosphorus oxychloride. The rearrangement product in question was isolated by removal of the excess POCI3, followed by neutralization with concentrated aqueous ammonia. The resultant ether extract was treated with hot 15% sodium hydroxide and the product mixture was distilled and purified by column chromatography. One of the products (about 3% yield) has been identified by X-ray analysis as (493), but as yet no mechanism has been suggested... 

Some new eremophilane sesquiterpenoids have been identified. These include flourensic acid (351), petasalbin methyl ether (352), " furanofukinol (353 ... 

The first enantioselective total synthesis of tetracyclic sesquiterpenoid (+)-cyclomyltaylan-5a-ol, isolated from a Taiwanese liverwort, was accomplished by H. Hagiwara and co-workers. They started out from Hajos-Parrish ketone analogue, (S)-(+)-4,7a-dimethyl-2,3,7,7a-tetrahydro-6/-/-indene-1,5-dione, that could be synthesized from 2-methylcyclopentane-1,3-dione and ethyl vinyl ketone in an acetic acid-catalyzed Michael addition followed by an intramolecular aldol reaction. The intramolecular aldol reaction was carried out in the presence of one equivalent (S)-(-)-phenylalanine and 0.5 equivalent D-camphorsulfonic acid. The resulting enone was recrystallized from hexane-diethyl ether to yield the product in 43% yield and 98% ee. Since the absolute stereochemistry of the natural product was unknown, the total synthesis also served to establish the absolute stereochemistry. 

Trimethylsilyl ethers are much more volatile than usual ethers and hence well suited for gas-liquid chromatography. Thus Meinwald6 was unable to effect direct purification of an allenic sesquiterpenoid (1), the defensive substance of the grasshopper Romalea microptera however, the bistrimethylsilyl derivative was purified without difficulty by gas-liquid... 

The triol (130) has been isolated from the micro-organism Fusicoccum amy-gdali, the acid (131) from Cedrus deodara is probably a nor-sesquiterpenoid, the thymoquinol ether (132) is reported to occur in Blumea membrancea, and... 

In a later study, the aroma constituents of a Bavarian (Pilsener) beer brewed in Hallertau, near Munich, which possessed a desirable fine hop aroma, was examined [58]. Neither the terpenes and sesquiterpenes nor the methyl esters characterized in hop oil were detected but fraction IV (Table 13.6), which contained terpenoids and sesquiterpenoids, possessed an intensive pleasant hoppy odour. Noteworthy amongst the identified constituents are the cyclic ethers (80)-(86) first found in Japanese hops, the flowery notes of which contribute to hop aroma, and the sesquiterpenoids derived from humulene such as humulene epoxide I, humulene epoxide II, humulol, and humulenol II. Similar results were found with American beers [60, 86]. Humuladienone (79)... 

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