Terpene isothiocyanates

The marine isothiocyanates, with more than 80 compounds isolated so far, form the largest group of naturally occurring isothiocyanates. This well-established group of marine natural products is constituted mainly by terpene metabolites present as sesquiterpene and diterpene derivatives. The non-terpene isothiocyanate compounds include two cylindricine alkaloids and a series of long-chain aliphatic metabolites. Marine sponges constitute the main source of these compounds, although they are also found in nudibranches and tunicates. 

The incorporation of thiocyanate into the isocyanide axisonitrile-3 (20) may indicate that A. cavernosa is able to desulphurise thiocyanate. Some enzymes, such as glutathione S-transferases and some peroxidases, can convert thiocyanate to cyanide [82-85] marine sponges are known to contain peroxidases [43]. Alternatively conversion of the terpene isothiocyanate group to an terpene isocyanide by desulphurisation could occur using an enzyme analogous to the peroxidases, but programmed to use a secondary metabolite such as (21) as substrate. 

Heating or irradiating alkenes in the presence of sulfur gives relatively low yields of thiiranes. For example, a mixture of sulfur and norbornadiene in pyridine-DMF-NHa at 110 °C gave a 19% yield of the monoepisulfide of norbornadiene as compared with a 78% yield by the method of Scheme 120 (79JCS(Pi)228). Often 1,2,3-trithiolanes are formed instead of thiiranes. The sesquiterpene episulfides in the essential oil of hops were prepared conveniently by irradiation of the terpene and sulfur in cyclohexane (Scheme 135) (80JCS(Pl)3li). Phenyl, methyl or allyl isothiocyanate may be used as a source of sulfur atoms instead of elemental sulfur. 

Subsequent epidemiological studies have supported the association between better health and long-term consumption of diets rich in foods of plant origin. " However, whether this is because such diets minimize exposure to deleterious substances (e.g., oxidized cholesterol, pyrolysis mutagens, salt, saturated fat, etc.), or maximize intake of certain beneficial nutrients (e.g., isothiocyanates and other sulfur-containing plant constituents, mono-unsaturated fatty acids, and poly-unsaturated fatty acids, PPT, poly acetylenes, selenium, terpenes, etc.) or some combination as advocated in the Polymeal concept, remains unknown. " An in vitro study indicates that there may be mechanistic basis for true synergy between PPT and isothiocyanates. ... 

A second group of bioactive sponge metabolites with an unusual structural motif are the terpene isocyanides, which often co-occur with structurally related isothiocyanates and forma-mides.157-159 Less commonly encountered nitrogenous based substituents present in sponge terpene metabolites include isocyanates, thiocyanates, and dichloroimines (carbonimidic dichlorides). The biochemistry and ecology of these unique marine metabolites have been targeted for study by numerous researchers.159 160... 

Sillen LG (1967) How have seawater and air got their present compositions Chem Br 1 291-297 Simpson JS, Garson MJ (2004) Biosynthetic pathways to isocyanides and isothiocyanates precursor incorporation studies on terpene metabohtes in the tropical marine sponges Amphimedon terpenensis and Axinyssa n.sp. J Org Biomol Chem 2 939-948... 

The Code mentions 382 synthetic additives, comprizing 69 individual flavouring substances and the following 18 chemical groups ketones, lactones, aromatic aldehydes, aromatic alcohols, esters, ethers, isothiocyanates, indole and its derivatives, fatty acids, aliphatic aldehydes, aliphatic alcohol, aliphatic hydrogen carbide aldehydes, (translation error, probably hydrocarbons), thio alcohols, thio ethers, terpene hydrocarbons, phenols, phenolethers, furfural and its derivatives. 

Compared to isocyanides and isothiocyanates, there are far fewer examples of thiocyanate (135-139), dichloroimine (= carbonimidic dichlorides 140-146), isocyanate (36, 60, 70, 71) or amine (61,63, 65-67) groups in the marine terpene literature. The isocyanates which have been isolated [18-21] are shown in Table 1 or 2 respectively because these unusually-functionalised compounds are generally isolated together with the corresponding isocyanides or isothiocyanates, however most sesquiterpene thiocyanates (e.g. (135) [8]) represent a unique structural classes for which no isocyanide or isothiocyanate representative has yet been isolated, and these are therefore listed separately in Table 3. To date, 2-thiocyanatopupukeanane (139) [10] is the only example of a thiocyanate whose carbon skeleton has also been isolated with an isocyanide substituent 2-isothiocyanatopupukeanane is a known metabolite but has not been formally characterised in the literature. Dichloroimines such as stylotellanes A and B (141) and (140) have been found in sponges together with farnesyl isothiocyanate (147), but as yet not with any isocyanides [14-17], while very few ureas and thioureas have been isolated [23, 25, 26]. For convenience, we have therefore shown separately a list of all reported isolations of thiocyanates, dichloroimines, ureas and thioureas by structural class (Table 3). 

Our results suggest thiocyanate acts as a precursor to the isocyanide moiety of marine terpenes, as well as acting as a precursor to the isothiocyanate group. This strongly suggests either (i) an interconversion between inorganic cyanide and thiocyanate and/or (ii) an equivalent interconversion at the secondary metabolite level, i.e. between (20) and... 

The formation of terpene isocyanides appears to be exclusive to the marine environment since there are as yet no reports of terpene isocyanides, isothiocyanates or formamides in the terrestrial natural product literature. The majority of terrestrial isocyano compounds are... 

As mentioned earlier, the isolation of terpene isocyanides and isothiocyanates from both sponges and nudibranchs is circumstantial evidence that the nudibranchs acquire the metabolites by dietary transfer from sponges [32, 33]. The labelling experiments reported by our group [43] and also the uptake study of the Italians [96] provide direct evidence for a transfer process. Evidence has accumulated, through the experimental work of Paul, Hay and others, that many secondary metabolites, and terpenes in particular, play a key role in the ecology of the parent sponges [105]. The proposal that nudibranchs acquire dietary terpenes for chemical defence purposes has not yet been adequately tested [87]. 

As one might expect, flavor is typically nonuniformly distributed in the plant. For example, allyl isothiocyanate is more abundant in the outer leaves than in the inner tissues of cauliflower. Freeman and Whenham [38] dissected onion bulbs separating the bulb into individual leaves and the stem. They examined each section for lach-rymator and pyruvate. They found that the dry outer scales have virtually no lachry-mator nor pyruvate but levels increase progressively in the leaves moving towards the plant center and stem. As another example, total terpenes are more concentrated in the crown of carrots than in the midsection or tip [57]. Not only is there a difference in total flavor depending upon the plant part being examined, but there may also be a difference in flavor profile [58]. Therefore, if one dissected a plant and ate different individual parts it would not be unusual to find a slightly different flavor character for each part. 

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