Sesquiterpene isocyanides

Dumdei, E. J., Flowers, A. E., Garson, M. J., and Moore, C. J., The biosynthesis of sesquiterpene isocyanides and isothiocyanates in the marine sponge A canthella cavernosa (Dendy) evidence for dietary tranfer to the dorid nudibranch Phyllidiella pustulosa, Comp. Biochem. Physiol., 113A, 1385, 1997. 

Compounds containing the isocyano group have fascinated natural products chemists ever since the first isocyanide xanthocillin was isolated from the fungus Penicillium notatum Westling in 1950 [1]. The existence of sesquiterpene isocyanides was first reported from the Mediterranean sponge Axinella cannabina in 1973 [2], closely followed by sesquiterpene isocyanides from the Mediterranean sponge Acanthella acuta by Minale et al. [3] and the Hawaiian sponge Halichondria sp. by Scheuer et al. [4]. These early reports also documented the presence of isothiocyanate [2] and formamide [4] functionality attached to the same carbon nucleus as the... 

Table 1 provides an update of the Chang-Scheuer summary and lists the structures of all new marine sesquiterpene isocyanides and related compounds including isothiocyanates, (1 - 67), by compound class,... 

Table I Isolation of Sesquiterpene Isocyanides, Isothiocyanates, Formamides and...

Fusetani, N., Wolstenholme, H.)., Shinoda, K., Asai, N., Matsunaga, S., Onuki, H., and Hirota, H. (1992) Two sesquiterpene isocyanides and a sesquiterpene thiocyanate from the marine sponge Acanthella cf. cavernosa and the nrrdibranch PhyUidia oceUata. Tetrahedron Lett., 33, 6823-6826. 

Pais, M., Fontaine, C., Laurent, D., La Barre, S., and Guittet, E. (1987) Stylotelline, a new sesquiterpene isocyanide from the sponge... 

The electron is the smallest thinkable nucleophile which—generated from lithium in ethylamine—is even able to open certain unactivated vinylcyclopropanes (equation 142) the spiro[4.5]decane so obtained could be converted into the isocyanide sesquiterpene (— )-axisonitrile-3, which has the opposite absolute configuration of a marine sponge constituent . ... 

In the laboratory of T.-L. Ho, the total synthesis of the novel marine sesquiterpene (+)-isocyanoallopupukeanane was completed." In the endgame of the synthesis, it was necessary to install the isocyano group onto the tricyclic trisubstituted alkene substrate so that it will occupy the more substituted carbon atom (according to Markovnikov s rule). The Ritter reaction was chosen to form the required carbon-nitrogen bond. The alkene substrate was dissolved in glacial acetic acid and first excess sodium cyanide followed by concentrated sulfuric acid was added at 0 °C. The reaction mixture was stirred at ambient temperature for one day and then was subjected to aqueous work-up. The product A/-alkyl formamide was subsequently dehydrated with tosyl chloride in pyridine to give rise to the desired tertiary isocyanide which indeed was identical with the natural product. 

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). 

Using the triflic anhydride method, the biomimetic theonellin isocyanide has been synthesized from its formamide in 89% yield [1238]. Theonellin is a marine sesquiterpene. 

A new sesquiterpene skeleton has been identified in an isocyanide isolated from Phillidia varicosa, and the name pupukeanane (after the locality where the molluscs were obtained) has been suggested for this carbon framework. X-Ray analysis of the crystalline phenylthiourea derived from 9-isocyanopupukeanane (4) established the structure. The structure of stemarin tosylate reveals a new diterpene skeleton (5). Crystal structures reported for various other bridged carbocyclics are reported in other, more appropriate, chapters of this volume. 

Mayol, L., Picciali, V, and Sica, D. (1987a) Nitrogenous sesquiterpenes from the marine sponge Acanthdla acuta three new isocyanide-isolhiocyanate pairs. Tetrahedron, 43, 5381-5388. 

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