Marine isocyanides

Garson MJ, Simpson JS (2004) Marine Isocyanides and Related Natural Products -Structure, Biosynthesis and Ecology. Nat Prod Rep 21 164... 

Garson MJ, Simpson JS. Marine isocyanides and related natural products — structure, biosynthesis and ecology. Nat. Prod. Rep. 2004 21 164-179. 

A COMPARISON OF MARINE ISOCYANIDE BIOSYNTHESIS WITH TERRESTRIAL BIOSYNTHETIC PROCESSES... 

THE ECOLOGY AND BIOLOGICAL FUNCTION OF MARINE ISOCYANIDES AND RELATED METABOLITES... 

Reviews of the syntheses of marine natural products, including marine isonitriles, have appeared recently [72]. After the early synthetic challenges of the tricyclic 9-isocyanopupukeanane (76) [73, 74] and 2-isocyanopupukeanane (78) [75] were met in 1979, additional syntheses of marine isonitriles were reported during 1986-1991. These were ( )-7,20-diisocyanoadociane (95) [63], ( )-axisonitrile-1 (1) and ( )-axamide-l (3) [76], the axisonitrile-4 triad (7-9) [78], and ( )-8,15-diisocyano-ll(20)-amphilectene (96) [79], and theonellin isocyanide (85) [80],... 

Isocyanide-based MCR was also applied for the total synthesis studies of natural products containing piperazine substructure. For example, trabectedin (also known as ecteinascidin 743 or ET-743) is undergoing clinical trials for the treatment of breast, prostate, and pediatric sarcomas. Ecteinascidin 743 (2) is an extremely potent antitumor agent isolated from a marine tunicate, Ecteinascidia turbinate [12]. Eukuyama et al. developed the total synthesis of ecteinascidin 743 from a Ugi reaction [13]. The reaction of p-methoxyphenyl isocyanide 3 gave Ugi product 7, which was cyclized to DKP intermediate 8 (Scheme 1). 

Ecteinascidin 743 262 (Scheme 12.37) represents a powerful antitumor agent, which has been submitted to clinical trial. This complex polyazacydic, polyaromatic compound was isolated from the marine tunicate, Ecteinascidia turbinate [131]. A total synthesis of this natural product, which featured an Ugi four-component reaction as pivotal step, was recently reported by Fukuyama and co-workers [132]. The highly decorated phenylglycinol 263 was obtained via an asymmetric Mannich-type reaction [133], and was engaged in a multicomponent condensation process involving the protected amino acid 264, p-methoxyphenyl isocyanide 265 and acetaldehyde to afford dipeptide 266 in high yield. This com-... 

The structurally novel antimitotic agent curacin A (1) was prepared with an overall yield of 2.5 % for the longest linear synthesis. Three of the four stereogenic centers were built up using asymmetric transformations one was derived from a chiral pool substrate. Key steps of the total synthesis are a hydrozirconation - transmetalation protocol, the stereoselective formation of the acyclic triene segment via enol triflate chemistry and another hydrozirconation followed by an isocyanide insertion. For the preparation of the heterocyclic moiety of curacin A (1) the oxazoline - thiazoline conversion provides efficient access to the sensitive marine natural product. 

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... 

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. 

Structural elucidation of the terpenoid constituents of marine plants and animals has revealed the presence of several compounds whose novel structures often have chlorine, bromine, or isocyanide substituents (cf. pp. 65 and 89). 9-Isocyano-pupukeanone (273) is a recent example of a marine sesquiterpenoid isolated from a... 

A curious diterpenoid isocyanide (174) has been obtained from the marine sponge Hymeniacidon amphilecta and its structure established by X-ray analysis. Divarol acetate (175), which is related to the dolatriols, has been obtained from some marine Dolabella species. Two further trinervitene diterpenoids (176), the 2a,3a- and 2a,3/8-diols, have been isolated from the frontal glands of the termite Nasutitermes costalis. The verrucosane skeleton has been assigned to some further diterpenoids from the liverwort Mylia verrucosa. Three more... 

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 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. 

Although comparatively rare, sesquiterpenoids containing isocyanide, isothiocyanate, and formamide, groups have been isolated from species of marine sponge (cf. Vol. 5, p. 74 Vol. 6, pp. 65, 87, 89). Included in this small group are the previously reported amorphane derivatives (164a—c), and a complete account of... 

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