Eunicelline

Wittig reaction of aldehyde 148, followed by in situ intramolecular Diels-Alder reaction of intermediate 149 and desilylation, afforded eunicellin analogues 150 and 151 as 3 1 mixture (Scheme 27) <2004SL1434>. 

Figure I. The marine natural products eleutherobin (1) and eunicellin (2).

A general synthetic route toward the marine metabolite eunicellin diterpenes was developed by G.A. Molander and co-workers.The power of this method was demonstrated by the completion of the asymmetric total synthesis of deacetoxyalcyonin acetate. A tricyclic (3-keto ester intermediate was methylated in the y-position with complete diastereoselectivity using dianion chemistry and the crude product was subjected to the Krapcho decarboxylation. This was one of the rare cases when the transformation did not only remove the methoxycarbonyl group, but at the same time epimerized the newly formed stereocenter to yield a separable mixture of methyl ketones. 

In the laboratory of G.A. Molander, a general route for the synthesis of eunicellin diterpenes was developed and was applied for the asymmetric total synthesis of deacetoxyalcyonin acetate. One of the key steps was an inramolecular NHK coupling reaction between an enol triflate and an aldehyde. The cyclopentenol product was formed in high yield as a 2 1 mixture of diastereomers. The undesired diastereomer could be transformed to the desired one using a Mitsunobu reaction. 

Briarellins are a class of eunicellin diterpenes isolated from the gorgonians Pachyclavularia violacea and Briareum polyanthes [88]. 

Deacetoxyalcyonin acetate 1 and euncellin 2 are representative members of the eunicellin class of diterpenes. The synthesis of deacetoxyalcyonin acetate 2 by Gary Molander of the University of Pennsylvania (/ Am. Chem. Soc. 2004, 126, 1642) illustrates the power of intramolecular organometallic carbonyl addition for ring construction. 

The nine-membered ether ineupatolide (413) was isolated from Inula eupatoriodes <80JOC4838>. The eunicellins are metabolites of the Cladiella genus of soft coral. Many examples have been reported <94MI 927-02), and (414) is a typical member <92TLI3I7>. The marine natural product... 

Marine organisms have again continued to provide some-very unusual diterpenoids. The sea-pen, Stylatula sp., was the source of the compounds (72) and (73). X-Ray analysis has shown that cleomeolide, from Cleome icosandra, has the structure (74). A further diterpenoid related to eunicellin, ophirin (75), has been obtained from a Muricella sp. A full paper on the ether dictyoxide (76) has appeared. ... 

Enolate Formation. Molander and coworkers report a s)m-thetic route toward the marine metabolite eunicellin diterpenes... 

Eunicellanes and (infrequently) asbestinanes are diterpenes of marine origin, including eunicelline from the alga Eunicella stricta and cladielline found in some Cladiella species. Asbestinanes such as (-)-asbestinine 2 are characteristic of the gorgonia Briareum asbestinum (Araceae). 

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