Eunicellin diterpenes

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]. 

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

Enolate Formation. Molander and coworkers report a synthetic route toward the marine metabolite eunicellin diterpenes (eq 71). Treatment of a tricyclic -keto ester intermediate with BuLi and subsequent y-methylation occur with complete diastereoselectivity the concluding Krapcho reaction not only removes the methoxycarbonyl group, but also effects epimerization of the newly formed stereogenic center. A subsequent epoxide intermediate is reduced using Sharpless reagent (WCl /BuLi) to provide the required olefin. ... 

Chill, L., Berrer, N., Benayahu, Y, and Kashman, Y. (2005) Eunicellin diterpenes from two Kenyan soft corals./. Nat. Prod., 68,19-25. 

Molander, GA., St Jean, D.J., and Haas, J. (2004) Toward a general route to the eunicellin diterpenes the asymmetric total synthesis of deacetoxyalcyoninacetate./. Am. Chem. Soc., 126,1642-1643. 

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. 

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). 

Ortega MI, Zubia E, Salva J. Stracture and absolute configuration of palmonine F, a new eunicellin-based diterpene fiom the gorgonian eunicella verrucosa. J. Nat. Prod 1994 57 1584-1586. 

Quayle employed an ATRC to approach the eunicellin core, a diterpene isolated from soft corals off the coast of Banyuls-sur-Mer. Treatment of geraniol trichloroacetate 29 with the copper catalyst induced cyclization to yield lactone 30 in 72% yield (Scheme 25.14). The monocyclic lactone is formed at room temperature, but then harsher reaction conditions (84°C) are required because of the less activated nature of the a-dichloro moiety of 31. The resulting dia-stereoisomeric chlorides undergo spontaneous dehydrochlorination to give 32 as a 2 1 diastereoisomeric mixture at carbon ( ). 

Briarellins J-P and polyanthellin A New eunicellin-based diterpenes from the gorgonian coral Briareum polyanthes and their antimalarial activity./. Nat. Prod., 66, 357-363. 

Uchio, Y, Nakatani, M., Hase, T., Kodama, M Usui, S., and Fukazawa, Y. (1989) A new eunicellin-based diterpene from an Okinawan soft coral, CladieUa sp. Tetrahedron Lett., 30, 3331-3332. 

Holmes examined the use of catalyst 186 and its enantiomer in the intramolecular cycloaddition reaction of enal 191 (Scheme 17.26) [102]. When the cycloaddition was conducted in the presence of 186, exo diastereomer 193 was formed in 67 % yield (dr > 95 5). In contrast, when enf-186 was employed as catalyst, endo adduct 192 was isolated in 62 % yield and dr= 15 1. Product 193 functioned as a key intermediate en route to the diterpene eunicellin (194). 

---