Bicyclo enediynes

Intramolecular [2 + 2 + 2] cycloadditions belong to the same type of valence isomerization as those of 1,5-unsaturated compounds to cyclobutanes.70 The cobalt-mediated cyclization of l-en-5-ynes stereoselectively converts enediynes directly to bicyclo[4.2.0]hexa-l,3-dienes, as single diastereomers, when a stoichiometric amount of dicarbonyl(cyclopentadienyl)cobalt is used. This cyclization90 has a high efficiency (92%). An example is the synthesis of the protoilludane framework 23 from the enediyne precursor 22.71... 

Magnus, P. Fortt, S. Pittana, T. Snyda, J. P. Synthetic and mechanistic studies on esperamicin A, and caUchanicin yj. Molecular strain ratha than jt-bond proximity determines the cycloaromatization rates of bicyclo[7.3.1]enediynes, J. Am. Chem. Soc. 1990,112,4986-4987. 

The experiment with doubly labeled [l,2- C]acetate strongly suggested that the respective C14 bicyclo[7.3.1]enediyne and anthraquinone moieties are biosynthesized separately as two different heptaketide chains derived from seven head-to-tail coupled acetate units and should be connected at a later stage. 

From the established carbon-carbon connectivities in 304a, it was proposed that a possible precursor of the bicyclo[7.3.1]enediyne substructure could be C-14 chains such as 329 or 330, or their biogenetic analog, which can be connected with the anthraquinone moiety through a Friedel-Crafts type acylation reaction to form the C-8-C-9 bond and can also cyclize to the bicycle structure through two condensation reactions to form the C-3-C-4 and C-7-C-8 bonds. Introduction of an additional acetate unit at C-5 followed by oxidative degradation to form the carboxyl group and O-methylation from methionine should occur at some point. Tentatively, a heptacar-bonyl acid such as 331 was proposed as a possible precursor of the anthraquinone moiety. Moreover, an enediyne chain such as 329 is also conceivable as a precursor of the anthraquinone portion [332]. 

Nantz, M.H., Moss, D.K., Spence, J.D. and Olmstead, M.M. (1998) Actuating cycloaromatization of a bicyclo[7.3.1] enediyne by annelation an example of inverse dependence on bridge atom hybridization. Angewandte Chemie International Edition, 37(4), 470-473. 

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