Dienediynes synthesis

Enediynes with ethylene carbonate fragment in the synthesis of dienediyne models of the biradical-forming and DNA-cleaving natural neocarzinostatin chromophore 99SL657. 

Suffert J, Toussaint D (1997) Synthesis of a Cyclic Dienediyne Related to the Maduropeptin Chromophore. Tetrahedron Lett 38 5507... 

From a tactical perspective, early retrosynthetic removal of the epoxy dienediyne core must dominate all synthetic planning for (+ )-neocarzi-nostatin, since its presence in any intermediate will render that molecule highly susceptible to nucleophilic attack, and will jeopardise the success of all the remaining chemistry. In essence, it would be strategically advisable to install the epoxy dienediyne unit late in a forward total synthesis of ( + )-neocarzinostatin. 

However, in another contribution, Chung and coworkers realized the one-pot synthesis of [ S.5.5.6] fenestranes 42 via intramolecular cobalt-catalyzed tandem Pauson-Khand/Diels-Alder reactions of dienediynes 41 [44] (Scheme 21). 

Scheme 5-2 Synthesis of unsymmetrical cyclic dienediyne 53 by stepwise cross-coupling reactions.

Workers from Hoffmann-La Roche have also devised a linear synthesis of racemic LTA4 methyl ester during the course of a synthesis of LTE4. They too employed a sulfonium salt (Scheme 3.22) in the epoxide-forming step to obtain a dienediyne epoxide. This step was made reasonably efficient by the use of a two-phase reaction system with a phase-transfer catalyst. Their sequence is also amenable to reasonable scale-up as they describe the preparation of 18 g of the epoxide mixture in a single reaction. A unique aspect of this synthesis is... 

Scheme 7-20 Synthesis of the epoxy dienediyne core of NCS chiomophore (Myers et al.).

A synthesis of dienediynes from 2-(hydroxymethylene)cyclopentanone involves the di-enol ditriflate [bis(trifluoromethanesulphonate)] 120, which reacts with an alkyne in the presence of a palladium catalyst to give 121, accompanied by only small amounts of the regioisomer 122. The major product on treatment with the same or different alkyne yields the dienediyne 123 2-(Alkyn-l-yl)-l-methylpyrrolidines 125 (R = Me, pentyl, MesSi or Ph) have been obtained from the thiolactam 124 by sequential alkylation, treatment with a lithium acetylide and reduction with LAH. The phenylthio group in a-(phenylthio)-lactams is displaced by an alkynyl group by the action of an alkyn-l-ylzinc chloride or of di(alkyn-l-yl)zinc compounds. Thus the j -lactam 126 gave 127 and the azaprostacyclin II 128 gave 129 1... 

The enediyne core structure of the neocarzinostatin chromophore has been ass -bled by combining an intramolecular carbopalladation starting from a bromoenediyne (Scheme 24, Eq. or a 1,1-diiodoenediyne with a subsequent Stille coupling (Scheme 24, Eq. The latter synthesis of a dienediyne starting from the diiodoenediyne... 

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