Manzamine ring-closing metathesis

Ring-closing metathesis is now applied as the key step in many natural product syntheses. Prominent examples are the syntheses of manzamine A [15,17] and epothilone A [18] (Scheme 8). 

For manzamine A, Martin et al. developed a strategy for the construction of the eight-membered ring E [15], Pandit et al. succeeded in the formation of the 13-membered ring D [18]. The efforts culminated recently in the total synthesis of manzamine A and related manzamine alkaloids, employing the ring-closing metathesis reaction as a key step [16]. Thus, 49 is converted into 50 with a yield of 67 % (Scheme 8). 

Scheme 8. Ring-closing metathesis as the key step in the synthesis of manzamine A and epothilone A.

Coldham I, Pih SM, Rabot R. Dipolar cycloaddition and ring-closing metathesis inthe synthesis of the tetracyclic ABCE ring system of manzamine A. Synlett 2005 11 1743-54. 

The synthesis of manzamine A by Martin and co-workers using olefin metathesis - was one of the earliest demonstrations - of how this reaction could be applied as a strategy in natural product synthesis. The ring-closing metathesis in this synthesis was conducted with Schrock s molybdenum catalyst, as shown in Equation 21.8. 

Much larger rings can be constructed using RCM. Perhaps the first example of the use of ring-closing metathesis in natural product synthesis is in Martin s synthesis of manzamine 8.249, with two challenging... 

Clark, J.S., Townsend, R,( Blake, A,), Teat, S.J., and Johns, A. (2001) A concise enantioselective synthesis of the AB ring system of the manzamine alkaloids by ring-closing enyne metathesis. Tetrahedron Lett., 42, 3235-3258,... 

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