Ring closure macrocyclic

The Stille reaction has been successfully applied to a number of macrocyclic ring closures.207 In a synthesis of amphidinolide A, the two major fragments were coupled via a selective Stille reaction, presumably governed by steric factors. After deprotection the ring was closed by coupling the second vinyl stannane group with an allylic acetate.208... 

Compound 1 was first analyzed its possible prepaiation from of alkene 4. Further retrosynlhetic dismembering was directed toward construction of the 14-memhered macrocycle. Ring closure via macrolactami/ation represented one possibility, but that would have required selective construction of the trisubstiluted alkene 6. Hove-da regarded this synthesis as sufficiently difficult that he instead utilized an alternative cyclization. This led him to compound 5.2 The precise nature of the cyclization and the pathway to the enan-tiomerically and diaslercomcncally pure precursor molecule 5 is the subject of this chapter. 

The basic reactions which are involved in the synthesis of macrocyclic compounds are very simple and of a very few types. In this section we shall consider the basic organic chemistry of macrocyclic ring-closures and how a metal ion may activate or control these reactions. In most cases, these reactions involve the formation of heteroatom-carbon bonds. 

To make intramolecular esterification feasible it is always necessary to activate one or both interacting sites of a hydroxy acid precursor. All the methods of macrocyclic ring closure involving lactonization come from this principal idea. 

Two routes for synthesizing macrolides via olefin metathesis (WCl6/Me4Sn catalyst) have been described by Villemin one route involves the preparation of co-hydroxyacid by metathesis followed by cyclization, the second involves macrocyclic ring closure by metathesis of co,co -diunsaturated ester. 

Figure 18. Chemical template leactions a) macrocyclic ring closure b) macrobicyclization closure c) catenane formation d) tying the trefoil knot...

Stocks, M.J., Harrison, R.P and Teague, S.J. (1995) Macrocyclic ring closures employing the intramolecular Heck reaction. Tetrahedron Lett., 36, 6555-8. 

Takahashi et al. have reported on a combinatorial synthesis of a library of 122 macrosphelides, which uses a three-component coupling in which not only the building blocks are connected by a Pd-catalyzed carbonylation, but also this reaction is used for macrocyclic ring closure on a solid support (Scheme 7) [101]. 

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