Cyclorelease strategy

Nicolaou, K. C. Winssinger, N. Pastor, J. Murphy, F. Solid-Phase Synthesis of Macrocyclic Systems by a Cyclorelease Strategy Application of the Stille Coupling to a Synthesis of (.S )-Zearalenone, Angew. Chem. Int. Ed. Eng. 1998, 37, 2534. 

Scheme 7.3 Intramolecular Stille coupling in macrocyclization. (a) Solution-phase synthesis [54]. (b) Solid-phase synthesis by a cyclorelease strategy [55].

Nicolaou KC, Winssinger N, Pastor J, Murphy F. Solid-phase synthesis of macrocychc systems by a cyclorelease strategy. Angew. Chem. Int. Ed 1998 37 2534-2537. 

In such linkers, the latent bond requires activation before cleavage can occur. Many of the linker units discussed elsewhere in this chapter could be considered safety-catch linker units. For example, photolytic activation described in Section 1.2.4 and cyclorelease discussed in Section 1.2.2 are essentially safety-catch strategies. This section, however, will concentrate on synthetic activation. The first example of such an approach was a sulfonamide linker reported by Kenner et al. in 1971. The sulfonamide 7 is stable to both acidic and basic conditions, making it synthetically valuable. However, alkylation of the nitrogen with, for example, diazomethane or iodoacetonitrile, gave 8, from which substrates (e.g., carboxylic acids 9) could be cleaved under nucleophilic conditions (Scheme 1.4). 

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