Orthogonal protecting group

The usefulness of this family of protecting groups has been proved in countless applications, both in the total synthesis of natural products, where protecting group orthogonality is often a critical issue (e.g., in the total synthesis of Calicheamycin [ 15] or Aplysiatoxin [16] Scheme 13.3) or in the light-directed synthesis of oligonucleotides (DNA-chips) [17]. 

Asp and Glu are often incorporated for the formation of lactam-bridged peptides. In this case, a protecting group orthogonal to those normally used in SPPS must be used. The palladium-sensitive allyl (OAl) group is compatible with both Boc and Fmoc, chemistries [17-19]. The side-chain... 

In all cases examined the ( )-isomers of the allylic alcohols reacted satisfactorily in the asymmetric epoxidation step, whereas the epoxidations of the (Z)-isomers were intolerably slow or nonstereoselective. The eryfhro-isomers obtained from the ( )-allylic alcohols may, however, be epimerized in 95% yield to the more stable tlireo-isomers by treatment of the acetonides with potassium carbonate (6a). The competitive -elimination is suppressed by the acetonide protecting group because it maintains orthogonality between the enolate 7i-system and the 8-alkoxy group (cf the Baldwin rules, p. 316). 

Developments of protection strategies in peptide synthesis have led to the introduction of a wider variety of protecting groups for different functionalities and provide orthogonal protection to specific side chains (Table 1). 

Scheme 11.11 A structure formed using a one-pot method with orthogonal protecting groups.

FIGURE 5.13 Protecting group combinations employed in solid-phase synthesis. The protector written in italics is removed after each residue is incorporated into the chain. (A) Boc/Bzl3 is not an orthogonal system — all substituents are removed by acidolysis. (B) Fmoc/tBu27 [Atherton et al., 1978] is an orthogonal system - Fmoc is removed by P-elimi-nation, other substituents by acidolysis. More suitable variants of the side-chain protectors are also used. 

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