Orthogonal deprotection

Scheme 11.9 Orthogonal deprotection strategy for the preparation of carbohydrate cores.

The reactions in Scheme 70 illustrate the fact that —MOM acetals lie between —OMe and —OCON(Pr-i)2 groups in their directing ability. Orthogonal deprotection conditions (acid for MOM, base for the carbamate) makes MOM and OCON(Pr-i)2 a useful pair of directors for the regioselective synthesis of substituted phenols and aryl ethers. 

The majority of cyclic peptides synthesized on solid support are cyclized in the head-to-side-chain or side-chain-to-side-chain mode. For this purpose the amino acids involved in cyclization must be side-chain protected in a manner that allows for an additional level of orthogonal deprotection. Thus, upon assembly of the fully protected linear precursor on-resin, deprotection of the functionalities involved in the lactam ring formation is performed, followed by regio-selective cyclization by amide bond formation, and finally by the resin-cleavage/deprotection step as outlined in Scheme 16. In Table 8, examples of syntheses of such cyclic peptides are listed with the relevant information regarding protection scheme, resin anchor, and mode of cyclization. 

B. Orthogonal deprotection of Fmoc O-glycopeptide tert-butyl... 

A. Orthogonal Deprotection of Fmoc O-glycopeptide Benzyl Esters... 

Smith, A.B. Jill, Savinov, S.N., Manjappara, U.V. and Chaiken, I.M. (2002) Peptide-small molecule hybrids via orthogonal deprotection-chemoselective conjugation to cysteine-anchored scaffolds. A model study. Organic Letters, 4, 4041—4044. 

The appeal of cyclic peptides as a rich source of biologically active molecules makes the synthesis of combinatorial libraries of these compounds desirable. However, few avenues for the synthesis of large arrays of cyclic peptides exist. This is primarily caused by the difficult orthogonal deprotection requirements, which require a careful choice of synthetic strategy. For example, if a solution-phase head-to-tail cyclization is undertaken (15) (Fig. 2A), the peptide must be purified at each step of the synthesis (i.e., after synthesis of the linear, cyclized protected and after deprotection) (see Note 1). 

Is it possible to use several of these photoactivatable groups in one molecule for orthogonal deprotection by wavelength-selective cleavage First attempts with various nitrobenzyl group derivatives were only partially successful mainly because of energy transfer between the chromophores [42, 43]. 

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