Solid phase peptide synthesis basic strategies

The 2-[(4-nitrophenyl)sulfonyl]ethoxycarbonyl group (Nsc, 27) has been developed as an alternative to the Fmoc group for solid-phase peptide synthesis,t 9 to counter certain shortcomings of the Fmoc/tBu strategy such as the insufficient stability of N -Fmoc-pro-tected amino acids and peptides in weakly basic conditionst 1 and unfavorable hydro-phobic interactions and steric hindrance of the bulky Fmoc group. 

Silyl ethers of hydroxy amino acids have been employed in both solid-phase and solution peptide synthesis. Since the TBDMS and TBDPS ether groups are stable to piperidine and other basic reagents, these derivatives of Ser and Thr (Tables 8 and 9) can be used in the Fmoc strategy.Homodetic peptides and depsipeptides have also been synthesized using TBDMS hydroxy protection for phenyllactic acid and hydroxyisovaleric acid, respectively. 

Dipyridyl disulfide and related compounds have also been used as a method for macrolide formation the addition of thio-philic metal cations and/or pyridine derivatives has been found to assist this process. This oxidation-reduction condensation, using 2,2 -dipyridyl disulfide, constitutes an excellent strategy for the solid-phase synthesis of peptides. This method does not affect amino acids sensitive to oxidation, proceeds under mild conditions without the requirement of basic or acid catalysts, and has the advantages of minimizing both racemization of carboxyl component and side-reactions of certain amino acids. Furthermore, it has been successfully applied to phosphorylation reactions, such as the synthesis of coenzyme A, oligothymidilates, and nucleotide cyclic phosphates, and nucleotides from G ,2 -cyclouridine. ... 

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