Chapter 6 - Peptide Synthesis with Minimal Protection of Side-Chain Functions

Abstract

The various degrees and modes of protection that is regarded as minimal are practiced in a substantial fraction of conventional peptide syntheses. Whether it is chosen to minimize the use of side-chain protecting groups or to employ essentially full protection, a decision must be made early on in planning a synthesis. Lengthy stepwise elongations with infrequent intermediate purification of the growing product require rather full protection of side chains throughout. This chapter discusses peptide synthesis with minimal protection of side-chain functions. Segment condensation strategies with careful purification of intermediate peptides are compatible with the full range of possibilities regarding the use of blocking groups. Side reactions occurring with the use and removal of protecting groups may be slightly better understood and more controllable than are difficulties that arise from leaving side chains unblocked. Full protection problems tend to be delayed to the end of a synthesis, involve greater risk in the final deprotection step, and may cause increased difficulties in final purification and characterization. A failure at this stage is likely to be very time consuming. Minimal protection approaches allow greater opportunities for highly discriminatory separations at intermediate stages and involve less risk at final deprotection.