Abstract
Aggregation due to hydrogen-bonded interchain association is thought to be the cause of difficult sequences in solid-phase peptide synthesis. Hmb (2-hydroxy-4-methoxybenzyl) was introduced recently as a backbone-protecting group for Fmoc/tBu strategies which inhibits this association. Hmb derivatives of four amino acids are now available commercially. This paper describes the syntheses of two difficult sequences which were achieved by judicious use of the Hmb protecting group. (Hmb)Gly, which is attractive because of the ease of coupling the following residue, did not always produce the expected long-range effect. Moving the Hmb protection to a suitable preceding position in the sequence overcame this shortcoming.

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