The synthesis of variant 2c possessing the medium-sized trisubstituted AA Z-Abu required coupling of dipeptides 4 and 11, which was a challenging reaction (Scheme 3). Brief attempts at optimization revealed that HBTU could promote the coupling in low but consistent yields. While it is possible that either protecting the secondary alcohol of 11 or inverting the order of the dehydration and coupling steps could have resulted in better yields, we elected not to explore these alternatives since we were able to generate the required amounts of 2c using the short sequence shown in Scheme 3. This peptide was produced in modest yield by dehydrating tetrapeptide 12 with the Martin sulfurane. 22a