Solution and Solid Phase Synthesis of Unusual a-Amino Acids From

One of the challenges of soiid-phase organic chemistry (SPOQ is the monitoring
of reactions on the solid phase. Classical meihods, such as TLC, are obviously
incompatible with resin-bound synthons, and as such a number of specialized techniques
have been devel~ped.~ These include single-bead IT-IR and magic angle spinning NMR
(MAS-NMR) as well as a number of pulse programs that take advantage of the difference
in relaxation rates between the resin and the "epitope" of interest. However, rather than
provide a detailed review of the field of combinatorial chemistry and al1 of its
peculiarities, a few key points of particula. relevance to the solid phase synthesis of
unusual a-amino acids will be discussed. Readers are directed to the following excellent
references by Wilson and C~arnik,~ Dolle4 and BaldinoS for fùrther reading.
In order to exploit the benefits of solid-phase organic chemistry (SPOC), solution
phase organic reactions should be shown to possess the same characteristics on the soïid-
phase. Having described the synthesis of various B-hydroxy-a-amino acids in some
detail: we attempted to transfer the synthetic methodology ont0 the solid-phase as
described in this chapter.
6.1.1 Solid-Phase Synthesis of a-Amino Acids
Considering that solid-phase organic chemistry was bom from the synthesis of
peptides on the solid phase first reported by Memfield,' remarkably few syntheses of
unusual a-amino acids on the solid phase have been reported, especially since the
therapeutic value of amino acid based hgs is well d~cumented.~ a-Amino acids are
also useful intermediate chiral building blocks and have been used toward the synthesis
of peptide^,^ small rnolecule combinatorial librariesI0 and as components in condensation