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

Several methods for the removal of the ortho ester protecting group have ken
reported in the literanire and may be categorized into two procedures. In the first, acid
hydrolysis is employed to ring-open the ortho ester followed by base hydrolysis to
generate the acid ( &SOmH then 1N NaOWMeQH,*a DME:H20, pH 3 with NaSO,
then LiOH,m cataiytic pyridinium PTSA in MeOWH20 then LiOHIm). The other
procedure employs tramesterification of the ring-opened octho ester, usually to a methyl
ester (with NaOMelMeOH or K&OmeOH) followed by base hydrolysis of the methyl
ester to give the deprotected acid?
1 A.2 N-Amine Protection
In developing a strategy for the synthesis of unusual amino acids from amino acid
denved OB0 ester synthons, we decided to use the benzyloxycarbonyl (carbobenzyloxy
or Cbz) and ten-butyloxycarbonyl (Boc) protecting groups.
The Cbz group was first introduced into peptide chemistry in 1932'03 and has
many advantages over other amino protecting groups. Unlike the fluorenyl-9-
ylmethoxycarbonyl (Fmoc) group, the Cbz group is stable to basic reagents, and can be
removed by catalytic hydrogenolysis or strong acid hydrolysis. The Cbz group is
probabl y the most popular of the N-protecting group and as such, its continued use allows
for the cornparison of results to previous methods of synthesis.