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

2.2 Resuits and Disudon
2.2.1 Preparution of Bac-Ser(aLd)OBO ester
in an effort to expand the scope of the OB0 ester methodology previously
reported (Scheme 2. 18),49 we investigated expanding the various nitrogen protecting
groups to inciude the Boc group. We were patticularly interesteci in the synthesis of j3-
hydroxy-a-arnino acids for the eventual incoporation and synthesis of analogs of the
aureobasidin class of antihingal agents?
We initially attempted to overcome the dificulties associated with the
esterification of oxetane dcohol with DCC and DMAP. Although the yields for the
esterif ication were excellent (80-85%), the reaction required an excess of oxetane alcohol
and chromatography on silica to obtain a pure produd9 Trace amounts of the diimide or
urea aiso affected the yields of the BSsEt2O catalyzed rearrangement of the oxetane ester
to the OB0 ester. We found that the desired oxetane ester is much more conveniently
prepared by esterification of the N-protected senne carboxylate by the corresponding
oxetane tosylate 2.38 or bromide 2.39. The oxetane bromide 2.39 cm be prepared in a
number of ways from the 3-methyl-3-(hydroxymethyl)oxetane with
brominehnphenylphosphine," carbon tetrabromideltri-phenylphosphine5* or by
displacement of the corresponding tosylate 2.38 with sodium bromide in acetone
(Scheme 2.19). The oxetane bromide 2.39 may be distilled from these reactions but
slowly decomposes upon standing. The tosylate 2.38 was prepared using standard
conditions and then poured into a slurry of icdcold water at which point the tosylate
precipitated out and was isolated as a stable crystalline material in 90-95% yield after
filtration and drying under vacuum over PzO5.