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

equires carefiil attention to prevent any contaminating acetic acid which hyàrolyzes the
OB0 ester.
Both Boc-Ser-OB0 ester 2.44 and Boc-Thr-OB0 ester 2-45 have been stored for
over one year at room temperature with the slow loss of opticd activity, primarïly due to
OB0 ester ring opening. Aldehyde 2.46 tends to rapidly lose its optical activity due to
racemization even when stored at -20°C.
2.2.2 Addition of Various Grignard Reagents to Boc-Serfa1d)OBO ester 2.46 and Boc-
Thr(ket)OBO ester 2.47.
In order to investigate the suitability of Boc protected amino acids to the
conditions required for the synthesis of OB0 ester protected p-hydroxy-a-amino acids,
we first examined the Grignard addition of methylmagnesium halides to Boc-
Ser(ald)OBO ester 2.46 since the products would correspond to threonine and affo-
threonine. Standards are available for d l four diastereomers (L- and D-threonine and L-
and D-allo-threonine or 2S,3R; 2R,3S; 2S,3S; îR,3R respectively) and therefore the
stereoselectivity and extent of racemization could be monitored.
A variety of conditions, based on earlier experience, were examined (Table 2.1):'
Typically, the Grignard reagent (3 equivalents) was added quickly to a sotution of the
ddehyde 2.46 at the appropriate temperature (Scherne 2.2 1). Reaction times generally
varied from 0.5-2 hours and the progress of the reaction monitored by TLC. The reaction
mixture was quenching by pouring into cold 3% -1 after a TLC indicated no further
progression in the reaction. The yields for al1 reactions in Table 2.1 are reported for the
two step procedure fiom Boc-Set-OB0 ester 2-44 (Swem oxidation then Grignard
reaction) since the cade ddehyde was generally used without M e r purification.