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

"
6.29
NMM, CH&
Scheme 6.11
The arnino acid denvatives 6.26 and 6.27 were coupled to the resin in the
presence of N.0-bis(trimethysi1yl)acetarnide (BSA) and DMAP to give the resin-bound
amino acid OB0 esters 6.32 and 6.33. After 36 h, the remaining reactants were
thoroughly washed off the resin with DMF and CH2Q till the rinsing was clear.
Loading was determined by either elemental analysis or in the case of 6.31, the rinsings
combined, reduced in volume then assayed using spectrophotometric techniques for p-
nitrophenol content. Substitution generally occurred in ~ 95% yield but varied from batch
to batch. The resin was then capped by rinsing with copious amounts of methanol, rinsed
with Et20 then dried under vacuum.
The progress of reactions could be monitored by a number of techniques specially
developed for SPOC. FT-IR is particularly useful due to changes in functional groups.
For exarnple, 6.31 to 6.32 is charactenzed by a 1761 cm-' to 1720 cm" shifi. MAS-NMR
was used when pronounced changes occurred in the 'H NMR, such as the appearance of
the OB0 ester CH2-O in 6.32 using a 2D TOCSY.)' spin-echon or presaturation pulse
experimen t (Figure 6.2).33