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

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6.2.1 Synthesis of Resin-Bod BHydroxy - fiSubstituted- a-Amino Acids
We siudied two common polymers, Wang resin and TentaGe1 PHB' resin, on
which to perfonn the sequence of nations described in detail in chapter two. Wang
resin is generally the resin of choice for SPOC due to its excellent swelling
characteristics, straightforward cleavage of substrates off the resin and low price.
TentaGe1 PHBa resin incorporates a polyethylene glycol (PEG) spacer, and as such
possess sweIIing charactenstics and reaction kinetics more typical of solution-phase
chemistry." We choose the Cbz-equivalent linker introduced by Hauske and DoeO to
attach the a-amino group since manipulation of the a-carboxylate into the OB0 ester
was necessary to prevent racemization during Grignard reaction on the serine aldehyde.
The serina1 equivalent was incorporateci ont0 the resin as the OB0 ester since
prelirninary studies indicated BF3e Et20 mediated remangement on the resin to be
problematic. Cbz-Thr-OB0 ester 6.25 was synthesized in 92% yield over two steps, in
an identical manner to that described for Cbz-Ser-OB0 ester 3.41 (Scheme 6.10). The
Cbz protecting group was easily removed from both 6.25 and 3.41 by hydrogenolysis to
give the free amino OB0 esters 6.26 and 6.27 in quantitative yield. Of note is the fact
that both 6.26 and 6.27 were stored at room temperature for over three years without lost
of optical purity, presumably due to the acid sequestering nature of the free amine.