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

4.423 Me~yl-(2S)-2-[[(be11zgIo~~nyI](methyl)~o 1-1-(4-methy l-2,6,7-tri-
0~bi~y~i0[2.22]0ctt-l-y1)pe11tan~~ Cbz-N-MeL-Glu(yMe)(OMe)OBO ester
4.89/4.90.
Cbz-L-Glu(y-Me)(OMe)OBO ester 4.73 (61 mg, 0.15 mmol) was dissolved in dry THF
(5 mL) and then transferred via cannula to a second flask containing LDA (0.45 mL, 0.45
rnmol) in dry THF (3 mL) at 40°C. After one hour, Me1 (38 pL, 0.75 rnmol) was added
and the mixture allowed to w m to room temperature. After 4 hours, the mixture was
poured into ether (25 mL) and extracted with 3% NWl (10 mL), 10% NaHC03 (10
mL), brine (10 mL) and diied over MgS04. The solvent was removed under reduced
pressure to give a light yellow oil which was purifieci by flash chromatography (1: 1,
Et0Ac:Hex) to give a clear oil as a mixture of cis 4.89 and tram 4.90 isomers in 54%
yield (32 mg).
TU3 (1: 1, EtOAc:Hex), Rf = 0.58; 'H NMR (Acetone-&, 3 0 MHz) 6 7.42-7.26 (m, SH,
ArH), 5.09 (s, 2H, CbzCH20), 4.44 (dd, 0.53H, J = 3.4, 12.2Hz, a-CH cidtrans), 4.28
(dd, 0.47H, J = 3.4, 12.2Hz7 a-CH cidtrans), 3.86 (s, 6H, OB0 ester C m), 3.55 (s,
1.4 1 H, C02CH3 cidtrans), 3.53 (s, 1.59H, C02CH3 cidtrans), 2.72 (s, 1.5H, N-Ca), 2.69
(S. 1SH. N-CH3), 2.30-2.20 (m. lH, ')"CH), 2.11-1.98 (m, lH, B-CHH), 1.64-1.52 (m.
lH, p-CHH), 1.08 (d, 1.59H, J = 6.8Hz, yCH3 cidttans), 1.02 (d, 1.41H, J = 6.8Hz, y-
CH3 cidtrans), 0.76 (s, 3H, OB0 ester CC&); "C NMR (Acetone-&, 75 MHz) 6 175.9
210