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

1.3.4.1 Fonnylglycine Equivalents ...................................................-.................... 20
1.3.4.2 Alanine /%Anion Equivalents ................................................................ 23
1.3.4.3 Alanine SCation Equivalents ................................................................. 2 4
1.4 Description of Thesis ................................................................................................. 28
1.4.1 Ortho Esters ...................................................................................................... 29
1.4.2 N-Amine Protection .............. .,. ........................................................................ 31
1.5 References .................................................................................................................. 33
Chapter Two
Synthesis of Boc Proteeteci B-Hyàroxy-a-Amino Acids
2.1 Introduction ............................................................................................................... 43
2.1.1 Synthesis of PHydroxy- a-Amino Acids; General Routes .................................. 45
2.1.2 Synthesis of Racemic SHydroxy-. a.Amino Acids .............................................. 45
2.1.3 Synthesis of Optically Active PHydroxy-a-Amino Acids .................................. 46
2.1.3.1 Entymatic Synthesis of PHydroxy- a-Amino Acids ................................ -46
2.1.3.2 Enantioselective Reductions ..................................................................... 47
.......................................................
2.1.3.3 Electrophili~ucleophilic Amination 49
2.1.3.4 Synthesis jhm Glycine Enolates ........................................................... 52
2.1.3.5 Synthesis fLom a-Amino Acids ................................................................. 55
2.2 Results and Discussion ............................................................................................. 58
2.2.1 Preparation of Boc-Ser(a1d)OBO ester 2.46 ..................................................... 58
2.2.2 Addition of Various Grignard Reagenis tu Boc-Ser(ald)OBO ester 2.46
and Boc-Thr(ket)OBO ester 2.47 ....................................................................... 61
2.2.3 Deprotection of /%Dialkyl- ad /%Hydroxy-a-Amino Acids .............................. 66
2.2.3.1 BOC Removal .............................................................................................. 66
2.2.3.2 Ortho Ester Cleavage ............................................................................... 67
2.2.3.3 Purification Methodr ................................................................................ 68
2.2.4 Determination of Enantiomeric Pun'iy by HPLC Amlysis ................................ 69
2.2.5 Stereoselectivi~ of Carbonyl Additions to Boc-Ser(ald)OBO ester 2.46
and Boc-Thr(ket)OBO ester 2.47 .................................................................... 70
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