Regioselective ring opening of chiral aziridine by amine nucleophiles and their applications

다국어 초록 (Multilingual Abstract)

Part Ⅰ. Preparation of enantiomerically pure diamino alcohols by regioselective ring opening reactions of aziridine-2-methanol by various amine nucleophiles.
다양한 diamino alcohols을 아지리딘 고리가 활성화 되지 않은 aziridine-2-methanol로부터 높은 수율로 얻을 수 있었다. 아지리딘 고리가 활성화 되지 않은 aziridine-2-methanol은 silyl group에 의해 활성이 되고, 이런 활성중간체의 아민 치환반응을 통해 효율적 반응이 이루어졌다.
Part Ⅱ. Practical approach to β-aminoalanine from enantiomerically pure diamino alcohol.
광학적으로 순수한 diamino alcohol은 일반적인 실험방법으로 diamino acid로 변환될 수 있다. 이 Part에서는 다양한 diamino alcohol 중에서 하나를 β-aminoalanine의 전구체인 β-amino alcohol로 효율적으로 변환하였다.
Part Ⅲ. Efficient preparation of a conformationally restricted new amino acid.
Protected aziridine-2-methanol을 TMS-I와 chiral 아민 친핵체를 사용하여 diamino alcohol을 만들고, 분자내 고리화 반응을 통하여 이중고리 화합물을 만들었다. 이 화합물을 β-aminoalanine 전구체인 구조적으로 제한된 새로운 β-amino alcohol로 효율적으로 변환되었다.

다국어 초록 (Multilingual Abstract)

Part Ⅰ. Preparation of enantiomerically pure diamino alcohols by regioselective ring opening reactions of aziridine-2-methanol by various amine nucleophiles.
Various diamino alcohols 6a~6g, 11, 12 were prepared from nonactivated aziridine-2-methanol in high yields. Nonactivated aziridine was activated by silyl group and opened by iodide regioselectively. The ring-opened intermediate 5 was trapped by amine nucleophiles.
Part Ⅱ. Practical approach to β-aminoalanine from enantiomerically pure diamino alcohol.
The enantiomerically pure diamino alcohol can be transformed into β-aminoalanine in using a literature procedure. In this part, one of various diamino alcohols 2b was efficiently transformed into the β-amino alcohol 8 as a β-aminoalanine precursor.
Part Ⅲ. Efficient preparation of a conformationally restricted new amino acid.
The protected aziridine-2-methanol was treated with TMS-I and chiral amine, then an intramolecular reaction was carried out. The protected bicyclic compounds 9a, 9b were transformed into conformationally restricted new β-amino alcohols 11a, 11b as β-aminoalanine precursors.

목차 (Table of Contents)

• CONTENTS = ⅰ
• 요약 = 1
• ABSTRACT = 2
• Part Ⅰ. Preparation of enatniomerically pure diamino alcohols by regioselective ring opening reactions of aziridine-2-methanol by various amine uncleophiles. = 3
• Ⅰ. INTRODUCTION = 4
• Ⅱ. RESULTS AND DISCUSSIONS = 9
• A. Preparation of enantiomerically pure aziridine-2-methanol. = 9
• B. Nucleophilic ring opening reaction of aziridine-2-methanol. = 10
• Ⅲ. EXPERIMENTAL SECTION = 15
• Preparation of 2(R)-N-[(S)-α-methylbenzyl]amino-3-pyrroldine-1(R)-phenylpropanol = 17
• Preparation of 2(R)-N-[(S)-α-methylbenzyl]amino-3-piperidine-1(R)-phenylpropanol = 19
• Preparation of 2(R)-N-[(S)-α-methylbenzyl]amino-3-hexamethyleneimine-1(R)-phenylpropanol = 21
• Preparation of 2(R)-N-[(S)-α-methylbenzyl]amino-3-morpholine-1(R)-phenylpropanol = 23
• Preparation of 2(R)-N-[(S)-α-methylbenzyl]amino-3-αniline-1(R)-phenylpropanol = 25
• Preparation of 2(R)-N-[(S)-α-methylbenzyl]amino-3-benzylamine-1(R)-phenylpropanol = 27
• Preparation of 3-(2(S)-hydroxymethyl-pyrrolin-1-yl)-2(R)-N-[(S)-α-methylbenzyl]amino-1(R)-phenylpropanol = 29
• Preparation of 2(S)-N-[(S)-α-methylbenzyl]amino-3-pyrrolidine-propanol = 31
• Preparation of 2(S)-N-[(S)-α-methylbenzyl]amino-3-piperidine-propanol = 33
• Preparation of 2(S)-N-[(S)-α-methylbenzyl]amino-3-hexamethyleneimine-propanol = 35
• Preparation of 2(S)-N-[(S)-α-methylbenzyl]amino-3-morpholine-propanol = 37
• Preparation of 2(S)-N-[(S)-α-methylbenzyl]amino-3-αniline-propanol = 39
• Preparation of 2(S)-N-[(S)-α-methylbenzyl]amino-3-benzylamine-propanol = 41
• Preparation of 2(S)-N-[(S)-α-methylbenzyl]amino-3-pyrrolidine-propanol = 43
• Preparation of 2(S)-N-[(S)-α-methylbenzyl]amino-3-piperidine-propanol = 45
• Preparation of 2(S)-N-[(S)-α-methylbenzyl]amino-3-hexamethyleneimine-propanol = 47
• Preparation of 2(S)-N-[(S)-α-methylbenzyl]amino-3-morpholine-propanol = 49
• Preparation of 2(S)-N-[(S)-α-methylbenzyl]amino-3-αniline-propanol = 51
• Preparation of 2(R)-N-[(S)-α-methylbenzyl]amino-3-benzylmnine-propanol = 53
• Ⅳ. REFERENCES = 55
• Part Ⅱ. Practical approach to β-aminoalanine from enantiomerically pure diamino alcohol. = 58
• Ⅰ. INTRODUCTION = 59
• A. Rearragement of N_(α)-Protected L-αsparagines with Iodobenzene Diacetate. = 59
• B. Nitrogen nucleophiles with serine-β-lactones. = 60
• C. Using cyclic sulphamidates. = 61
• Ⅱ. RESULTS AND DISCUSSIONS = 62
• A. Preparations of Enantiomerically pure diamino alcohols. = 62
• B. Preparation of a N-protected β-alaninol as a β-aminoalanine precursor. = 63
• Ⅲ. EXPERIMENTAL SECTION = 65
• Preparation of 4(S)-piperidinemethyl-N[(S)-α-methylbenzyl]-2-oxazolidinone = 67
• Preparation of 4(S)-piperidinemethyl-2-oxazolidinone = 69
• Preparation of 4(S)-piperidinemethyl-N-tert-butoxycarbonyl-2-oxazolidinone = 71
• Preparation of 2(S)-N-tert-butoxycarbonylamino-3-piperidine-propanol = 73
• Ⅳ. REFERENCES = 75
• Part Ⅲ. Efficient preparation of a conformationally restricted new amino acid. = 77
• Ⅰ. INTRODUCTION = 78
• A. Piperazine-2-carboxylic acid and piperazine-2-methanol. = 78
• B. Preparation of (2R, 5S)-and (2S, 5S)-carboxy-1,4-diaza[4.3.0]bicyclononane as a building block for the synthesis of new potential HIV protease inhibitors. = 81
• Ⅱ. RESULTS AND DISCUSSIONS = 83
• A. Preparation of N,N-orthogonally protected piperazine-2-methanol. = 83
• B. Synthesis of (2R,5S)- and (2S,5S)-2-Carboxy-1,4-diaza[4.3.0]bicyclononane. = 84
• Ⅲ. EXPERIMENTAL SECTION = 88
• Preparation of (S)-4-benzyl-1-N-[(S)-α-methylbenzyl]-2-hydroxymethylpiperidine. = 90
• Preparation of (S)-1-N-(tert-butoxycarbonyl)-4-N-(tert-butoxycarbonty)-2-hydroxymethylpiperazine. = 92
• Preparation of 3-Oxo-5(S)-tetrahydro-oxazolo[3.4.0]pyrazine-7-carboxylic acid tert-butyl ester. = 94
• Preparation of N-[(S)-α-methylbenzyl]aziridine-2(S)-methanol silyl ether. = 96
• Preparation of 3-(2(S)-hydroxymethyl-pyrrolin-1-yl)- N-[(S)-α-methylbenzyl]amino-2(S)-methanol silyl ether. = 98
• Preparation of (2S,5S)-1 -[(S)-α-methylbenzyl]-2-hydroxymethyl silyl ether-1,4-diaza[4.3.0]bicyclononane. = 100
• Preparation of (2S,5S)-1-[(S)-α-methylbenzyl]-2-hydroxymethyl-1,4-diaza[4.3.0]bicyclononane. = 102
• Preparation of (2S,5S)-1-[(S)-1-(tert-butoxycarbonyl)-2-hydroxymethyl-1,4-diaza[4.3.0]bicyclononane. = 104
• Preparation of N-[(S)-α-methylbenzyl]aziridine-2(R)-methanol silyl ether. = 106
• Preparation of 3-(2(S)-hydroxymethyl-pyrrolin-1-yl)- N-[(S)-α-methylbenzyl]amino-2(R)-methanol silyl ether = 108
• Preparation of (2R,5S)-1-[(S)-α-methylbenzyl]-2-hydroxymethyl silyl ether-1,4-diaza[4.3.0]bicyclononane. = 110
• Preparation of (2R,5S)-1-[(S)-α-methylbenzyl]-2-hydroxymethyl-1,4-diaza[4.3.0]bicyclononane. = 112
• Preparation of (2R,5S)-1-(tert-butoxycarbonyl)-2-hydroxymethyl-1,4-diaza[4.3.0]bicyclononane. = 114
• Ⅳ. REFERENCES. = 116