Synthesis of aminosaccharides as a core compound for constructing a solution-phase derived library

• Main Authors: Pang, Cheng-Tse, 潘承澤
• Other Authors: Yu, Chung-Shan
• Format: Others
• Language: zh-TW
• Published: 2009
• Online Access: http://ndltd.ncl.edu.tw/handle/63633126174632025710

碩士 === 國立清華大學 === 生醫工程與環境科學系 === 97 === The aim of this research is to generate the monosaccharide, disaccharide, trisaccharide and tetrasaccharide of galactose bearing amine groups which would be used for coupling with numerous carboxylic acids. The coupled products in the mixture was directly submitted to a screen assay for their cytotoxicities against the cancer cell lines. Monosaccharide Gal-O-(CH2)3CH2N3, disaccharide Gal(1→6)Gal, trisaccharide and tetrasaccharide have been successfully prepared. Glycosylation of the 2-(azidomethyl)-6- ((trichloromethylamino)methoxy)tetrahydro-2H-pyran-3,4,5-triyl tribenzoate, bearing the active leaving group of imidate, with the acceptors of galactose and lactose derivative to provide (2R,3S,4S,5R,6S)-2-(((2S,3R,4S,5S,6R)-6-(azidomethyl)-3,4,5-tris(benzoyloxy)tetrahydro-2H-pyran-2-yloxy)methyl)-6-((2R,3R,4S,5R,6S)-4,5-bis(benzoyloxy)-2-(benzoyloxymethyl)-6-(p-tolylthio)tetrahydro-2H-pyran-3-yloxy)tetrahydro-2H-pyran-3,4,5-triyl tribenzoate and (2R,3S,4S,5R,6S)- 2-(((2S,3R,4S,5S,6R)-6-(azidomethyl)-3,4,5-tris(benzoyloxy)tetrahydro-2H-pyran-2-yloxy)methyl)-6-((2R,3R,4S,5R,6S)-2-(((2S,3R,4S,5S,6R)-6-(azidomethyl)-3,4,5-tris(benzoyloxy)tetrahydro-2H-pyran-2-yloxy)methyl)-4,5-bis(benzoyloxy)-6-(p-tolylthio)tetrahydro-2H-pyran-3-yloxy)tetrahydro-2H-pyran-3,4,5-triyl tribenzoate in 70% and 63% yield, respectively. The ratio of α-form and β-form of the trisaccharide was α/β=1/9. On the other hand, a poor yield of the glycosylation of 2-(azidomethyl)-6- ((trichloromethylamino)methoxy)tetrahydro-2H-pyran-3,4,5-triyl tribenzoate, Phenyl O-(2,6-Di-O-benzoyl-3,4-O-isopropylidene-β-D- galactopyranosyl)-( 1-4)-2,6-di-O-benzoyl-1-thio-β-D-glucopyranoside and (2S,3R,4S,5R,6R)-4-acetoxy-5-((2S,3R,4S,5R,6R)-3-(benzoyloxy)- 6-(benzoyloxymethyl)-4,5-dihydroxytetrahydro-2H-pyran-2-yloxy)-6-(benzoyloxymethyl)-2-(p-tolylthio)tetrahydro-2H-pyran-3-yl benzoate was observed. This could be accounted for the steric hindrance of the second alcohol at C-3, C-3’ and C-4’ of Phenyl O-(2,6-Di-O-benzoyl- 3,4-O-isopropylidene-β-D-galactopyranosyl)-( 1-4)-2,6-di-O-benzoyl-1-thio-β-D-glucopyranoside and (2S,3R,4S,5R,6R)-4-acetoxy-5- ((2S,3R,4S,5R,6R)-3-(benzoyloxy)-6-(benzoyloxymethyl)-4,5-dihydroxytetrahydro-2H-pyran-2-yloxy)-6-(benzoyloxymethyl)-2-(p-tolylthio)tetrahydro-2H-pyran-3-yl benzoate. 2-(azidomethyl)-6-((trichloromethylamino)methoxy)tetrahydro -2H-pyran-3,4,5-triyl tribenzoate can be prepared via a 8 step synthesis in total 5% yield. The extended linker with azide group of 4-azidobutan-1-ol after hydrogenation could provide the desired core amine, (2R,3R,4S,5R,6R)-2-(4-aminobutoxy)-6-(aminomethyl)tetrahydro-2H-pyran-3,4,5-triol. It will be submitted to the library construction and the corresponding bioassay.