4∶5,7∶8-二异亚丙基-3-去氧-D-甘露-2-辛酮酸(Kdo)甲酯及其对甲基硫苷合成
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摘要
以D-甘露糖和L-酒石酸二甲酯为原料合成4∶5,7∶8-O-二异亚丙基-3-去氧-D-甘露-2-辛酮酸甲酯及其对甲基苯硫苷衍生物。首先,D-甘露糖通过缩酮反应制得2∶3,5∶6-O-二异亚丙基-D-甘露糖1;然后,L-酒石酸二甲酯2经过氧化水解,磷酰化和硅烷基化制得磷酸酯4。化合物1和磷酸酯4经Wittig-Horner反应缩合得到化合物5,脱除硅基制得4∶5,7∶8-二异亚丙基-3-去氧-β-D-甘露-2-辛酮酸甲酯6,总收率为34%。化合物6通过端基乙酰化和硫取代反应得到硫苷衍生物8,六步总收率为26%。产物结构经NMR和HRMS确证。
A synthesis method was described for Methyl 4,5∶7,8-di-O-isopropylidene-3-deoxy-D-manno-oct-2-enosonate and its thioglycoside derivatives by using D-Mannose and Dimethyl L-tartrate as the raw material. Firstly,2∶3,5∶6-di-O-isopropylidene-mannofuranoside (1) was synthesis from D-mannose by ketal reaction. At the same time,phosphate (4) was synthesized from Dimethyl L-tartrate by a three-step reaction of oxidation,phosphorylation andsilylation. Then,the Methyl 4,5∶ 7,8-di-O-isopropylidene-3-deoxy-D-manno-oct-2-enosonate (6) in total yield of 34% was obtained by Wittig-Horner reaction between compound (1) and phosphate (4),following by desilylation. The thioglycoside (8) was synthesized by acetylation and thioglycosylation of the anomeric hydroxyl group of compound (6),the overall yield was up to 26%. The structure is confirmedby NMR and MS.
A synthesis method was described for Methyl 4,5∶7,8-di-O-isopropylidene-3-deoxy-D-manno-oct-2-enosonate and its thioglycoside derivatives by using D-Mannose and Dimethyl L-tartrate as the raw material. Firstly,2∶3,5∶6-di-O-isopropylidene-mannofuranoside (1) was synthesis from D-mannose by ketal reaction. At the same time,phosphate (4) was synthesized from Dimethyl L-tartrate by a three-step reaction of oxidation,phosphorylation andsilylation. Then,the Methyl 4,5∶ 7,8-di-O-isopropylidene-3-deoxy-D-manno-oct-2-enosonate (6) in total yield of 34% was obtained by Wittig-Horner reaction between compound (1) and phosphate (4),following by desilylation. The thioglycoside (8) was synthesized by acetylation and thioglycosylation of the anomeric hydroxyl group of compound (6),the overall yield was up to 26%. The structure is confirmedby NMR and MS.
引文
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6黄家声.β-Kdo乙硫苷供体的合成[J].合成化学,2016,24(5):442-444Huang Jiasheng.Synthesis ofβ-Kdo ethionine donor[J].Chinese Journal of Synthetic Chemistry,2016,24(5):442-444
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8宋秀美,汪朝阳,李建晓,等.N,N'-二-[5-甲氧基-3-溴-2(5H)-4-呋喃酮基]-1,2-乙二胺的合成及其晶体结构(英文)[J].化学研究与应用,2009,21(8):1163-1167Song Xiumei,Wang Chaoyang,Li Jianxiao,et al.Synthesis of N,N'-di-[5-methoxy-3-bromo-2(5H)-4-furanone]-1,2-ethanediamine crystal structure(English)[J].Chemical Research and Applications,2009,21(8):1163-1167
9 Jin F.New conjugated organic dyes with various electron donors:oneand two-photon excited fluorescence,and bioimaging[J].Dyes&Pigments,2014,109(10):42-53
10 Pokorny B.First and stereoselective synthesis of anα-(2→5)-linked disaccharide of 3-deoxy-d-manno-oct-2-ulosonic acid(Kdo)[J].European Journal of Organic Chemistry,2015,17(1):110-113
11 Kragl I.New synthetic applications of sialic acid aldolase,a useful catalyst for KDO synthesis.Relation between substrate conformation and enzyme stereoselectivity[J].Cheminform,2015,25(15):119-124
12 Meguro H.Strategy and design of novel reagents for the fluorometric analysis of biomolecules[J].Journal of the Agricultural Chemical Society of Japan,2014,60(12):1919-1924
2 Hasegawa B Y,Taylor D,Ovchinnikov D A,et al.Variability of gene expression identifies transcriptional regulators of early human embryonic development[J].Plos Genetics,2015,11(8):1-32
3 Ikhdair S M.Mass spectra of heavy quarkonia and bcdecay constant for static scalar-vector interactions with relativistic kinematics[J].International Journal of Modern Physics A,2005,20(28):6509-6531
4 Chen T Y,Chao C S,Mong K K,et al.Ultrasonication-assisted spray ionization mass spectrometry for on-line monitoring of organic reactions.[J].Chemical Communications,2010,46(44):8347-8349
5 Kumar V,Tanenbaum S W,Flashner M.Chem Inform Abstract:Synthesis of glycal neuramini dase inhibitors.part ii.methyl 5-acetamido-2,6-anhydro-2,3,5-triideoxy-d-manno-non-2-en-4-ulosonate.[J].Cheminform,1983,14(1):311-317
6黄家声.β-Kdo乙硫苷供体的合成[J].合成化学,2016,24(5):442-444Huang Jiasheng.Synthesis ofβ-Kdo ethionine donor[J].Chinese Journal of Synthetic Chemistry,2016,24(5):442-444
7 Meguro H.Strategy and design of novel reagents for the fluorometric analysis of biomolecules[J].Journal of the Agricultural Chemical Society of Japan,2014,60(12):1919-1924
8宋秀美,汪朝阳,李建晓,等.N,N'-二-[5-甲氧基-3-溴-2(5H)-4-呋喃酮基]-1,2-乙二胺的合成及其晶体结构(英文)[J].化学研究与应用,2009,21(8):1163-1167Song Xiumei,Wang Chaoyang,Li Jianxiao,et al.Synthesis of N,N'-di-[5-methoxy-3-bromo-2(5H)-4-furanone]-1,2-ethanediamine crystal structure(English)[J].Chemical Research and Applications,2009,21(8):1163-1167
9 Jin F.New conjugated organic dyes with various electron donors:oneand two-photon excited fluorescence,and bioimaging[J].Dyes&Pigments,2014,109(10):42-53
10 Pokorny B.First and stereoselective synthesis of anα-(2→5)-linked disaccharide of 3-deoxy-d-manno-oct-2-ulosonic acid(Kdo)[J].European Journal of Organic Chemistry,2015,17(1):110-113
11 Kragl I.New synthetic applications of sialic acid aldolase,a useful catalyst for KDO synthesis.Relation between substrate conformation and enzyme stereoselectivity[J].Cheminform,2015,25(15):119-124
12 Meguro H.Strategy and design of novel reagents for the fluorometric analysis of biomolecules[J].Journal of the Agricultural Chemical Society of Japan,2014,60(12):1919-1924