Synthesis of lactam and acetamido analogues of sialyl Lewis x tetrasaccharide and Lewis x trisaccharide
Synthesis of lactam and acetamido analogues of sialyl Lewis x tetrasaccharide and Lewis x trisaccharide
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DOI：
10.1021/jo981204p
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发表时间：
1998-12-11
影响因子：
3.6
通讯作者：
Magnusson, G
中科院分区：
文献类型：
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作者：
Ellervik, U;Grundberg, H;Magnusson, G
二醇受体对甲氧基苯基6-O-苄基-2-脱氧-2-四氯邻苯二甲酰亚氨基-β-D-吡喃葡萄糖苷（15）与供体乙基3，4-二-O-乙酰基-6-O-苄基-2-脱氧-2-[[（2，2，2-三氯乙氧基）羰基]氨基]-1-β-D-吡喃半乳糖苷（14），4-甲基苯基2，3-二-O-乙酰基-4-叠氮基-6-O-苄基-4-脱氧-1-硫代-β-D-吡喃半乳糖苷（30）和4-甲基苯基2-O-乙酰基-4-叠氮基-6-O-苄基-4-脱氧-3-O-（甲氧基乙酰基）-1-硫代-β-D-吡喃半乳糖苷（44）分别得到乳糖-二胺衍生物16、33和45。16和33（17和34）的NHAc衍生物与供体18的岩藻糖基化，在脱保护和N-乙酰化后，分别得到2-NHAc-Le（x）和4-NKAc-Le（x）三乙酰基3和5。从四糖中间体23中除去Troc基团，然后进行N-乙酰化（-->24），得到NHAc-SLe（x）四糖2。部分保护的三糖二醇21和37与唾液酸供体22和38的区域选择性唾液酸化，在脱保护和内酰胺化后，分别得到SLe（x）-1“”->2-内酰胺1和SLe（x）-1“”-> 4 '-内酰胺4。三糖二醇21的亚锡烷基缩醛用溴乙酸叔丁酯区域选择性地3-O-烷基化;还原除去Tree保护基并加入甲醇MeONa导致形成内酰胺环。因此，经四个步骤以52%的总产率获得化合物40。脱保护40得到Le（x）-3，2-内酰胺6，产率74%。乳糖-二胺衍生物46与供体18的岩藻糖基化得到N-3-Le（x）三糖衍生物47。47的叠氮基官能团被H2S还原，这导致内酰胺环的自发闭合。然后除去保护基，得到Le（x）-3，4-内酰胺7。从单糖起始材料14、15、18、22、30、38和44得到1、2、3、4、5和7的总产率分别为10%、10%、22%、14%、62%和28%。
Virtually complete regioselective galactosylation of the diol acceptor p-methoxyphenyl 6-O-benzyl-2-deoxy-2-tetrachlorophthalimido-beta-D-glucopyranoside (15) with the donors ethyl 3,4-di-O-acetyl-6-O-benzyl-2-deoxy-2-[[(2,2,2-trichloroethoxy)carbonyl]amino]-1-beta-D-galactopyranoside (14), 4-methylphenyl 2,3-di-O-acetyl-4-azido-6-O-benzyl-4-deoxy-1-thio-beta-D-galactopyranoside (30), and 4-methylphenyl 2-O-acetyl-4-azido-6-O-benzyl-4-deoxy-3-O-(methoxyethanoyl)-1-thio-beta-D-galactopyranoside (44) gave the lactose-diamine derivatives 16, 33, and 45, respectively. Fucosylation of the NHAc derivatives of 16 and 33 (17 and 34) with the donor 18 gave, after deprotection and N-acetylation, the 2-NHAc-Le(x) and 4-NKAc-Le(x) trisaccharides 3 and 5, respectively. Removal of the Troc group from the tetrasaccharide intermediate 23, followed by N-acetylation (-->24), gave the NHAc-SLe(x) tetrasaccharide 2. Regioselective sialylation of the partially protected trisaccharide diols 21 and 37 with the sialyl donors 22 and 38 gave, after deprotection and lactamization, the SLe(x)-1'''-->2-lactam 1 and the SLe(x)-1'''-->4'-lactam 4, respectively. The stannylidene acetal of the trisaccharide diol 21 was regioselectively 3-O-alkylated with tert-butyl bromoacetate; reductive removal of the Tree protecting group and addition of methanolic MeONa caused formation of a lactam ring. Compound 40 was thus obtained over four steps in an overall yield of 52%. Deprotection of 40 furnished the Le(x)-3,2-lactam 6 in 74% yield. Fucosylation of the lactose-diamine derivative 46 with donor 18 gave the N-3-Le(x) trisaccharide derivative 47. The azido function of 47 was reduced with H2S, which caused spontaneous closure of a lactam ring. Removal of the protecting groups then gave the Le(x)-3,4-lactam 7. The total yields of 1, 2, 3, 4, 5, and 7 from the monosaccharide starting materials 14, 15, 18, 22, 30, 38, and 44 were 10%, 10%, 22%, 14%, 62%, and 28%, respectively.