Glycosyl Cross-Coupling of Anomeric Nucleophiles: Scope, Mechanism, and Applications in the Synthesis of Aryl C-Glycosides.
Glycosyl Cross-Coupling of Anomeric Nucleophiles: Scope, Mechanism, and Applications in the Synthesis of Aryl C-Glycosides.
复制标题
DOI：
10.1021/jacs.7b08707
复制
发表时间：
2017-12-13
影响因子：
15
通讯作者：
Walczak MA
中科院分区：
文献类型：
--
作者：
Zhu F;Rodriguez J;Yang T;Kevlishvili I;Miller E;Yi D;O'Neill S;Rourke MJ;Liu P;Walczak MA
糖的C1位的立体选择性操作是制备碳水化合物化学的中心目标之一。从历史上看，大多数与异规碳形成键的反应都集中在亲核试剂与带有离开基团的糖给体的反应上。在这里，我们描述了一种新的方法来立体选择性地合成C-芳基糖苷，利用了异构体亲核试剂的高度立体特异性反应。首先，开发和优化了制备异构体锡烷的方法，以提供具有高异构体选择性的两种常见糖的异构体。我们发现，单糖锡烷可以通过与施密特型供体、糖环氧化物的O-糖基化反应或在脱水条件下与C1醇反应制备低聚糖锡烷。其次，我们确定了以Pd2(Dba)3(2.5mol%)和大分子配体(JackiePhos，10mol%)控制β消除途径的一般催化条件。我们证明，糖基交叉偶联导致具有单糖和寡糖、脱氧糖、带有游离羟基的糖、吡喃糖和呋喃糖底物的异构体具有一致的高选择性。探讨了糖基交叉偶联反应在Salmochelin(铁载体)和商业抗糖尿病药物(Gliflzins)的全合成中的多功能性。实验和计算相结合的研究表明，由于空间要求高的JackiePhos对Pd(II)的屏蔽，联苯型配体的β消除途径被抑制，而较小的配体，允许形成Pd−F络合物，主要导致糖基化产物。类似的空间效应解释了1，2-顺式氯-锡烷与芳基卤化物的交叉偶联速率降低的原因。密度泛函理论计算还表明，转金属化是通过保持非规位构型的循环过渡态进行的。总而言之，糖基交叉偶联反应易于获得各种糖苷类亲核试剂的两个异构体，反应范围广，异构体构型均一高转移，使糖基交叉偶联反应成为合成具有生物活性的天然产物、候选药物的实用工具，使小分子和生物制品的后期糖多样化研究成为可能。
Stereoselective manipulations at the C1 anomeric position of saccharides are one of the central goals of preparative carbohydrate chemistry. Historically, the majority of reactions forming a bond with anomeric carbon has focused on reactions of nucleophiles with saccharide donors equipped with a leaving group. Here, we describe a novel approach to stereoselective synthesis of C-aryl glycosides capitalizing on the highly stereospecific reaction of anomeric nucleophiles. First, methods for the preparation of anomeric stannanes have been developed and optimized to afford both anomers of common saccharides in high anomeric selectivities. We established that oligosaccharide stannanes could be prepared from monosaccharide stannanes via O-glycosylation with Schmidt-type donors, glycal epoxides, or under dehydrative conditions with C1 alcohols. Second, we identified a general set of catalytic conditions with Pd2(dba)3 (2.5 mol%) and a bulky ligand (JackiePhos, 10 mol%) controlling the β-elimination pathway. We demonstrated that the glycosyl cross-coupling resulted in consistently high anomeric selectivities for both anomers with mono-and oligosaccharides, deoxysugars, saccharides with free hydroxyl groups, pyranose, and furanose substrates. The versatility of the glycosyl cross-coupling reaction was probed in the total synthesis of salmochelins (siderophores) and commercial anti-diabetic drugs (gliflozins). Combined experimental and computational studies revealed that the β-elimination pathway is suppressed for biphenyl-type ligands due to the shielding of Pd(II) by sterically demanding JackiePhos, whereas smaller ligands, which allow for the formation of a Pd−F complex, predominantly result in a glycal product. Similar steric effects account for the diminished rates of cross-couplings of 1,2-cis C1-stannanes with aryl halides. DFT calculations also revealed that the transmetalation occurs via a cyclic transition state with retention of configuration at the anomeric position. Taken together, facile access to both anomers of various glycoside nucleophiles, a broad reaction scope, and uniformly high transfer of anomeric configuration make the glycosyl cross-coupling reaction a practical tool for the synthesis of bioactive natural products, drug candidates, allowing for late-stage glycodiversification studies with small molecules and biologics.
登录
查看更多内容
影响因子：
1.8
作者：
Chamoin, S;Houldsworth, S;Snieckus, V
通讯作者：
Snieckus, V
影响因子：
15
作者：
Aranyos, A;Old, DW;Buchwald, SL
通讯作者：
Buchwald, SL
影响因子：
2.1
作者：
Baek, Ju Yuel;Kwon, Hea-Won;Kim, Kwan Soo
通讯作者：
Kim, Kwan Soo
影响因子：
2.8
作者：
Ariafard, Alireza;Lin, Zhenyang;Fairlamb, Ian J. S.
通讯作者：
Fairlamb, Ian J. S.
影响因子：
16.6
作者：
Andrews, R. Stephen;Becker, Jennifer J.;Gagne, Michel R.
通讯作者：
Gagne, Michel R.