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>> Total Synthesis of Echinoside A, a Representative Triterpene Glycoside of Sea Cucumbers
>> Synthesis of Bradyrhizose Oligosaccharides Relevant to the Bradyrhizobium O-Antigen / Synthesis of bradyrhizose, a unique inositol-fused monosaccharide relevant to a Nod-factor independent nitrogen fixation
>> Gold(I)-catalyzed C-glycosylation of glycosyl ortho-alkynylbenzoates: the role of the moisture sequestered by molecular sieves
>> Total Synthesis of Linckosides A and B, the Representative Starfish Polyhydroxysteroid Glycosides with Neuritogenic Activities
>> Highly Stereoselective β-Mannopyranosylation via the 1-α-Glycosyloxy-isochromenylium-4-gold(I) Intermediates / Stereoselective synthesis of β-rhamnopyranosides via gold(i)-catalyzed glycosylation with 2-alkynyl-4-nitro-benzoate donors
>> A Modular Approach to the Total Synthesis of Tunicamycins
>> Total synthesis of periploside A, a unique pregnane hexasaccharide with potent immunosuppressive effects
>> 抗生素A201A的首次全合成
>> Mechanistic insights into the gold(I)-catalyzed activation of glycosyl ortho-alkynylbenzoates for glycosidation
>> 开发出人参皂苷的合成方法 Synthesis of Ginsenosides
>> 本课题组有关天然糖苷的合成小结: 由此发展的合成策略和糖苷化方法
>> 具有显著抗肿瘤活性的angucycline类抗生素Landomycin A的首次全合成 / 对于Landomycin A的全合成研究历经15年有余，其历程总结于此文
>> 一价金催化的糖基邻炔基苯甲酸酯的糖苷化反应: 关键金中间体的表征
>> 一价金催化的糖基邻炔基苯甲酸酯的糖苷化反应的应用: 核苷的高效合成
>> 首次发现糖苷化引发的四氢呋喃的正离子开环聚合反应: 新颖糖基聚醚的制备
>> 乙酰氨基葡萄糖苷水解酶的首个选择性抑制剂TMG-chitotriomycin的合成和结构修正 / TMG-chitotriomycin的构效关系
>> 具有抗增殖活性的海洋甾体化合物Hippuristanol及类似物的首次合成 / Hippuristanol的进一步构效关系
>> 具有显著抗肿瘤活性的环状三萜皂苷Lobatoside E的全合成
>> 关于三萜皂苷的合成进展
>> 一个代表性的断环三萜皂苷Betavulgaroside III的全合成
>> 具有显著抗肿瘤活性的带有重排边链的甾体皂苷Candicanoside A的全合成
>> 皂苷的细胞毒性与其在细胞内的内吞定位相关
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Total Synthesis of Echinoside A, a Representative Triterpene Glycoside of Sea CucumbersXiaoping Chen, Xiaofei Shao, Wei Li, Xiaheng Zhang & Biao Yu*Angew. Chem. Int. Ed. 2017, 56, 7648-7652. Echinoside A, a sulfonylated holostane tetrasaccharide
with potent anticancer and antifungal activity, was
synthesized in a longest linear sequence of 35 steps and 0.6%
overall yield. The synthetic approach is adaptable to the
synthesis of congeners and analogues, as exemplified by the
ready synthesis of ds-echinoside A and echinoside B, and thus
will facilitate in-depth studies on the promising biological
effects of echinoside A. Moreover, the present synthesis
demonstrates the feasibility of synthetic access to the characteristic
complex triterpene glycosides that occur ubiquitously in
sea cucumbers.
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Synthesis of Bradyrhizose Oligosaccharides Relevant to the Bradyrhizobium O-Antigen.Wei Li, Alba Silipo, Lotte Bettina Andersen Gersby, Mari-Anne Newman, Alba Silipo, Antonio Molinaro* & Biao Yu*Angew. Chem. Int. Ed. 2017, 56, 2092-2096. The unique α-(1→7)-bradyrhizoside linkages are constructed for the first time via judicious choice of the glycosylation partners and conditions, thus tetra- and penta-bradyrhizosides relevant to the peculiar O-antigen of Bradyrhizobium are synthesized, which are shown to adopt the defined right-handed helical conformations and to be unable to induce innate immune responses in plants.
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Synthesis of bradyrhizose, a unique inositol-fused monosaccharide relevant to a Nod-factor independent nitrogen fixation.Wei Li, Alba Silipo, Antonio Molinaro* & Biao Yu*Chem. Commun. 2015, 51, 6964-6967. The symbiosis of Bradyrhizobium sp. BTAi1 with its host plant Aeschynomene indica relies on a Nod-factor independent mechanism, wherein the Bradyrhizobium O-antigen is regarded as a key factor. This O-antigen polysaccharide is composed of a unique C10 monosaccharide, namely bradyrhizose, which has a galactose–inositol trans-fused scaffold, via a homogeneous α-(1 → 7)-linkage. Herein, we report the first synthesis of bradyrhizose. The scalable synthesis requires 26 steps in a high overall yield of 9%, with the inositol scaffold being constructed effectively via a Ferrier II rearrangement from a fully functionalized C2 and C4 branched pyranose derivative.
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Gold(I)-catalyzed C-glycosylation of glycosyl ortho-alkynylbenzoates: the role of the moisture sequestered by molecular sievesXiaoping Chen, Qiaoling Wang & Biao Yu*Chem. Commun. 2016, 52, 12183-12186. C-Glycosylation of glycosyl ortho-hexynylbenzoates with allyltrimethylsilane
or silyl enol ethers could proceed smoothly under the
catalysis of Ph3PAuNTf2 to provide the corresponding C-glycosides
in high yields and stereoselectivity, wherein the moisture sequestered
by the molecular sieves was disclosed to play a critical role in the
gold(I)-catalytic cycle.
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Total Synthesis of Linckosides A and B, the Representative Starfish Polyhydroxysteroid Glycosides with Neuritogenic Activities.Dapeng Zhu & Biao Yu*J. Am. Chem. Soc. 2015, 137, 15098-15101. Linckosides A and B, two starfish metabolites with promising neuritogenic activities, are synthesized in a longest linear sequence of 32 steps and 0.5% overall yield; this represents the first synthesis of members of the polyhydroxysteroid glycoside family which occur widely in starfishes.
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Inside Cover: Highly Stereoselective β-Mannopyranosylation via the 1-α-Glycosyloxy-isochromenylium-4-gold(I) Intermediates.Yugen Zhu & Biao Yu*Chem. Eur. J. 2015, 21, 8771-87801. While the gold(I)-catalyzed glycosylation reaction with 4,6-O-benzylidene tethered mannosyl ortho-alkynylbenzoates as donors falls squarely into the category of the Crich-type β-selective mannosylation when Ph3PAuOTf is used as the catalyst, in that the mannosyl α-triflates are invoked, replacement of the ?OTf in the gold(I) complex with less nucleophilic counter anions (i.e., ?NTf2, ?SbF6, ?BF4, and ?BAr4F) leads to complete loss of β-selectivity with the mannosyl ortho-alkynylbenzoate β-donors. Nevertheless, with the α-donors, the mannosylation reactions under the catalysis of Ph3PAuBAr4F (BAr4F=tetrakis[3,5-bis(trifluoromethyl)phenyl] borate) are especially highly β-selective and accommodate a broad scope of substrates; these include glycosylation with mannosyl donors installed with a bulky TBS group at O3, donors bearing 4,6-di-O-benzoyl groups, and acceptors known as sterically unmatched or hindered. For the ortho-alkynylbenzoate β-donors, an anomerization and glycosylation sequence can also ensure the highly β-selective mannosylation. The 1-α-mannosyloxy-isochromenylium-4-gold(I) complex (Cα), readily generated upon activation of the α-mannosyl ortho-alkynylbenzoate (1?α) with Ph3PAuBAr4F at ?35?°C, was well characterized by NMR spectroscopy; the occurrence of this species accounts for the high β-selectivity in the present mannosylation.
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Stereoselective synthesis of β-rhamnopyranosides via gold(i)-catalyzed glycosylation with 2-alkynyl-4-nitro-benzoate donorsYugen Zhu,∇ Zhengnan Shen,∇ Wei Li & Biao Yu* (∇=同等贡献)Org. Biomol. Chem. 2016, 14, 1536-1539.Stereoselective β-rhamnopyranosylation remains a challenge, due to the unfavorable anomeric effect and steric hindrance of the C2- substituent; herein, this challenge is addressed with a gold(I)-catalyzed SN2-like glycosylation protocol employing α-rhamnopyranosyl 2-alkynyl-4-nitro-benzoates as donors. | |
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A Modular Approach to the Total Synthesis of Tunicamycins.Jiakun Li & Biao YuAngew. Chem. Int. Ed. 2015, 54, 6618-6621. The tunicamycins constitute a delicate mimic of the bisubstrate intermediates of N-acetyl-d-hexosamine-1-phosphate translocases and thus inhibit bacterial cell-wall synthesis and the N?glycosylation of eukaryotic proteins. An efficient approach to the synthesis of this unique type of nucleoside antibiotics is now reported and features the assembly of five modules in a highly stereoselective and robust manner. A Mukaiyama aldol reaction, intramolecular acetal formation, gold(I)-catalyzed O and N?glycosylation, and final N?acylation were used as the key steps.
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Total synthesis of periploside A, a unique pregnane hexasaccharide with potent immunosuppressive effects.Xiaheng Zhang, Yu Zhou, Jianping Zuo & Biao YuNat. Commun. 2015, 6, 5879. Periploside A is a pregnane hexasaccharide identified from the Chinese medicinal plant Periploca sepium, which features a unique seven-membered formyl acetal bridged orthoester (FABO) motif and potent immunosuppressive activities. Here, we show the synthesis of this molecule in a total of 76 steps with the longest linear sequence of 29 steps and 9.2% overall yield. The FABO motif is constructed via a combination of Sina?’s and Crich’s protocol for the formation of orthoester and acetal glycosides, respectively. The 2-deoxy-β-glycosidic linkages are assembled stereoselectively with judicious choice of the glycosylation methods. The epimer at the spiro-quaternary carbon in the FABO motif has also been elaborated in a stereo-controlled manner. This epimer, as well as the synthetic analogues bearing the FABO motif, retain largely the inhibitory activities of periploside A against the proliferation of T-lymphocyte, indicating the importance of the chemical connection of the FABO motif to their immunosuppressive activity.
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Total synthesis of nucleoside antibiotic A201A.Shenyou Nie, Wei Li, Biao Yu.*J. Am. Chem. Soc. 2014, 136, 4157-4160. A201A是一个结构独特的核苷类抗生素，其中含环外烯醚的呋喃糖单元从未在其它天然产物中出现过。该抗生素由美国礼来公司于1976年从链霉菌Streptomyces capreolus NRRL 3817中分离得到，对革兰氏阳性菌和大多数厌氧性革兰氏阴性菌显示出强烈的抗菌活性。由于该化合物含有模拟tRNA末端的3’－酰胺基核苷片段，推测其作用于核糖体A位从而抑制蛋白质的合成。2012年，中科院南海海洋研究所鞠建华课题组从南中国海海底获取的放线菌株Actinomycetes thermotolerans中又意外地分离得到A201A，并对其独特的生物合成途径开展了研究。
聂神有同学近期完成了对A201A的首次全合成。该合成采用了线性的合成策略，通过对5个砌块的糖苷化和酰胺化完成拼接。其中通过Mitsunobu糖苷化高立体选择性地实现了呋喃糖1,2-顺式糖苷键的构建；通过优化条件立体选择性地实现了E式烯醇甲醚的合成；通过该课题组发展的一价金促进的糖苷化反应实现了嘌呤的N－糖苷化；并实现了对含有酸性敏感基团和碱性氮原子的复杂底物的糖苷化。这种线性和模块化的合成策略也为A201A类似物的发散性合成以进行构效关系的研究提供了可能。
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Synthetic Access Toward the Diverse GinsenosidesY. Tang (唐宇),∇ J. Li (李家昆),∇ Y. Zhu (朱玉根), Y. Li (李瑶), B. Yu* (∇=同等贡献)J. Am. Chem. Soc. 2013, 135, 18396-18405.Anomerization, which involves cleavage and formation of the anomeric C-O bond, is of fundamental importance in the carbohydrate chemistry. Herein, the unexpected gold(I)-catalyzed anomerization of glycosyl ortho-alkynylbenzoates has been studied in details. Especially, crossover experiments in the presence of an exogenous isochromen-4-yl gold(I) complex confirm that the anomerization proceeds via the exo-cleavage mechanism, involving (surprisingly) the addition of the isochromen-4-yl gold(I) complex onto a sugar oxocarbenium and an elimination of LAu+ from the vinyl gold(I) complex. The inhibitory effect of the exogenous isochromen-4-yl gold(I) complex when in stoichiometric amount on the anomerization has guided us to disclose an isochromen-4-yl gem-gold(I) complex, which is inactive in catalysis but in equilibrium with the mono-gold(I) complex and the LAu+ catalyst. The proposed key intermediate in the anomerization, a transient glycosyloxypyrylium species, is successfully trapped via a cycloaddition reaction with n-butyl vinyl ether as a dienophile. SN2-like substitution of the initially formed glycosyloxypyrylium intermediate has then been achieved to a large extent via charging with acceptors in an excess amount to lead to the corresponding glycosides in a highly stereoselective manner. 
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Synthetic Access Toward the Diverse GinsenosidesJun Yu, Jiansong Sun,* Yiming Niu, Rongyao Li, Jinxi Liao, Fuyi Zhang, Biao Yu,*Chem. Sci. 2013, 4, 3899–3905. 人参是最著名和最常用的中药。一些研究表明人参的诸多神奇功效与其所含的人参皂苷有关。人参皂苷主要是以（达玛烷型三萜）原人参二醇和三醇为苷元的糖苷化合物。到目前为止已经从人参类植物中分离鉴定的人参皂苷多达200多个；从这样的复杂混合物中通过分离手段获取足量的单一人参皂苷极其困难。因此，限制了在分子水平上对人参皂苷的活性研究和药物开发。 | |
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Assembly of Naturally Occurring Glycosides, Evolved Tactics and Glycosylation MethodsB. Yu,* J. Sun (孙建松), X. Yang (杨晓瑜)Acc. Chem. Res. 2012, 45, 1227-1236.Post-modification of proteins and lipids by glycosylation is critically important to many life processes. The secondary metabolites (or natural products), such as flavonoids, steroids, triterpenes, and antibiotics, are also frequently post-modified with saccharides. These ubiquitous glycosides are extremely diverse in structures and functions, and some of them are of pharmacological significance. The saccharide parts of the glycosides are structurally characteristic depending on the aglycones and are often in heterogeneous ‘glycoform’ with similar linkage but varied length and monosaccharide units. Thus, purification of a homogeneous glycoside from the nature sources, especially in an appreciable amount, is always difficult. Chemical synthesis provides a feasible access to the homogenous glycosides and their congeners. However, synthetic efforts are dedicated usually to the aglycones, and the attachment of saccharides onto the aglycones is treated as a dispensable topic. Synthesis of a glycoside involves the synthesis of the aglycone, the saccharide, the connection of these two parts, and the overall manipulation of protecting groups. The synthesis of the aglycone and the synthesis of the saccharide belong to two independent categories of chemistry. Moreover, different types of the aglycones and saccharides pose as specific synthetic subjects in their own discipline. The only reaction which integrates the broad chemistry of glycoside synthesis is the glycosidic bond formation between the saccharide and the aglycone, although this linkage is also very diverse in nature. Focusing on this glycosylation reaction, we string together in this Account our own experience with the synthesis of the naturally occurring glycosides. The syntheses of eighteen glycosides, including glycolipids, phenolic glycosides, steroid glycosides, and triterpene glycosides, each represents a prototypical structure of a big or small family of the natural glycosides with interesting biological activities, are briefly described. Emphasis is then placed on the general tactical consideration of the synthesis of these diverse structures. Basing on the stage at which the glycosidic bond between the saccharide and the aglycone is constructed, four tactics to secure the synthesis of glycosides are rationalized, which also determine the flexibility and the overall efficiency of the synthesis. Toward the synthesis of the ‘glycoform’ of glycosides, successive glycosylation and random glycosylation are discussed. Finally, the challenges have been addressed for the glycosylation of aglycones which are poorly nucleophilic or extremely labile to acid or electrophile by the development of two new glycosylation protocols, i.e, the glycosylation with glycosyl trifluoroacetimidates as donors and the gold(I)-catalyzed glycosylation with glycosyl ortho-alkynylbenzoates as donors. 
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Total synthesis of Landomycin A, a potent antitumor angucycline antibioticsX. Yang (杨晓瑜), B. Fu (付伯桥), B. Yu*J. Am. Chem. Soc. 2011, 133, 12433-12435.The first total synthesis of Landomycin A, the longest and the most potent antitumor angucycline antibiotics, has been achieved in overall 63 step and 0.34% yield starting from 2,5-dihydroxybenzoic acid, 3,5-dimethylphenol, triacetyl D-glucal, and D-xylose, with a convergent linear sequence of 21 steps. 
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Tackle the challenges in the total synthesis of landomycin AX. Yang (杨晓瑜), P. Wang (王平), B. Yu*Chem. Rec. 2013, 13, 70–84.The twists and turns toward the total synthesis of landomycin A, a prominent angucycline hexasaccharide antibiotics, especially those toward stereoselective construction of the di- and trideoxyglycosidic linkages, are accounted. | |
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Characterization of the isochromen-4-yl-gold(I) intermediate in the gold(I)-catalyzed glycosidation of glycosyl o-alkynylbenzoates and enhancement of the catalytic efficiency thereofY. Zhu (朱玉根), B. Yu*Angew. Chem. Int. Ed. 2011, 50, 8329-8331.We have characterized unambiguously the isochromen-4-yl-gold(I) complex (i.e., D) as an important intermediate in the gold(I)-catalyzed glycosylation reaction with glycosyl o-alkynylbenzoates as donors. Effective protodeauration of this vinyl gold(I) complex has shown to require strong protic acid, and this is found to be critical for regeneration of the active gold(I) species for the catalytic cycle. 
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An efficient approach to the synthesis of nucleosides, gold(I)-catalyzed N-glycosylation of pyrimidines and purines with glycosyl ortho-alkynylbenzoatesQ. Zhang (张庆举), J. Sun (孙建松),* Y. Zhu (朱玉根), F. Zhang (张福义), B. Yu,*Angew. Chem. Int. Ed. 2011, 50, 4933-4935.The easily accessible and shelf-stable glycosyl ortho-hexynylbenzoates have been proven to be superior donors for N-glycosylation of nucleobases under the catalysis of Ph3PAuNTf2. The present success of highly efficient and regioselective N9-glycosylation of purines attributes to the mild glycosylation conditions that allow Boc-protected purine derivatives to be used as the coupling partners for the first time. 
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Glycosylation initiated cationic ring-opening polymerization of tetrahydrofuran to prepare neo-glycopolymersY. Li (李瑶), B. Yu*Chem. Commun. 2010, 46, 6060-6062.An unprecedented and highly efficient glycosylation initiated cationic ring-opening polymerization (CROP) of tetrahydrofuran has been disclosed employing glycosyl ortho-hexynylbenzoates as donors and gold(I) as a catalyst, that provides an easy access to novel glycopolymers which could self-assemble into nanostructures. 
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Total Synthesis and Structural Revision of TMG-chitotriomycin, a Specific Inhibitor of Insect and Fungal Beta-N-AcetylglucosaminidasesY. Yang (杨友), Y. Li (李瑶), B. Yu*J. Am. Chem. Soc. 2009, 131, 12076-12077.TMG-chitotriomycin, a potent and selective inhibitor of the Beta-N-acetylglucosaminidases which possesses an unique N,N,N-tri-methyl-D-glucosamine (TMG) residue, is revised to be the TMG-Beta-(1->4)-chitotriose instead of the originally proposed alpha-anomer via total synthesis, where a highly convergent approach is developed with the sterically demanding (1->4)-glycosidic linkages being efficiently constructed by the Au(I)-catalyzed glycosylation protocol with glycosyl o-hexynylbenzoates as donors. 
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Synthesis, evaluation, and mechanism of N,N,N-trimethyl-D-glucosamine-(1->4)-chitooligosaccharides as selective inhibitors of glycosyl hydrolase family 20 Beta-N-acetyl-D-hexosaminidasesY. Yang (杨友), T. Liu (刘田), Y. Yang, Q. Wu, Q. Yang (杨青),* B. Yu,*ChemBioChem 2011, 12, 457-467. | |
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Expeditious synthesis of Hippuristanol and congeners with potent antiproliferative activitiesW. Li (李微), Y. Dang (党永军), J. O. Liu (刘钧),* B. Yu*Chem. Eur. J. 2009, 15, 10356-10359.Hippuristanol and its congeners comprise a family of structurally unique polyoxygenated steroids isolated from the gorgonian Isis hippuris, which inhibit eukaryotic translation initiation and tumor cell proliferation effectively. An expeditious synthesis of hippuristanol was developed that allowed for rapid access to a number of analogs with structural alteration at its E and F rings, facilitating the structure/activity relationship studies of the novel inhibitor of eukaryotic translation initiation. 
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Structural and stereochemical requirements of the spiroketal group of hippuristanol for antiproliferative activityW. Li, Y. Dang, J. O. Liu,* B. Yu,*Bioorg. Med. Chem. Lett. 2010, 20, 3112-3115. | |
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Total synthesis of Lobatoside E, a potent antitumor cyclic triterpene saponinC. Zhu (祝存生), P. Tang (汤平平), B. Yu,*J. Am. Chem. Soc. 2008, 130, 5872-5873.Lobatoside E, a novel and complex cyclic triterpene saponin showing potent antitumor activities, has been synthesized for the first time, employing a highly modular approach. The synthesis, starting with oleanolic acid, D-glucose, D-galactose, L-arabinose, and L-rhamnose, requires a total of 73 steps, with the longest linear sequence of 31 steps and in 1.2% overall yield. 
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Current synthesis of triterpene saponinsB. Yu,* J. Sun (孙建松)Chem. Asian J. 2009, 4, 642-654. | |
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Synthesis of Betavulgaroside III, a representative triterpene seco-glycosideS. Zhu (朱石磊), Y. Li (李英霞), B. Yu*J. Org. Chem. 2008, 73, 4978-4985.Triterpene seco-glycosides constitute a small family of the plant saponins, which feature a terminal seco-saccharide appendage deriving supposedly from oxidative scission of a monosaccharide unit. We have developed synthetic approaches for the first time to the access to these molecules. Betavulgaroside III, a representative congener occurring in Beta vulgaris and Achyranthes fauriei, is successfully synthesized in a total of 31 steps with L-arabinose, D-glucose, and oleanolic acid as starting materials. The longest linear sequence requires 23 steps and in an overall 0.9% yield. 
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Total synthesis of Candicanoside A, a potent antitumor saponin bearing a rearranged steroid side chainP. Tang (汤平平), B. Yu,*Angew. Chem. Int. Ed. 2007, 46, 2527-2530.Candicanoside A, a novel saponin showing potent antitumor activities in a unique differential pattern, has been synthesized, in a linear sequence of 27 steps and 1.0% overall yield, for the first time. 
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The cytotoxicity of saponins correlates with their cellular internalizationY. Wang (王一兵), Y. Zhang (张一纯), B. Yu*ChemMedChem 2007, 2, 888-291 (Cover Story)The picture shows three structurally similar steroid glycosides bearing fluorescent tags. One crosses the cell membrane faster (top, straight arrow) than the other (left, curved path) to localize in lysosome (red sphere). The third (middle), with a cholesterol aglycone moiety, does not enter into the cell at all. Steroid glycosides are abundant natural surfactants known as saponins, which have membrane-disrupting properties. However, the three saponins represented here are not found in the cell membrane, where cholesterol and sugar chains are abundant. 
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