信息摘要：
2026年，中国科学院新疆理化技术研究所与上海药物研究所等团队合作在《The Journal of Organic Chemistry》发表研究论文《Photo-Induced Stereoselective Synthesis of C-Glycosides via Conformation-Locked Glycosyl Radical Coupling》(DOI: 10.1021/acs.joc.5c03266)，研究中使用LUYOR-3416 LED光反应器对糖苷自由基偶联反应体系进行465 nm蓝色LED辐照，实现了β-烷基C-糖苷的高立体选择性合成，为无光催化剂、无过渡金属的C-糖苷类药物骨架构建策略提供了关键实验证据。
中科院新疆理化技术研究所将LUYOR-3416用于β-C-糖苷立体选择性合成实验
C-糖苷是碳水化合物类药物研发的重要骨架，具有优良的药理学性质和代谢稳定性，已被成功应用于恩格列净(Empagliflozin)等SGLT2抑制剂类药物的设计。然而，在温和条件下实现特定异头物的立体选择性合成，尤其是β-异头物，仍是糖化学领域的重大挑战。2026年，中国科学院新疆理化技术研究所团队（联合中科院上海药物研究所）在《The Journal of Organic Chemistry》发表研究论文《Photo-Induced Stereoselective Synthesis of C-Glycosides via Conformation-Locked Glycosyl Radical Coupling》，报道了一种可见光介导、无光催化剂、无过渡金属的β-烷基C-糖苷立体选择性合成策略。LUYOR-3416 LED光反应器在该研究中作为核心光源设备，通过48 W蓝色LED（光谱范围460−470 nm，峰值波长约465 nm）持续辐照，驱动基于单电子转移(SET)的糖苷自由基偶联反应，确保反应在室温、氮气保护条件下高效、可重复地进行，LUYOR-3416 LED光反应器为反应结果的可重复性与可靠性提供保障。
该方法的要点在于利用大位阻叔丁基二甲基硅基(TBS)保护的2,3,5,6-四氟吡啶-4-硫基(SPyf)糖苷前体，诱导糖环发生从4C1椅式到1C4椅式的构象翻转，从而克服糖苷自由基中间体固有的立体化学倾向。在LUYOR-3416 LED光反应器的持续蓝光辐照下，缺电子的SPyf片段作为单电子氧化剂触发脱硫反应，经单电子转移(SET)产生碳中心糖苷自由基，随后被烯烃受体从β面立体选择性捕获，并经氢原子转移(HAT)生成β-C-糖苷产物。LUYOR-3416 LED光反应器采用平行LED光源底部辐照设计，可同时支持多组反应平行进行，光源波长可依实验需求选择更换、强度可调，可在真空、惰气保护等条件下用于光合成反应、光催化筛选等可见光化学研究，是高校和科研院所光化学反应实验的理想选择。
本实验采用LUYOR-3416 LED光反应器作为β-C-糖苷立体选择性合成实验的核心光源设备，用于为糖苷自由基偶联反应提供465 nm蓝色LED辐照。实验以TBS保护的SPyf木糖2a(0.1 mmol)与丙烯酸苄酯3f(0.15 mmol)为模型底物，加入Hantzsch酯(HE, 0.2 mmol)、NaOAc(0.25 mmol)与无水DMF(2 mL, 0.05 M)，经氮气置换三次后在LUYOR-3416 LED光反应器中以48 W蓝色LED持续辐照、室温搅拌15−18 h，以82%的收率得到β-烷基C-糖苷4f；对照实验证实HE、碱、蓝光辐照与惰性气氛均为必需条件，缺失任一组分均无法检测到产物。在底物拓展中，丙烯酸酯、丙烯酰胺、乙烯基苯基酮、二乙基乙烯基膦酸酯、丙烯腈与乙烯基砜等α,β-不饱和化合物与TBS保护的SPyf木糖2a发生立体选择性偶联，以21%−88%的收率得到相应β-烷基C-糖苷(4a−4m)；通过numbering-up策略进行的放大实验中，1.0 mmol反应分装于LUYOR-3416 LED光反应器的10支反应管平行辐照18 h，合并处理后以71%收率得到4f。此外，该方法成功应用于多肽衍生物及生物活性分子类似物的C-糖苷化，金刚烷胺衍生物3q与供体2a偶联得到β-C-糖苷4x，雌酮与鬼臼毒素的甲基丙烯酸酯衍生物分别以64%和75%的收率、优异的β选择性得到目标产物(4y, 4z)，充分展示了该方法在药物相关分子修饰中的应用潜力。
该研究证实，LUYOR-3416 LED光反应器可用于可见光介导的糖苷自由基偶联反应中反应体系的持续蓝光辐照，适用于β-C-糖苷立体选择性合成、光催化筛选等可见光化学研究场景，其稳定的光源输出为反应条件的一致性、结果的可重复性与可靠性提供保障。LUYOR-3416 LED光反应器在国内外高校和科研院所得到广泛好评，欢迎私信或留言上海路阳了解详情！
原文段落
光化学反应光源原文
The photochemical reaction was carried out under visible light irradiation by the LUYOR-3416 LED photoreactor, purchased from Shanghai LUYOR Biotech Co. Ltd. (Input: AC100−240 V, 50/60 Hz; Output: 48 W). The light source consists of blue LED beads, providing a spectral distribution of 460−470 nm, with a peak emission wavelength of approximately 465 nm. The reaction mixtures were irradiated in standard borosilicate glass Schlenk tubes, which were placed directly into the reactor's custom irradiation wells (distance<0.5 cm from the light source).
反应优化与底物范围原文
In accordance with the aforementioned findings, we selected TBS-protected SPyf xylose 2a and benzyl acrylate 3f as model substrates to optimize the reaction conditions. Under 465 nm irradiation (48 W blue LEDs) with K2CO3 as base, Hantzsch ester (HE) as hydrogen donor, and DMF as solvent, β-alkyl C-glycoside 4f was produced in 80% yield (Table 1, entry 1). … Notably, NaOAc achieved yields comparable to K2CO3 (82% vs 80%). Control experiments (entries 20−23) confirmed that HE, base, blue LEDs, and inert atmosphere were all prerequisites, as the omission of any component led to no detectable product formation. … Following the establishment of optimal conditions, we investigated the substrate scope (Scheme 3). Various α,β-unsaturated compounds such as acrylates, acrylamides, vinyl phenyl ketone, diethyl vinyl phosphonate, acrylonitrile, and vinyl sulfone underwent stereoselective coupling with TBS-protected SPyf xylose 2a, resulting in the corresponding β-alkyl C-glycosides in yields ranging from 21% to 88% (4a−4m). … Accordingly, a 1.0 mmol scale reaction was prepared and divided into ten vials, providing 4f in 71% yield.
研究结论原文
In conclusion, we have developed an efficient and photocatalyst-free method for the stereoselective synthesis of β-alkyl C-glycosides under mild visible-light irradiation. By using conformationally restricted SPyf thioglycoside donors, this method enables the precise installation of various alkyl groups at the anomeric position C1. Although the selectivity of stereochemistry is governed by a delicate interaction between the anomeric effect and steric hindrance, our results demonstrate that this strategy is particularly effective for the construction of β-configured C-xylosides. Furthermore, these findings offer significant mechanistic insights into the hexose series. The practical utility of this method was further demonstrated through the glycosylation of peptide derivatives and the analogs of bioactive compounds. Mechanistic investigations, including radical trapping and light on−off experiments, confirmed the participation of anomeric radical intermediates and the necessity for continuous blue-light irradiation. UV−vis absorption spectroscopy verified the formation of an EDA complex between TBS-protected SPyf D-xylose, Hantzsch ester, and NaOAc. Our findings highlight that the reaction efficiency is highly sensitive to the steric fit of the base and the solubility of the glycosyl donors.
DOI:doi.org/10.1021/acs.joc.5c03266
