Strategic Molecular Activations for the Selective Synthesis of 2-Deoxy-Beta-Glycosides, and for the Synthesis of Novel Donor-Acceptor Stenhouse Adducts

项目摘要/摘要 这项建议描述了利用基本化学性质来改变试剂的反应性 生物医学上重要化合物的合成。碳水化合物在生物系统中的作用不能 言过其实，对科学研究有很大的意义。健壮、实用、通用的糖基化方法 具有可预测立体选择性的反应将使进一步研究糖在生物化学中的作用成为可能 还有医学。尽管最近取得了进展，但多糖合成仍然是一项具有挑战性的工作，主要是为了 糖化学方面的专家，以及2-脱氧-β-糖苷的一般选择性合成仍然难以捉摸。 氢键供体催化剂将用于改变2-脱氧-a-磷酸供体的固有反应性 2-脱氧-β-糖苷(K99)的选择性合成。合成依赖于原位生成的磷酸盐 酯糖基供体，并对一种特制的有机催化剂进行鉴定，以促进立体特异性 通过同时激活亲电体(供体)和亲核体(受体)而发生的糖基化。 开发合成2-脱氧-β-糖苷的通用方法1)为 缺乏C2官能团的糖的糖基化，通常通过锚定辅助用作导向基团，2) 能够进一步研究它们在生物化学和医学中的作用，3)提供了一种替代方案 生物活性天然产物的合成策略。 其次，C-S键的化学性质将用于合成新型的给体-受体化合物 斯滕豪斯加合物，DASA(R00)。虽然斯滕豪斯加合物是在2014年推出的，但它们被用于药物 传输、动态相转移、聚合物、液晶、波长选择光开关和 化学传感应用。尽管DASA的应用前景看好，但目前受到其结构的限制 多样性。目前，在DASA系统中通常只使用胺供体和两个受体。新型加成物，含 硫、膦、氧或其他杂原子供体将扩大应用范围，并提供更多 已知应用的高效化合物。该合成依赖于使用2-噻吩甲醛，以及 经济的起始材料，将绕过使用呋喃甲醛时面临的反应性问题。2- 硫代苯甲醛含有更弱和更长的C-S键，而不是负责 在使用呋喃甲醛时不能在DASA中加入其他给体官能团；噻吩衍生物也携带 碳原子上的电子密度更低，使其成为冷凝后开环的理想衬底 受体分子。如果C-S键不够弱，则可极化的硫将用亲硫化合物活化 刘易斯酸。合成新的Stenhouse加合物1)提供更多的DASA来探索所列的应用 如上所述，2)能够进一步研究这些新型光开关的化学性质，以及3)提供 开发其他应用程序的机会。

Project Summary/Abstract This proposal describes the use of fundamental chemical properties to alter the reactivity of reagents for the synthesis of biomedically important compounds. The role of carbohydrates in biological systems cannot be overstated and is of great interest to scientific research. Robust, practical, and general methods for glycosylation reactions with predictable stereoselectivity will enable further research in the role of sugars in biological chemistry and medicine. Despite recent advances, glycan synthesis remains a challenging endeavor largely reserved for specialists in sugar chemistry, and a general, selective synthesis of 2-deoxy-β-glycosides remains elusive. Hydrogen-bond-donor catalysts will be used to alter the innate reactivity of 2-deoxy-a-phosphate donors for the selective synthesis of 2-deoxy-β-glycosides (K99). The synthesis relies on the in situ generation of a phosphate ester glycosyl donor, and on the identification of a tailored organocatalyst to promote stereospecific glycosylations by simultaneously activating the electrophile (the donor) and the nucleophile (the acceptor). Developing a general method for the synthesis of 2-deoxy-β-glycosides 1) provides a solution for the glycosylation of sugars lacking the C2 functionality often used as a directing group via anchimeric assistance, 2) enables further research on their role in biological chemistry and medicine, and 3) provides an alternative strategy for the synthesis of biologically active natural products. Secondly, the chemical properties of C–S bonds will be used for the synthesis of novel donor-acceptor Stenhouse adducts, DASAs (R00). Though Stenhouse adducts were introduced in 2014, they are used in drug delivery, dynamic phase transfer, polymers, liquid crystals, wavelength-selective photoswitching, and chemosensing applications. Despite their promising applications, DASAs are currently limited by their structural diversity. Only amine donors and two acceptors are generally used in DASA systems today. Novel adducts with sulfur, phosphine, oxygen, or other heteroatom donors will expand the pool of applications and provide more efficient compounds for known applications. The synthesis relies on using 2-thiophenecarboxaldehyde, an economical starting material that will circumvent reactivity problems faced when using furfural. 2- Thiophenecarboxaldehyde bears a weaker and longer C–S bond in place of the C–O bond responsible for the inability to incorporate other donor functionality in DASAs when using furfural; thiophene derivatives also carry less electron density on the carbon atoms, making it a perfect substrate for ring opening upon condensing an acceptor molecule. If the C–S bond is not sufficiently weak, the polarizable sulfur will be activated using thiophilic Lewis acids. Synthesizing novel Stenhouse adducts 1) provides additional DASAs to explore applications listed above, 2) enables further research on the chemical properties of these new photoswitches, and 3) provides an opportunity to develop additional applications.