New methods & strategies for oligosaccharide synthesis

描述(由申请人提供)：拟议研究的科学价值在于对基础和应用合成碳水化合物化学的贡献，这将导致项目成功完成。糖基硫代亚胺因其独特的反应性、立体选择性、易于制备和稳定性而成为潜在的有价值的合成构件。对这些糖基供体的探索将有助于更好地了解激活和离开基团的机制。由于其显著的立体选择性和反应性相对于稳定性，硫代亚胺化合物有可能在现代糖基化技术的武器库中找到一个重要的利基市场。随着硫代亚胺方法的发展，重点将转移到碳水化合物化学中武装和解除武装效果的研究以及反向武装-解除武装方法的发明上。对这些重要方面的研究只有由于糖基硫代亚胺的不同寻常的反应性和活化谱才有可能。开发这些技术将有助于展示硫代亚胺方法的合成潜力，同时还将提供参与癌症重要生物学过程的天然糖结合物的合成类似物。这项工作的其他重要方面涉及制备有机和碳水化合物化学方面的专业培训，以及本科生和研究生研究参与者将接受的复杂有机分子分析的现代物理化学方法。在这项提案中，2个暑期研究本科生奖学金和2个研究生职位被编入预算；PI的小组传统上支持妇女、儿童和少数族裔的参与。拟议研究的多学科性质将使学生能够在智力和实践意义上扩大他们的科学基础。在他们的实验室经验中，他们将学习重要的工具，使化学家能够合成、修饰和分析有机分子，同时开发新的(他们自己的)合成方法，并参与最先进的多步骤合成的精加工。学生研究人员还将通过参与编写同行评议的手稿和参加专业会议，充分融入科学界。通过这种方式，学生将发展更好的沟通技能，同时也接触到他们关注的研究领域以外的科学话语。

DESCRIPTION (provided by applicant): The scientific value of the proposed research lies in the contributions to basic and applied synthetic carbohydrate chemistry that will result upon successful completion of the project. Glycosyl thioimidates are potentially valuable synthetic building blocks due to their unusual reactivity profile, stereoselectivity, ease of preparation, and stability. Exploration of these glycosyl donors will provide better understanding of the mechanism of activation and the departure of the leaving group. Due to their remarkable stereoselectivity and reactivity vs. stability, the thioimidates have a potential to find an important niche in the arsenal of modern glycosylation techniques. Upon development of the thioimidate method, the focus will shift to the investigation of arming and disarming effects in carbohydrate chemistry and invention of the inverse armed-disarmed approach. Investigation of these important aspects will only be possible due to the unusual reactivity and activation profile of glycosyl thioimidates. Developing these techniques will serve to demonstrate the synthetic potential of thioimidate method while also delivering synthetic analogs of natural glycoconjugates that mediate important biological processes in carcinomas. Other important aspects of this work relate to the professional training in preparative organic and carbohydrate chemistry, as well as modern physico-chemical methods for analysis of complex organic molecules that the undergraduate and graduate research participants will receive. 2 summer research undergraduate fellowships and 2 graduate student positions are budgeted in this proposal; the PI's group has traditionally supported the involvement of women, children, and minorities. The multidisciplinary nature of the proposed research will allow students to expand their scientific base in both an intellectual and a practical sense. During their laboratory experience they will learn important tools that allow chemists to synthesize, modify, and analyze organic molecules while developing new ('their own') synthetic methodologies and participating in elaboration of state-of-the-art, multi-step syntheses. Student researchers will also become fully integrated into the scientific community through participation in the preparation of peer-reviewed manuscripts and through attendance at professional meetings. In this manner, students will develop better communication skills, while also being exposed to scientific discourse outside their focused area of research.