光触媒による2－デオキシ糖の立体選択的グリコシル化の開発とミスラマイシンの全合成

2019 Fiscal Year Annual Research Report

• Project/Area Number: 19F01098
• Research Institution: Gifu University
• Principal Investigator: 安藤 弘宗 岐阜大学, 研究推進・社会連携機構, 教授 (20372518)
• Co-Investigator(Kenkyū-buntansha): VIBHUTE AMOL 岐阜大学, 研究推進・社会連携機構, 外国人特別研究員
• Project Period (FY): 2019-10-11 – 2022-03-31
• Keywords: glycosylation / visible light activation / glycal

Outline of Annual Research Achievements

We commenced our proposed project with the synthesis of building blocks required in this study. We have synthesized variety of diverse sugar derivatives such as tribenzyl glucal, triacetyl glucal/galactal as donors and 2,3,4-tri-O-benzyl α-methylglucoside as acceptor to test the hypothesis. Then we have carried out the initial screening of a photocatalyst such as fac-Ir(ppy)3 by using hexaphenyl disilane as silylating agent in presence of blue LED as light source. When the initial attempts were failed, we employed various reaction conditions to check the feasibility of this reaction. Unfortunately, we could not succeed to generate the silyl radical by this process. Then we turn our attention towards another photocatalyst. We have performed several reactions using Eosin Y as photocatalyst and different silylating reagents and light sources to carry out the coupling reaction. However, under this condition also the desired product could not formed.
In order to check whether the silylating reagent undergo radical formation or not, we employed known radical initiators such as AIBN and CAN. In the presence of both these radical initiators the tribenzyl glucal undergo glycosylation reaction, albeit without the incorporation of silyl functionality. To enhance the reactivity of the silylating reagent, we synthesized more reactive N-(trimethylsilyl)phthalimide. Under this condition also the desired conversion could not achieved so far. Our future plan will be to screen various combinations of these parameters and find the optimal condition to perform the glycosylation reaction.

Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

While proposing the project, we have set the milestones to be achieved along with the time span. We planned to commence our study with the synthesis of building blocks such as donors and acceptors. During this time we also planned to carry out some initial screening for glycosylation reaction. Until now we have achieved these goals as per the plan. We have synthesized few sugar derivatives such as tribenzyl glucal, triacetyl glucal/galactal as donors and 2,3,4-tri-O-benzyl α-methylglucoside as acceptor required in this study. We also carried out the test reactions using these building blocks.

Strategy for Future Research Activity

In future, our aim will be to successfully carry out the incorporation of silyl functionality at the 2-position of the sugar derivatives and perform the stereoselective glycosylation. From the initial results it is evident that we need more diverse screening of the reaction conditions. For this purpose, we need to synthesize a library of armed and disarmed donors and primary/secondary hydroxyl groups as acceptors. After achieving highly optimized reaction condition, our plan is to get the preliminary results and publish it as a methodology.
Further, we will apply this methodology to the synthesis of antitumor agent mithramycin. In first few months, the sugar part of the mithramycin will be synthesized by using our developed methodology. The aromatic core will then be synthesized and glycosylated with the glycan. The complete synthesis of the mithramycin will be published at the end of the fellowship tenure.