Application Of 1,1-thiochromone Photosensitive Group In Sugar Chemistry

The study of carbohydrates plays an important role in the understanding of life process,disease monitoring and disease treatment.Enough amount of structural well-defined carbohydrate samples is critical to the research in glycoscience.And chemical synthesis is a powerful tool for obtaining those samples and thus has attracted much attention.The concerns about the chemical synthesis of carbohydrates mainly include:Syntheses of sugar building blocks,Efficient construction of glycosidic bonds;Separation and purification of intermediates and target products.Protecting groups have effects on the above-mentioned three aspects.Manipulation of protection and deprotection is often required for chemical regiselectively synthesis of sugar building blocks.And in many cases,protecting groups are vital to control the stereoselectivity and yields of glycosilation via acyl participation and electronic effects.Moreover,protecting groups can be exploited as a tool to facilitate the process of separation and purification in carbohydrate synthesis.Protecting groups could be divided into classical protecting groups and photolabile protecting groups(PPGs)according to their deprotection methods.The deprotection of classical protecting groups usually takes place under chemical conditions using acidic,basic,oxidative or reductive reagents,while the deprotection of PPGs takes place under light conditions.Considering the difference in deprotection conditions,the removal of a PPG on carbohydrates may have high orthogonality with those classical protecting groups,and thus PPGs have a great potential in carbohydrate chemistry.2-(Hydroxymethyl)-3-phenyl-4H-sulfonylchromen-4-one has been reported as a PPG.However,this PPG's intensive studies haven't been conducted in carbohydrate chemistry.In this paper,we will explore their potentials in carbohydrate chemistry in the following aspects:a.to investigate their stability during the glycosylation process;b.to study their effects on the stereoselectivity of glycosylation;c.to explore the selective deprotection of the photolabile group in the presence of classical protecting groups.The followings have been done in this thesis:(1)Improvement of the PPG synthesis was conducted via a modified route of 2-(Hydroxymethyl)-3-phenyl-4H-sulfonylchromen-4-one;(2)Three PPG protected-glycosyl donors were synthesized:acetylated p-thiotolyl glycosyl donor with C-6 protected by PPG;benzylated p-thiotolyl glycosyl donor with C-6 protected by PPG;benzylated p-thiotolyl glycosyl donor with C-2 protected by PPG.(3)The stability of the PPG and its effect on stereochemistry of glycosylation were investigated.Glycosylation between the above-mentioned glycosyl donors and a acceptor was conducted in the presence of NIS/TfOH.As for the benzylated glycosyl donor with C-6 protected by PPG and C-2 protected by PPG,the corresponding glycosyl products were obtained in good yields,and the ratio of ?/? isomer is 1.4:1 and 20:1 respectively.The result showed that the photolabile group is stable under the glycosylation condition and the stereoselectivity of glycosylation could be controlled by the C-2 carbonated photolabile group via carbonate-mediated anchimeric assistance.The glycosyl yield for acetylated p-thiotolyl donor was low due to the acyl migration from the donor to the acceptor while the ratio of ?/? isomer greater than 20:1.(4)Substrate scope was investigated by using the C-2 PPG-protected donor coupled with various alcohols.The glycosylation underwent smoothly with primary,secondary and tertiary alcohols with high stereoselectivity(?:?=6.2:1?20:1)in 80%?97%yield,which again demonstrated the PPG's stereochemical control effect and its stability.(5)The selective deprotection of the photolabile group was studied in the presence of several different classical protecting groups.The PPG's deprotection was conducted in methanol in 70?86%yields under blue light irradiation for those glycosyl products with different type of classical protecting groups such as benzyl,benzoyl,silyl,acetal and allyl group.The results showed that all kinds of classical groups has high tolerance to the deprotection condition of the photolabile group.In conclusion,thiochromone 1,1-dioxide is stable enough and can be selectively deprotected as a photolabile protecting group during the synthetic process in carbohydrate chemistry.And it has great stereochemical control effect via anchimeric assistance using a donor with C-2 carbonated photolabile group.Thus,photolabile protecting groups should have the great potentials for further application in carbohydrate chemistry.