Substitution Reaction Based On 1,2-Bissulfonyl Vinyl And Its Application Of Protein Labeling

Sulfonyl vinyl compounds are important functional components which are widely used in organic synthesis and biomolecules.In the field of organic synthesis,sulfonyl groups can be used as a good leaving group for a series of radical reactions.Olefin is an unsaturated hydrocarbon which is prone to addition reaction.Bissulfonyl vinyl combines the common properties of sulfonyl and olefin,and can undergo addition reactions,substitution reactions,rearrangement reactions.In the field of biomolecules,sulfonyl vinyl compounds can be used as electrophilic inactivators of protease small molecules,such as cysteine protease inhibitors,HIV-1 inhibitors and transpeptidase inhibitors.In addition,unsaturated sulfonyl compounds are also important bioactive substances in pharmaceutical chemistry,which can be used as neuroprotective agents in the treatment of Parkinson’s disease and synthesis of anti-trypanosoma drug reagents.In addition,the study of sulfonyl vinyl compounds in protein probe oxidation modification markers is still a great challenge.Cysteine sulfonic acid is a peroxidation product of proteins and a key regulator of protein function,catalysis and signaling.The study of protein oxidation modification is mostly carried out by qualitative and quantitative detection of cysteine oxidation products.There are indirect and direct methods for the study of protein oxidative modification and cysteine sulfinic acid.The indirect method is to pre-treat the products after protein oxidation use thiol blockers and reducing agents,and then use specific reagents for detection.In this method,the protein pretreatment process takes a long time,and the protein internal microenvironment is prone to change,which promotes the appearance of false positive and leads to oxidative stress.The oxidation state of cysteine sulfonic acid is not stable enough,and easy to cause false positive results.The direct method is to develop specific small molecule probes with high sensitivity and low toxicity,but the reported small molecule probes have few reaction types and low efficiency,and it is difficult to achieve rapid and efficient detection.In order to better solve the above problems,we explored the substitution reaction and biological application of 1,2-bissulfonyl vinyl,constructed a new sulfonyl vinyl substitution reaction without metal catalysis,and also realized the application of sulfonyl vinyl compounds in sulfhydryl protein subsulfonated modification marker.The specific work of this thesis is as follows.(1)Substitution reaction of 1,2-bissulfonyl ethylene and application of thiol protein oxidation modification markersWe developed a substitution reaction between 1,2-bissulfonyl ethylene and aliphatic sulfonic acid at room temperature,and realized the rapid and efficient reaction between sulfonyl and aliphatic sulfonic acid.A fast and efficient reaction between bissulfonyl vinyl and sodium aliphatic sulfonate to produce asymmetric sulfonyl vinyl was achieved.Meanwhile,the reaction of 1,2-bissulfoyl ethylene with cysteine sulfonic acid was realized by using the same conditions and methods,and 1,2-bissulfoyl ethylene was successfully used as a probe marker for oxidative modification of proteins.(2)Hydroxylation substitution reaction of 1,2-bissulfonyl ethylene with sulfonic acidWe have developed a new organic reaction for the synthesis of functionalized aliphatic aldehydes from 1,2-bissulfonyl vinyl by hydroxylation substitution of enol taustry-assisted substitution of 1,2-bissulfonyl vinyl with trace water in solvent under heating condition.The reaction is provided by sodium benzenesulfonate alkaline environment,mild reaction conditions,green solvent environmental protection,no metal catalysis and inert gas protection.At the same time,a new sulfonyl alcohol compound was obtained by one-pot reduction,and its synthesis method has not been reported before.Hydroxyl and sulfonyl groups of this compound are important functional groups in drug synthesis,so it may have potential value for biological and pharmaceutical research.