Total Synthesis of Viridin,Viridiol and Nodulisporiviridin E

Author:Ji Yang

Supervisor:gao shuan hu

Database:Doctor

Degree Year:2019

Download:18

Pages:179

Size:8870K

Keyword:

Viridin belong to complex furanosteroids with promising antifungal activities.Their unique skeletons and condense arrays of stereogenic centers have attracted wide-spread interest from the synthetic community.In order to investigate their Structure-Activity Relationship(SAR)and associated mechanism-of-action,we developed new synthetic strategies,which led to efficient and enantioselective total synthesis of viridin,viridiol and nodulisporiviridin E.The concise total synthesis of furanosteroids natural products was achieved in 14 steps to 16 steps from easily available starting material.The synthesis of nodulisporiviridin E strategy provides a scalable and diverse approach to prepare the biogenetically and structurally related furanosteroids that will facilitate the following biological studies.1)Total Synthesis of Nodulisporiviridin EWe have achieved the first total synthesis of nodulisporiviridin E via a convergent strategy in 16 steps.In our synthesis,two coupling fragments of dihydroindenol and chiral six-membered ring were prepared first.Then,we used a substrate controlled intramolecular Heck reaction to set up the quaternary carbon center.Finally,nodulisporiviridin E was concurrently obtained after enhancement of the oxidation state and installing the furan ring.This convergent strategy provides a scalable and diverse approach to prepare the biogenetically and structurally related furanosteroids that will facilitate the following biological studies.2)Total Synthesis of Viridin and ViridiolWe have developed a general strategy to synthesize of furanosteroid viridian and viridiol was achieved in 14 and 15 steps.Comparing with previous work,this newly developed strategy used an easily available chiral pool(L-ribose derivatives)as the starting material which dramatically improve the overall synthetic efficiency.An intramolecular nitrile oxide-alkene cycloaddition was applied to construct the highly substituted D ring with the key chiral cis-triol fragment.A key Co-catalyzed hydrogen atom transfer(HAT)radical cyclization was successfully developed to form the C-ring as well as the all-carbon quaternary center at C-10.Installing the furan E ring and changing the oxidation state of the D ring would produce viridian and viridiol.