Synthesis Of Important Intermediates Of Vinigrol

Vinigrol is a tricyclic diterpenoid isolated from the mold of Virgaria nigra F-5408.It consists of two cis-decahydronaphthalene rings and an eight-membered bridge ring,eight consecutive chiral centers.Three hydroxyl groups.Vinigrol has anti-hypertension,inhibits platelet aggregation,shrinks mouse aortic smooth muscle,antibacterial,and antagonizes tumor necrosis factor and other biological activities.Vinigrol has a complex chemical structure and many biological activities,so it has become a hot spot for chemists and pharmaceutical chemists in recent years.The research work in this paper mainly includes the following aspects: 1)The progress of chemical structure,biological activity and total synthesis of Vinigrol is summarized.2)Inverse synthesis analysis of Vinigrol,due to the complexity of the entire synthetic route of Vinigrol,the work of this paper is to synthesize important intermediates of Vinigrol((1R,4R,4AS,7S,8AR)-9-(1-hydroxy-3-A)Butyl)-4a-methoxy-4-methyl-7-((trimethylsilyl)oxy)-1,2,3,4,4a,7,8,8a-octahydro-1,7-ethoxy-10-ketone).3)The synthetic route of important intermediates of Vinigrol was designed and synthesized.4)Experimental results: The Vinigrol skeleton structure was constructed by the reaction of 1,4 addition reaction,Wittig reaction,Michael addition reaction and Aldol reaction with p-bromophenol as the starting material,and finally by the addition reaction with isovaleraldehyde.The synthesis of important intermediates of Vinigrol was completed.The innovation of this paper is to realize the ring closure by Michael addition reaction and Aldol reaction tandem cyclization.A total of 21 compounds were synthesized,18 of which were the first reported new compounds.