Study On Total Synthesis Of Special Carotenoid Deinoxanthin

Deinoxanthin is the most abundant carotenoid contained in Deinococcus radiodurans,and is stood out to act as a special pigment with many biological activities,such as active oxygen scavenging or DNA protecting reagent.To the best of our knowledge,no synthesis of Deinoxanthin has been described in the literature.Herein,we explored the total synthesis of this special carotenoid,which was divided into the core C,Burke borate BSk and BSt,and the appendage A.To synthesize core C,we firstly optimized the synthetic method of 2-hydroxyl-α-cyclogeraniol.Geraniol epoxide was synthesized from geranyl acetate by Sharpless asymmetric dihydroxylation and methylsulfonyl chloride-assisted epoxidation.After the optimization of Lewis acids and protecting groups for hydroxy of geraniol epoxide,we discovered that the intermediate with hydroxyl protected by TMS could be promoted cyclization efficiently by 1 eq.Lewis acid of FeCl₃ or ZrCl₄.Compared with other literatures,this exploration could provide a better method to synthesize desired 2-hydroxyl-α-cyclogeraniol.In addition,we speculated that the transition state of Zr-O six-membered ring facilitated the cyclization.After selective hydroxyl protection,epoxidation and ring-opening,2-hydroxyl-α-cyclogeraniol converted to chiral alcohol C₉ which is the precursor to the core C.In the synthetic process of fragment A,2-methylpent-4-yn-2-ol was prepared by the addition of aluminum reagent generated from propargyl bromide with acetone.By the addition of tributyltin hydride and iodination,2-methylpent-4-yn-2-ol was transformed to target tail fragment A₁₀.In the post-processing of iodination,the usage of KF solution for washing the fragment A₁₀ could efficiently reduce the content of organotin impurities.When the addition of 2-methylpent-4-yn-2-ol with cyclopentadienyl zirconium,the presence of organotin impurities in A₁₀ also could be totally avoided.However,the yield of this method is low.Considering the structure of building block in polyene chain in target molecule,we synthesized the novel building block BSk by Stille coupling,and used（E）-3-（trimethylsilyl）but-2-en-1-ol as key intermediate to synthesize BSt.During the preparation of BSt,we firstly disclosed the relationship between cyclopentadienyl zirconium addition-TMS substitution concerning 2-butyn-1-ol with the dissolving capacity of THF and ether,which would affect the reaction obviously.In summary,the precursor of core C,terminal fragment A,Burke borate BSk and BSt have been synthesized successfully,which will establish the foundation for the total synthesis.