Studies On The Asymmetric Synthesis Of Marine Product Didemnaketal A

The Didemnaketals are a family of marine natural products which exhibited significant inhibition of HIV-1 protease.Until now,there is no successful report on the total synthesis of the Didemnaketals.On the basis of our previous work,we redesigned the synthetic route and finished the asymmetric synthesis of the skeleton of Didemnaketal A effectively.This dissertation mainly contains two parts.1.We made effort to optimize the route to C9-C16 portion of Didemnaketals.By modifying the functional groups and protecting groups of C1-C8 and C9-C16 portions, the C1-C16 portion of Didemnaketals was achieved via a Julia coupling of C1-C8 portion with C9-C16 portion.But we had to give up this synthetic route because of its poor efficiency.2.A novel synthetic route to the asymmetrical synthesis of Didemnaketal A was designed and carried out successfully after great effort,which was the vital foundation for this total asymmetric synthesis of Didemnaketal A,and involved four segments mentioned bellow.Firstly,by using the key Brown asymmetric crotylation and Takai reaction,the C3-C8 portion with two stereocenters and a(E)-C=C bond was successfully achieved in 7 steps with 24.7%total yield from 1.3-propanediol.Secondly,the C9-C16 portion of Didemnaketal A was synthesized through two separate routes.The better one involved the key Schenck-ene reaction and Sharpless asymmetric dihydroxylation,by which the C9-C16 fragment with three stereocenters and a C=C bond was constructed successfully in 5 steps with 26.0%total yield from (S)-citronellol.Thirdly,The synthesis of the C17-C22 portion was carried out through 9 steps with 30.2%total yield from the commercial available chiral synthon(R)-2-methyl-5, 5-diphenylpent-4-en-1-ol.In this approach three stereocenters,a protected carbonyl as well as a sulfonyl well constructed via key Wittig reaction and Sharpless asymmetric dihydroxylation. Fourthly,the C9-C22 portion was achieved via a Julia reaction of C9-C16 portion and C17-C22 portion,and then a final Suzuki-miyaura coupling of C3-C8 portion and C9-C22 portion was carried out to yield the skeleton of the Didemnaketal A with 22 carbons-contained chain as well as 12 stereocenters(5S,6S,7R,8R,10S, US,12S,14S,16S,18R,20S,21S)through 19 steps with 2.73%total yield.