The Chiral Building Blocks Derived From D-Mannose And Synthesis And Configurations Of (-)-furosongin-1 And (+)-Dihydrofurospongin-2

Sponges around the world a wide range of compounds isolated from the sponge out of having a variety of biological activity, such as HIV protease inhibitors, HIV reverse transcriptase inhibitor, anti-bacterial, immunosuppressive and anti-tumor activity and so on. In 1971, Cimino and the like sponges Spongia officanalis Hippospongia communis isolated from the resultant(+)-Furospongin-1, its skeletal structure through a large number of NMR experiments confirmed that it is composed of two furan ring, a 7,8-trans position straight-chain molecule consisting of a double bond, two chiral centers are located in C-11-bit and the C-13, on the two chiral centers absolute configuration has been controversial, since 1971, both the absolute configuration type from the initial(11S, 13R) to(11S, 13S) and then to(11R, 13S), but modification in accordance with the literature given are based on speculation, the results were not convincing, so by chiral synthesis methods to determine the absolute configuration is necessary. In this paper, D-mannose as the chiral source,complete the following tasks:1. Starting from the D-mannose, after seven-step reaction, with 21% overall yield get 5-membered lactone block, and block the lactone intermediate, the reduction ring-opening selectivity halo, Mitsunobu, off acetone fork, cut vicinal diol, Wittig, into ethylene, CM reactions, completed 15 hand block(2-8—2-17)synthesis. The yield is above 70%.2. Developed by the five-membered lactone block 2-8, via nucleophilic addition of acetylenic anions, hydrogenated to hydroxyl, deacetone fork, cut vicinal diol, Ts off ethylene, Julia-Kocienski first total synthesis of other reactions natural product(+)- Furospongin-1 enantiomer of(-)- Furospongin-1;the(-)- Furospongin-1 after the oxidation to give DMP natural product(-)-enantiomer of Dihydrofurospongin-2(+)- Dihydrofurospongin-2; then the(+)-Dihydrofurospongin-2 with Na BH4 reduced to give the chiral C-11 hydroxyl group of a pair of non enantiomer, after carbon spectral data compared to determine one of diastereoisomers isomer is synthesized in this paper(-)-Furospongin-1, another non-enantiomer is a natural product(+)- enantiomer of the non-Furospongin-1, thereby determining the natural product(+)-Furospongin-1 is the correct absolute configuration(11R, 13S), to resolve the decades there has been controversy configuration;3. In the 2,3,5,6-Di-O- isopropylidene-D-mannose α position hydroxymethyl reaction, by-products of structural identification, presumed mechanism byproduct,and draw PH value reduce the most critical factors that hinder the reaction, the successful development of an effective method of maintaining system PH value =10 for the preparation of chiral quaternary carbon target, the traditional method requires only reaction 48 h,1 h 40 min to complete the literature method,5-fold lower amount of formalin, paraformaldehyde reduced production, thereby improving the efficiency of the column chromatography, post-treatment significantly simplified.