Studies On The Total Synthesis Of Hainanolide

The natural product, hainanolide I, demonstrated antitumor and antiviral activities in preliminary test. There are six rings and seven chiral centers in the molecule. The synthesis of tricyclic compound 15 through an intermolecular Diels-Alder reaction had been reported. In this thesis, further investigation on the construction of hainanolide has been carried out. Introduction of the C₃-β, C₄-α-dihydroxy groups on the ring C and assembling the lactone ring E between C₃-β-hydroxy group and C_5a-β-carboxylic acid group and decarboxylation of C,-carboxyl ester group were taken place in the meantime. The content of this thesis mainly consists of following three parts:â… . Introduction of the C₃-β, C₄-α-dihydroxy groups on the ring C:a. The correction of the structure of compound 20a, which was assigned as lactone by Yu.b. The new seven steps synthesis rout for conversion of C_2a-α-H of compound 11a to C_2a-β-H was designed and carried out. The yield of the compound 15 from lla was improved from 22% to 34%.c. Reduction of compound 20, instead of expected C₄-α-OH compound, C₄-β-OH product 26 was obtained. Compound 26 in acidic condition easy proceeded ring closure with C_5a-β ester group to form lactone 27.d. C₄-α-OH compound 29 was obtained by reduction of enol ether 28 with BH₃.e. Protection C₄-α-OH group of compound 15 and 40 with MOM group gave the compound 34, 44 respectively.â…¡. Assembling the lactone ring E between C₃-β-hydroxy group and C_5a-β...