Studies On The Syntheses Of Natural Product-like Compounds From Oleanolic Acid

In this thesis, a series of natural prodcuct- like compounds of oleanolic acid with different structures in ring A and ring C were synthesized starting from abundant and inexpensive oleanolic acid(OA, 1). The AB- and DE-ring products of O A were also prepared via the ring C cleavage of OA. Besides, a series of Labdane-like compounds were synthesized using sclareolide as the model compound of AB-ring product.1. A series of oleanolic acid-like compounds 3?6 with a ring C structure of cyclohexanone, cyclohexenone, cyclohexadiene, or ring C opened triene etc. were synthesized starting from oleanolic acid via methylation of carboxyl group, acetylation of 3-OH, oxidation of 12-ene with O3, dehydrogenation with Br2/HBr, enol acetylation of carbonyl group, and ring opening with light irradiation. A series of oleanolic acid-like compounds 11?13 with a cyclohexenone structure in ring A or ring C were also synthesized through oxidation, dehydrogenation, and brominat ion of ring A or ring C.2. The AB-7 and DE-ring products 8 of OA were prepared by oxidation of the OA derivative bearing a conjugated triene structure with mCPBA/acidic catalyst. The AB- and DE-ring products are decalins with several chiral centers, which could be used as versatile synthons for the synthesis of natural product- like compounds of diterpenes.3. Using sclareolide as the model compound of the AB-ring product of OA, lactone opening reactions of aclareolide with Grignard reagent and organolithium reagent gave Labdane diterpene-like compounds 15?16 with a benzene or furan ring. Furthermore, the carbonyl group of compounds 15?16 was reduced to methylene with Wolff-K ishner-HuangMinlong reaction, providing compounds 17?19.4. All the compounds synthesized in this thesis were characterized by IR, MS, 1H NMR, and 13 C NMR.5. Bio-activity studies of Labdane diterpene- like compounds 14?19 show that compounds 15 and 18 with a furan ring have cytotoxic activity, while compounds 14, 16, 17, and 19 with a benzene ring have no cytotoxic activity.