| Traditional cytotoxic drugs play a very important role in drug therapy of cancer. Using cytotoxic natural products as lead compound to discover antitumor drugs with stronger and wider cytotoxicity is the key to drug therapy.Sinapyl alcohol derivatives is a kind of phenylpropenyl alcohol with 3, 5-position substituted by methoxy and 4-position substituted by hydroxyl. Sinapyl alcohol derivatives is wide spread in many kinds of species, and it belongs to phenylpropanoid derivatives. Previous investigations indicated that sinapyl alcohol derivatives exhibited strong cytotoxicity. Thus, we modified the structures of sinapyl alcohol derivatives and designed two series of target compounds of different structure to seek for more cytotoxic compounds. Besides, a new route for the synthesis of sinapyl alcohol derivatives was designed.Caffeic acid phenethyl ester (CAPE), which was isolated from Hungarian propolis, is a well known constituent with interesting biological properties. CAPE exhibited significant cytotoxic effect against various tumor cell lines and also possessed inhibitory activity against HIV-lintegrase. Sintenin, a cytotoxic natural ester, is one kind of CAPE-like analogue. Synthesis of sintenin and its derivatives, was carried out by a convenient path. To examine the SAR of this type of ester, all of the synthetic compounds were passed through the cytotoxicity screenings on six human tumor cell lines.Furthermore, another kind of neolignans with new skeleton was designed, and its structure is not reported in previous literature.This paper was divided into 5 chapters. Chapter 1 reviewed the development of antitumor drugs with cytotoxicity. Chapter 2 and 3 reported the synthesis of sinapyl derivatives and CAPE-like analogues, respectively. Chapter 4 reported the synthesis of lignins with new skeleton, and chapter 5 discussed the SAR of the CAPE-like analogue synthesized. Totally 46 target compounds and intermediates were synthesized, including 41 new compounds. |
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