Synthesis of potential radioprotective components from Chinese herb drug Rhizoma Chuanxiong (rhizome of Ligusticum chuanxiong Hort., Umbelliferae)

The ethanolic extracts of some Chinese traditional herb drugs, reported by Hong-Fu Wang et al. in China, could inhibit platelet aggregation as well as protect against radiation damage in mice, rat and rabbits. The inhibitory effects of the extracts of five Chinese drugs on the rate of platelet aggregation were observed in both in vitro and in vivo tests, averaging 23-53% in vitro and 46-69% in vivo. Antiradiation tests on mice vs. 7.5-8.0 Gy of {dollar}gamma{dollar}-radiation, using the herb drug extracts as protective agents, showed increasing survival rates by 8-50%.; Based on Hong-Fu Wang's report, a search for the active constituents of these herb drugs in inhibiting platelet aggregation and protecting animals against radiation damage was started. In this research program, a Chinese traditional drug, Rhizoma Chuanxiong (rhizome of Ligusticum chuanxiong Hort.) was chosen. Three types of chemicals present in Rhizoma Chuanxiong, appeared promising for testing: 1-(5-hydroxymethyl-2-furyl)-9H-pyrido-(3,4-b)indole, 4-hydroxyl-3-butylidenephthalide and 5-hydroxyl-3-butylidenephthalide, and 4-hydroxyl-3-methoxycinnamyl 4-hydroxyl-3-methoxycinnamate. A total of 56 compounds of these derivatives has been synthesized and 30 were synthesized for the first time. The 30 compounds are: 1-phenyl-9H-pyrido-(3,4-b)indole, 1-(2-pyridyl)-9H-pyrido-(3,4-b)indole, 1-(5-methyl-2-furyl)-1,2,3,4-tetrahydro-9H-pyrido-(3,4-b)indole, 1-(5-methyl-2-furyl)-9H-pyrido-(3,4-b)indole, 1-{dollar}(5 {dollar}-hydroxymethyl-2-furyl)-9H-pyrido-(3,4-b)indole, 1-(2-thienyl)-1,2,3,4-tetrahydro-9H-pyrido-(3,4-b)indole, 1-(2-thienyl)-9H-pyrido-(3,4-b)indole, 1-(5-methyl-2-thienyl)-1,2,3,4-tetrahydro-9H-pyrido-{dollar}(3,4{dollar}-b)indole and 1-(5-methyl-2-thienyl)-9H-pyrido-{dollar} (3,4{dollar}-b)indole; 4-methoxy-3-propylphthalide, 4-hydroxy-3-propylphthalide, (Z)-4-methoxy-3-propylidenephthalide, 5-methoxy-3-propylphthalide, 5-hydroxy-3-propylphthalide, (Z)-5-methoxy-3-propylidenephthalide, 5-methoxy-3-butylphthalide, 5-hydroxy-3-butylphthalide, (Z)-5-methoxy-3-butylidenephthalide; 2,3-dimethoxycinnamyl alcohol, 2,5-dimethoxycinnamyl alcohol, 3-isopropoxycinnamic acid, methyl 3-isopropoxycinnamate, 3-isopropoxycinnamyl alcohol, 4-isopropoxycinnamic acid, methyl 4-isopropoxycinnamate, 4-isopropoxycinnamyl alcohol, trans-2,3-dimethoxycinnamyl, trans-2,3-dimethoxycinnamate, trans-2,5-dimethoxycinnamyl trans-2,5-dimethoxycinnamate, trans-3-isopropoxycinnamyl trans-3-isopropoxycinnamate, and trans-4-isopropoxycinnamyl trans-4-isopropoxycinnamate. The structure elucidation of these compounds was based o n IR, {dollar}sp1{dollar}H NMR and elemental analysis.; From this research program, a very mild dehydrogenation method was developed. It was by using 2,3-dichloro-5,6-dicyanobenzoquinone in acetonitrile at ice bath temperature to dehydrogenate 1-(5-hydroxymethyl-2-furyl)-1,2,3,4-tetrahydro-{dollar} 9{dollar}H-pyrido-(3,4-b)indole into 1-(5-hydroxymethyl-2-furyl)-9H-pyrido-(3,4-b)indole.; This project showed for the first time that harmanoid alkaloids have the activity of inhibition of platelet aggregation. The tested compounds increased the inhibitory rate of platelet aggregation by 4 to 23 times that of aspirin. These results aid in establishing a relation between radiation protection in animals and prevention of platelet hyperaggregation.