The Syntheses Of Alkaloid Harmicine And (S)-Glyceraldehyde Acetonide And Pictet-Spengler Reaction Of L-tryptophan Methyl Ester Hydrochloride With Ketones

This assay contains the following three parts:(1) Total synthesis of β-carboline alkaloid Harmicine:β-Carboline alkaloid Harmicine has shown various biology activities, so it is significant to develop a new synthetic route to Harmicine. We designed and studied a novel synthetic route in this thesis, by using tryptamine as the starting material, harmicine was obtained via eight steps in26%overall yield. Treatment of tryptamine with L-dibenzoyl tartaric acid anhydride gave amide1-27in92%yield. Cyclization of compound1-27in acetic acid produced imide1-28in87%yield. Selective reduction of compound1-28with sodium borohydride provided compound1-29. When compound1-29was treated with trimethylchlorosilane, Pictet-Spengler reaction occurred to give β-carboline1-30. Deprotection of benzoyl groups in ammonia provided compound1-31in90%yield. Exposure of compound1-31with methylsulfonyl chloride and triethylamine furnished compound1-32in81%yield. Reductive hydrogenolysis with Pd/C and triethylamine afforded compound1-19in79%yield. Finally, compound1-19was treated with lithium aluminium hydride to afford desired compound (R)-I-lin86%yield.(2) Preparation of (S)-Glyceraldehyde acetonide:(S)-Glyceraldehyde acetonide is an important intermediate, so it is wildly used in the synthesis of chiral drugs. We developed a novel synthetic route in this thesis, by using inexpensive L-arabinose as chiral material,(S)-glyceraldehyde acetonide was obtained via five steps in49%overall yield. Treatment of L-arabinose with compound Ⅱ-3, Wittig reaction took place to give compound Ⅱ-4in79%yield. Protecting the dihydroxyl group with acetonide of compound Ⅱ-4provided compound Ⅱ-5in89%yield. At last, treatment of compound Ⅱ-5with sodium periodate afforded desired compound Ⅱ-1b in75%yield.(3) Preparation of1,1-disubstituted tetrahydro-β-carbolines:The Pictet-Spengler reaction of tryptophan esters with ketones are usually hard to take palce, and the yields of the reaction are low. We found that this reaction could take place smoothly in DMF at110℃to produce a series of1,1-disubstituted tetrahydro-β-carbolines (Ⅲ-3a～Ⅲ-3j) in63%-91%yields.