Tetrahydro Carbazole Ketone And Indole And The Synthesis Of Carbazole Compounds

The indolocarbazole alkaloids are a strucurally rare, but biologically interesting class of natural products, whose history dates back to 1977 with the isolation of staurosporine by Omura. In the subsequent years, many additional indolocarbazole alkaloids have been discovered. The indolocarbazole alkaloids are extremely interesting owing to the wide range of biological activities including antimicrobial, hypotensive, antifungal, and inhibition of platelet aggregation. The greatest interest in these compounds, however, has been due to their potent antitumor activity and as potent inhibitors of protein kinase(PKC). So we think it significant to synthesis indolocarbazole compounds as a access to indolocarbazole alkaloids. Synthetic strategies were employed to prepare the indolocarbazole compounds as well as the key intermediate 1 -oxotetrahydrocarbazole compounds. Since we found for the first time that reaction of 2-aminocyclohexanone and substituted arylhydrazines, via Fischer Indole Synthesis and hydrolysis,can directly lead to the preparation of 1-oxotetrahydrocarbazole compounds, we selected the synthetic route of 1-oxotetrahydrocarbazole as the intermediate material, upon cyclization with arylhydrazine to get indolocarbazole. 1-oxotetrahydrocarbazole compound is also the functionalized intermediate for the carbazole alkaloids. emphasised research were carried out as to probe new ways to synthesis 1-oxohydrocarbazole as well as best reaction conditions. Finially we succeeded to find a general procedure to prepare 1-oxohydrocarbazole starting from 2-aminocyclohexanone. In conclusion, with 2-aminocyclohexanone and substituted arylhydrazines as the starting materials, almost all can be cyclized to corresponding oxotetrahydrocarbazoles, except the reaction of 2-aminocyclohexanone and 4-methoxylphenylhydrazine directly resulted 1,10-dimemoxyl-indolocarbazole. As a result, we synthesized 12 1-oxohydro -carbazole compounds .With 1-oxohydrocarbazole compounds as the raw materialreacting with substituted arylhydrazines we obtained 6 indolocarbazole compounds.We also developed the synthetic route of Pam3Cys(tripalmitoyl-S-glyceryl cysteine). Pam3Cys is derived from the N-terminal part of bacterial lipopeptides and is a polyclonal B-lymphocyte and macrophage activator. Derivatives of Pam3Cys constitute highly potent, nontoxic immunoadjuvants, and lipopeptide-antigen conjugates have found important applications as novel fully synthetic low-molecular-weight vaccines. The total synthesis of Pam3Cys has been reported: Starting from cystine di-tert-butyl ester, via acylation and reduction to N-palmitoyl-cysteine tert-butyl ester, then S-alkylation with racemic 3-bromo-l,2-propanediol followed by esterfication with palmitic acid in the presence of dicyclohexyl -carbodiimide/dimethylaminopyridine and deprotection with trifluoroacetic acid. We mainly improved the reduction step via Zinc dust in 5% acetic acid instead of the costly reduction reagent dithioerythritol. Some other steps have been developed as well. The total yield has increased from 12.2% to 22.6%.