| I. General Method for the Synthesis of Selectively N-Alkylated Polyamines. A versatile method is presented for the synthesis of linear polyamines--in particular the naturally ubiquitous putrescine, spermidine, and spermine--regiospecifically N-alkylated or -poly-alkylated. The approach is based on the acylation of appropriate amines with N-(trifluoroacetyl)amino acid chlorides, optional alkylation followed by selective saponification of the trifluoroacetylamino function, analogous reacylation, and polyamide to polyamine reduction.; II. A Short Synthesis of ((+OR-))-2-Amino-6,7-Dihydroxy-1,2,3,4-Tetra-hydronaphthalene (ADTN) and Its N-Methyl Derivative. A new, straightforward preparation of ADTN and N-methylADTN has been developed which is based on Friedel-Crafts acylation of veratrole by N-(trifluoroacetyl)aspartic anhydride. Subsequent deketonization of the adduct, intramolecular acylation, and a second ketone reduction yields 2-(trifluoroacetylamino)-6,7-dimethoxy-1,2,3,4-tetrahydronaphthalene. Deprotection at nitrogen followed by methyl ether cleavage gives the target ADTN; N-methylation prior to deprotection yields N-methylADTN.; III. Friedel-Crafts Acylation with N-(Trifluoroacetyl)Amino Acid Chlorides. Application to the preparation of (beta)-Arylalkylamines and 3-substituted 1,2,3,4-Tetrahydroisoquinolines. N-(Trifluoroacetyl)-(alpha)-amino acid chlorides react with benzene, anisole, and veratrole in the presence of AlCl(,3) to produce the corresponding aromatic ketones in fair to high yields. The amino-ketones are in general smoothly reduced with Et(,3)SiH in either CF(,3)CO(,2)H or BF(,3)(.)Et(,2)O to the coresponding N-(trifluoroacetyl)-(beta)-arylalkylamines. The latter are readily deacylated and converted to 3-substituted 1,2,3,4-tetrahydroisoquinolines by condensation with formaldehyde and HCl.; IV. Synthesis of 2-(8-Carboxyoctyl)Spermidine, A New Ligand For Affinity Chromatography and Radioimmunossay. A synthetic route to 2-(8-carboxyoctyl)spermidine, a C-substituted polyamine potentially valuable in affinity chromatography and radioimmunoassay, has been developed. Starting with t-butyl-10-undecylenate, successive reactions with p-toluenesulfonyl iodide, Et(,3)N, and KCN afforded t-butyl-10-cyano-10-undecylenate. Conjugate addition of putrescine and subsequent reduction of the nitrile functionality afforded a complex mixture of products presumably containing the t-butyl ester of 2-(8-carboxyoctyl)spermidine. |
