Synthesis of nucleotide, peptide and lipid containing molecular tools for life science studies

Sammanfattning: This thesis is based on five parts. The first and second chapters describes two synthetic routes, employing different protecting group strategies for synthesis of uridine 3'-(ethyl, 2-ethoxyethyl, 2-chloroethyl, 2,2-dichloroethyl and 2,2,2-trichloroethyl) phosphate. In the first synthetic route, uridine was protected with acid labile protecting groups, 4-methoxytetrahydropyran-4-yl for the 2'-OH group and 4-methoxytriphenylmethyl for the 5'-OH group. In the second synthesis route the tert-butyldimethylsilyl (TBDMS) was used for protection of the 2'- and 5'- hydroxyls. Silyl deprotection was performed using triethylamine trihydrofluoride.In the third chapter a method for O- and S-palmitoylation of non-protected peptides is described. The procedure consists of treatment of the peptides with excess of palmitoyl chloride in neat trifluoroacetic acid for 10 minutes at room temperature. The tripeptides Gly-Cys-Phe and Gly-Ser-Phe were S- and O-palmitoylated and the hydrophobic Pulmonary Surfactant Protein-C model peptides were converted to the respective S,S- and O,O-dipalmitoylated peptides.The production of S-citronellyl-L-cysteine and S-dolicyl-L-cysteines for use as mass spectrometry standards is described in chapter four. For formation of the thioether linkage, a mesylated citronellol and/or mesylated dolichols and L-cysteine ethyl ester were employed.Finally, in the last chapter a route for synthesis of 8-aminoadenosine 5'-(aminoalkyl phosphates), analogues of aminoacyl adenylates is described. The 5'-H-phosphonate of 2', 3'-O, O-benzylidene-8-bromoadenosine, with unprotected base was condensed with benzyloxycarbonyl (Z) protected amino alcohols (L-isoleucinol, L-histidinol and L-methioninol), in the presence of bis(2-oxo-oxazoline-3-yl)phosphonic chloride. After oxidation the 8-bromo was transformed into the 8-azido moiety by sodium azide in dimethyl sulfoxide. Deprotection of the benzylidene and benzyloxycarbonyl (Z) groups as well as reduction of the azido to the desired amino function was accomplished in a single step by catalytic transfer hydrogenation (palladium-carbon or palladium black in 80% acetic acid).