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Two aldonolactones and an aldonic acid methylester were used in the synthesis of three stereoisomeric 1,5-dideoxy-1,5-imino-pentitols with ribo-, L-lyxo- (L-arabino-), and xylo-configuration. The aldonic acid derivatives were mesylated at C-5 and subsequently reacted with ammonia. The corresponding lactams were reduced with sodium acetoxyborohydride or borane dimethyl sulfide to the 1,5-imino-1,5-pentitols.1,2,5-Trideoxy-1,5-imino-D-erythro-pentito l and 1,2,5-trideoxy-1,5-imino-D-threo-pentitol were synthesised from 2,5-difunctionalised aldonolactones by reduction of the 2-functionality with hydrazin. The hereby formed 5-functionalsed 2-deoxy-lactones were then reacted with ammonia to give the corresponding lactams. The lactams were reduced by borane dimethyl sulfid or lithium aluminium hydride to the 1,2,5-trideoxy-1,5-imino-pentitols.2,5-Difunctionalised aldonolactones were also used for synthesis of four stereoisomeric 2-amino-1,2,5-trideoxy-1,5-imino-pentitols with D-xylo-, L-xylo-, D-ribo-, D-arabino-configuration. The pentitols were obtained by reduction of the corresponding 2-amino-lactams with borane dimethyl sulfid. The lactams were formed by reaction of 2,5-difunctionalised aldonolactones with ammonia. The reaction led to 2,3-epoxides and 4,5-epoxides as intermediates which were opened selectively at C-2 and C-5 by ammonia, selectively.5-Amino-2,3-O-isopropylidene-4-O-methanesulfonyl-1,5-l actams with D-ribo- and D-lyxo-configuration were treated with tetrabutyl ammonium cyanide dissolved in dimethyl formamide. The reaction led to formation of 4-amino-5-C-cyano-4,5-dideoxy-2,3-O-isopropylidene-L-lyxono-1,4-la ctam and 4-amino-5-C-cyano-4,5-dideoxy-2,3-O-isopropylidene-L-ribono-1,4-la ctam, respectively. The gamma-lactams were formed by ring contraction of the delta-lactams. The lactams were reduced with lithium aluminium hydride to the corresponding pyrrolidines with L-lyxo- and L-ribo-configuration.5-Bromo-2,5-dideoxy-D-threo-pentono-1,4-lacto ne and 5-bromo-2,5-dideoxy-D-erythro-pentono-1,4-lactone were methylated at C-2 by treatment with lithium hexamethyl disilazane followed by methyliodide. The 5-Bromo functionality was then substituted by azid, which was hydrogenated in presence of palladium on carbon. The amino-lactones rearranged to the corresponding lactams, that could be reduced to 1,2,5-trideoxy-1,5-imino-2-C-methyl-D-arabinitol, hydrotosylate and 1,2,5-trideoxy-1,5-imino-2-C-methyl-D-xylitol, hydrotosylate with lithium aluminium hydride.The epoxide in methyl 2,3-anhydro-5-O-p-toluenesulfonyl-beta-D-ribofuranoside was opened by diethyl aluminium cyanide with formation of methyl 3-C-cyano-5-O-p-toluenesulfonyl-beta-D-xylofuranoside. Hydrogenation of the nitrile function with palladium on carbon led to substitution of the tosyl group by the formed amine. The hereby formed pyrrolidine was isolated as an oxime.
|Place of Publication||Kgs. Lyngby, Denmark|
|Publisher||Technical University of Denmark|
|Number of pages||146|
|Publication status||Published - Jan 1998|