1 Department of Organic Chemistry, Technical University of Denmark2 Department of Chemistry, Technical University of Denmark
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.