The naphthalene derivative 4 was converted into the dinitro compound 5 by a 'double Mannich' reaction. Reduction of the compound 5 with tributylstannane gave the hydroxylamines 6 and 7 in low yield. Treatment of 5 with methanethiolate in DMSO gave the sulfides 8, 9 and/or 10 in varying ratios, depending on the reaction conditions. Raney nickel reduction of 10 gave the cytisine analogue 1. Similarly the dinitroquinoline 13 was converted into the dinitro compound 14. Treatment of 14 with sodium methanethiolate gave a mixture of the sulfides 15–17. Reduction of the compounds 16 and 17 with Raney nickel gave the pyridoazocine 2. The mechanisms of formation of the hydroxylamines 6 and 7 and the sulfides 8–10, 15–17 are discussed.

9-(4-Methylthiobutyl)adenine 7 has been prepared and shown to be a potent inhibitor of the enzyme methylthioadenosine nucleosidase.

Enantiospecific synthesis of (6S,7R,8R,8aR)-6,7,8- trihydroxyindolizidine ( 1-deoxy-castanospermine ) (3) is described from readily available D-glucose, where the key step involves oxidative bromination of a benzylidene acetal to afford 8-azido-3-o-benzoyl-5-bromo-5,6,7,8-tetradeoxy-1,2-o-isopropylidene-β-L-ido-octose (16). The synthetic indolizidine (3) was tested against a range of glycosidases.

AbstractThe title compound (X) can be synthesized starting from the D‐glucose derivative (I) via the intermediate (VI) as shown.

Enantiospecific syntheses of (6R,7S,8aR)-6,7-dihydroxy-indolizidine (3) and (6R,7R,8S,8aR)-6,7,8-trihydroxy-indolizidine (4) from methyl 2-azido-4,6- O -benzylidene-2-deoxy-α-D-altropyranoside (7) are reported. The two synthetic indolizidines (3) and (4) have been tested against a wide range of enzymes.

An enantiospecific synthesis of 1-deoxy-castanospermine (2) is described from D-glucose, where the key step involves oxidative bromination of a benzylidene acetal to afford 8-azido-3-O-benzoyl-5-bromo-5,6,7,8-tetradeoxy-1,2-O-isopropylidene-β-L-ido-octose (6).

Enantiospecific syntheses of (6R,7S,8aR)-dihydroxyindolizidine (1) and (6R,7R,8S,8aR)-trihydroxyindolizidine (2) from readily available methyl 2-azido-4,6-O-benzylidene-2-deoxy-α-D-altropyranoside (5) are described.

Periodate oxidation of 1,2-O-ethylene-β-d-fructopyranose and ring closure of the resulting dialdehyde with nitromethane afforded a mixture of four 4-deoxy-1,2-O-ethylene-4-nitrohex-2-uloses having the α-l-xylo, β-d-arabino, α-l-lyxo, and β-d-ribo configurations, together with two heptuloses which arose from products of the incomplete oxidation of the starting material. When nitromethane was in excess of the base used for the cyclisation reaction, the α-l-xylo-hexulose was the major product, but this could be isomerised substantially to the β-d-ribo-isomer when treated with excess sodium methoxide. Acetylation of the α-l-xylo-hexulopyranose, followed by reductive elimination of the acetoxy groups, afforded an approximately 1:1 mixture of (6R,10R)- and (6R,10S)-10-nitro-1,4,7-trioxaspiro[5.5]undecane. Acid-catalysed epimerisation of the (6R,10S) isomer afforded the (6S,10S) isomer. Oxidation of either the (6R,10R) or the (6R,10S) isomer with permanganate at pH 7 afforded the 10-one. This was reduced with sodium borohydride to give mainly (6R,10S)-1,4,7-trioxaspiro[5.5]undecan-10-ol, from which the OH group was removed to give enantiomerically pure (R)-1,4,7-trioxaspiro-[5.5]undecane.