Stereoselective syntheses of 1,4-dideoxy-1,4-imino-octitols and novel tetrahydroxyindolizidines.
A new route for the preparation of four new indolizidines, (1R,2S,6S,7S,8aS)- and (1R,2S,6R,7R,8aS)-1,2,6,7-tetrahydroxyindolizidine (30 and 32) and (1S,2R,7S,8S,8aR)- and (1S,2R,7R,8R,8aR)-1,2,7,8-tetrahydroxyindolizidine (44 and 46), is reported. The synthesis is based on Knoevenagel homologation of the readily available enantiomerically pure pyrrolidin-carbaldehydes 13 and 37followed by asymmetric dihydroxylation of the subsequent alkenyl pyrrolidines and cyclization of the corresponding imino-octitols. The new indolizidines and their precursors (imino-octitols 20, 25, 26) and indolizidinones 28a and 28b have been tested for inhibitory activities toward 26 glycosidases. The enzymatic inhibition of trans-7-hydroxy-d-(-)-swainsonine (44) toward alpha-mannosidases is similar to that described for trans-7-hydroxy-l-(+)-swainsonine (11b) toward naringinase (alpha-l-rhamnosidase from Penicillium decumbens).
Departamento de Química Orgánica, Facultad de Química, Universidad de Sevilla, Apartado 553, Spain.
Ana T
AT
Carmona
José
J
Fuentes
Inmaculada
I
Robina
Eliazar Rodríguez
ER
García
Raynald
R
Demange
Pierre
P
Vogel
Ana L
AL
Winters
D002384:Catalysis; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D006026:Glycoside Hydrolases / Q000037:antagonists & inhibitors*; D007202:Indicators and Reagents; D007211:Indoles / Q000138:chemical synthesis* / Q000494:pharmacology; D015394:Molecular Structure; D010407:Penicillium / Q000201:enzymology*; D011759:Pyrrolidines / Q000138:chemical synthesis* / Q000494:pharmacology; D017026:Swainsonine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology
D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; D007211:Indoles; D011759:Pyrrolidines; D006026:Glycoside Hydrolases; D017026:Swainsonine