A ROUTE TO SEVERAL STEREOISOMERS OF CASTANOSPERMINE

The following three stereoisomers of castanospermine have been prepared: (1R,6R,7R,8S,8aR)-1,6,7,8-tetrahydroxyindolizidine (1), (1R,6S,7S,8S,8aR)-1,6,7,8-tetrahydroxyindolizidine (2), and (1R,6R,7S,8S,8aR)-1,6,7,8-tetrahydroxyindolizidine (3). Each of these compounds was synthesized via asymmetric allylation of pentose derivatives with [(Z)-gamma-(methoxymethoxy)allyl]diisopinocampheylborane, an approach which is, in principle, suitable for preparations of a total of eight stereoisomers of castanospermine. Compounds 1-3 were tested as possible inhibitors of various glycosidase enzymes and for anti-HIV-1 activity in cell cultures. They are very poor inhibitors of glycosidase enzymes; however, preliminary tests indicate indolizidines 1 and 3 have weak but significant anti-HIV activities.