Model studies of histrionicotoxin. The synthesis of the 1-azaspiro[5.5]undecane rings system from carbohydrate starting materials

Abstract

The base-catalysed condensation of nitroethane with dimethyl-t-butylsilyl 2,3-O-isopropylidene-α-D-lyxopentodialdo-1,4-furanoside (2) gives a diastereoisomeric mixture of nitro alcohols, which on desilylation with fluoride ion in tetrahydrofuran rearranges stereospecifically to 1L-[1,2,5/3,4,6(NO₂)]-3,4-O-isopropylidene-6-methyl-6-nitrocyclohexane-1,2,3,4,5-pentaol. The analogous condensation of the tetrahydropyranyl ether of 5-nitropentan-1-ol with aldehyde (2) and the subsequent desilylation and rearrangement occur similarly although the degree of stereoselectivity is lower. The major product, 1L-[1,2,5/3,4,6(NO₂)]-3,4-O-isopropylidene-6-nitro 6-[4′-(tetra hydropyranyloxy)butyl] cyclohexane -1,2,3,4,5-pentaol (9), is converted into (6S,7R,8R,9R,10R,11S)-7,8,11-tri-o-acetyl-9,10-o-isopropylidene-1-azaspiro[5.5]undecane-7,8,9,10,11-pentaol (13), which has the ring skeleton of histrionicotoxin (1).