GENERAL ENTRY TO THE 3,5-DISUBSTITUTED INDOLIZIDINE CLASS OF DENDROBATID ALKALOIDS - TOTAL SYNTHESES OF BOTH ENANTIOMERS OF INDOLIZIDINES 195B, 223AB, 239AB, AND 239CD FROM A COMMON CHIRAL SYNTHON

A general protocol for the total syntheses of both enantiomers of dendrobatid alkaloids, indolizidines 195B, 223AB, 239AB, and 239CD, belonging to the 3,5-disubstituted indolizidine subclass is described, in which 3,4-dideoxy-D-threo-hexitol (8) has been used as a single and common chiral synthon. The syntheses of the (+)- and (-)-enantiomers of these alkaloids begin with (S,S)- and (R,R)-1,2:5,6-diepoxyhexanes (7), respectively, both of which were derived from 8 in three steps and are carried out by way of pyrrolidine formation via the cyclic sulfates leading to the (2R,5R)- and (2S,5S)-trans-2,5-dialkylated pyrrolidines, which were converted to the (+)- and (-)-enantiomers, respectively, of the title indolizidine alkaloids. These syntheses involve the first chiral preparations of indolizidines 239AB and 239CD both in natural (-)- and unnatural (+)-enantiomeric forms, which confirm the absolute configurations of natural 239AB and 239CD as 3R,58,8aR and 3R,5R,8aR, respectively.