Four stereoisomeric ethyl esters 6a-d of the debromo-aglycone of surugatoxin (1) were synthesized. Individual treatment of the cis-diols 4β and 4α with borane-pyridine complex in AcOH followed by hydrogenolysis (H2/Pd-C) of the resulting monools 5c and 5d gave isomeric surugatoxin analogues 6c and 6d, respectively. Heating 5d (or 5c) in 90% trifluoroacetic acid at 60°C for 6 h resulted in the formation of an equilibrium mixture of desired natural surugatoxin analogue 6a (30%) and its C4-epimer 6b (3%) together with a 3, 4-dehydrated derivative 7 (50%). However, the equilibrium was unfavorable for the natural isomer 6a, the yield of which was raised up to 65% by recycling the recovered dehydrated derivative 7 and 6b.
