TREMORGENIC INDOLE ALKALOIDS .9. ASYMMETRIC CONSTRUCTION OF AN ADVANCED F-G-H-RING LACTONE PRECURSOR FOR THE SYNTHESIS OF PENITREM-D

Lactone (+)-12 is envisioned as the precursor to the F-G-H rings of pe nitrem D (4) in our ongoing synthetic venture. The efficient, stereoco ntrolled introduction of the vicinal quaternary methyl groups present the major challenge in the construction of this subunit. Our first rou te to (+/-)-12 was marked by low overall yield (<2%) and the instabili ty of several key intermediates; these deficiencies were rectified in a second-generation approach that produced optically active material ( 18 steps from 19a, 2.1% overall). The successful strategies exploited enolate generation via either conjugate additions to alpha,beta-enones or the Evans oxy-Cope rearrangement as key regiochemical control elem ents.