| Abstract
| - A new strategy for enantiospecific construction of the Securinega alkaloids has been developedand applied in total syntheses of (+)-14,15-dihydronorsecurinine (8), (−)-norsecurinine (6), andphyllanthine (2). The B-ring and C7 absolute stereochemistry of these biologically active alkaloidsoriginated from trans-4-hydroxy-l-proline (10), which was converted to ketonitrile 13 via a high-yielding eight-step sequence. Treatment of this ketonitrile with SmI2 afforded the 6-azabicyclo[3.2.1]octane B/C-ring system 14, which is a key advanced intermediate for all three synthetictargets. Annulation of the A-ring of (−)-norsecurinine (6) with the required C2 configuration viaan N-acyliminium ion alkylation was accomplished using radical-based amide oxidation methodologydeveloped in these laboratories as a key step, providing tricycle 33. Annulation of the D-ring ontoα-hydroxyketone 33 with the Bestmann ylide 45 at 12 kbar gave (+)-14,15-dihydronorsecurinine(8). In the securinine series, the D-ring was incorporated using an intramolecular Wadsworth−Horner−Emmons olefination of phenylselenylated α-hydroxyketone 47. The C14,15 unsaturationwas installed late in the synthesis by an oxidative elimination of the selenoxide derived fromtetracyclic butenolide 50 to give (−)-norsecurinine (6). The A-ring of phyllanthine (2) was formedfrom hydroxyketone 14 using a stereoselective Yb(OTf)3-promoted hetero Diels−Alder reaction ofthe derived imine 34 with Danishefsky's diene, affording adduct 35. Conjugate reduction andstereoselective equatorial ketone reduction of vinylogous amide 35 provided tricyclic intermediate36, which could then be elaborated in a few steps to stable hydroxyenone 53 via α-selenophenylenoneintermediate 52. The D-ring was then constructed, again using an intramolecular Wadsworth−Horner−Emmons olefination reaction to give phyllanthine (2).
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