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Enantioselective Total Syntheses of Allopumiliotoxins 267A, 323B‘, and 339A. Application of Iodide-Promoted Iminium Ion−Alkyne Cyclizations for Forming Allopumiliotoxin A Alkaloids

1996; American Chemical Society; Volume: 118; Issue: 38 Linguagem: Inglês

10.1021/ja961640y

1943-2984

Christian Caderas, Renee M. Lett, Larry E. Overman, Michael H. Rabinowitz, Leslie A. Robinson, Matthew J. Sharp, Jeffery A. Zablocki,

Chemical synthesis and alkaloids

A concise, stereocontrolled strategy for the total synthesis of allopumiliotoxin A alkaloids is described. A much improved second generation total synthesis of enantiopure (+)-allopumiliotoxin 267A (3) was accomplished in 10 steps and 11% overall yield from the commercially available oxazolidinone precursor of alcohol 32 and 17 steps and 4% overall yield from N-[(benzyloxy)carbonyl]-l-proline. The first synthesis of (+)-allopumiliotoxin 323B' (4) rigorously confirms the complete stereostructure of 4 and establishes that the major C(15) epimer isolated from dendrobatid frogs has the 15S configuration. The total synthesis of 4 was realized in 5 steps and 17% overall yield from alkyne 39 and aldehyde 20; the synthesis proceeded in 13 steps and 6% overall yield from (S)-2-methyl-1-penten-3-ol and 17 steps and 3.5% overall yield from N-[(benzyloxy)carbonyl]-l-proline, the precursors, respectively, of alkyne 39 and pyrrolidine aldehyde 20. The first total synthesis of allopumiliotoxin 339A (5) also confirmed the full stereostructure of this alkaloid. The synthesis of enantiopure 5 was achieved in 5 steps and 32% overall yield from alkyne 45 and pyrrolidine aldehyde 20; the synthesis proceeded in 17 steps and ∼7% overall yield from N-[(benzyloxy)carbonyl]-l-proline and 16 steps and ∼6% overall yield from the commercially available oxazolidinone precursor of 45. These syntheses provide the best illustrations to date of the substantial utility of iodide-promoted iminium ion−alkyne cyclizations for constructing highly functionalized nitrogen heterocycles.