Towards stereochemical control: A short formal enantioselective total synthesis of pumiliotoxins 251D and 237A

Abstract

SummaryA concise enantioselective synthesis of the advanced intermediate 5 for the synthesis of pumiliotoxins (Gallagher’s intermediate) is described. The synthesis started from the regio- and trans-diastereoselective (dr = 98:2) reductive 3-butenylation of (R)-3-(tert-butyldimethylsilyloxy)glutarimide 14. After O-desilylation and Dess–Martin oxidation, the resulting keto-lactam 10 was subjected to a highly trans-stereoselective addition of the methylmagnesium iodide to give carbinol 11 as sole diastereomer. An efficient ring closure procedure consisting of ozonolysis and reductive dehydroxylation provided the indolizidine derivative 5, which completed the formal enantioselective total synthesis of pumiliotoxins 251D and 237A.

Towards Reaction Control: An Expeditious Access to Racemic 5‐Substituted Tetramates and 5‐Substituted Tetramic Acids from Malimides

“…In summary, we have demonstrated that by judicious selection of reaction conditions, the reactions of hemiaminals 2 are controllable [19] to give either tetramates 6 or tetramic acids 7, both in one-step. We thus developed a two-step divergent method for the syntheses of racemic 5-alkyltetramates (6) and 5-alkyltetramic acids (7) starting from malimide building blocks 1.…”

Synthesis of the Precursors of Pumiliotoxin 251D and Awajanomycin and Related Studies

“…4 The allylic bromides were hydrolyzed to give the alcohols 4 with retention of configuration. 5 (+)-Pumiliotoxin 251D was isolated from the frogs (Dendrobates pumilio) in South America, 6 and some total syntheses 7,8 and many formal syntheses [9][10][11][12][13][14][15][16] have been reported. 5 (+)-Pumiliotoxin 251D was isolated from the frogs (Dendrobates pumilio) in South America, 6 and some total syntheses 7,8 and many formal syntheses [9][10][11][12][13][14][15][16] have been reported.…”