The synthesis of (+)-allopumiliotoxin 323B'.
This paper describes the synthesis of (+)-allopumiliotoxin 323B' (1) using the intramolecular [3 + 2]-cycloaddition reaction of the (Z)-N-alkenylnitrone 4. This synthesis began with (R)-tert-butyl-3-hydroxy-pent-4-enoate [(R)-13] which was obtained by enzymatic resolution with Amano PS lipase. A series of manipulations gave intermediate 17 and in situ coupling with 4-benzoyloxybutanal lead to the (Z)-N-alkenylnitrone 4 which underwent an intramolecular [3 + 2]-cycloaddition reaction to give the isoxazolidine 3 as the major cycloadduct. Isoxazolidine 3 provided the piperidinone 24 which upon diastereofacial selective addition of MeMgBr gave the required tertiary alcohol 25. Formation of the indolizidine core 2 was achieved by an intramolecular S(N)2 reaction. The side chain was assembled from a Wittig reaction between the phosphorane 8 and the enantiomerically pure aldehyde 9. Further modifications afforded the aldehyde 7 which underwent an aldol condensation with the potassium enolate of the indolizidone core 2. Dehydration gave the enone 37 which was converted into the anti-diol 38 by intramolecular hydride reduction. Finally, deprotection of the BOM protecting group gave (+)-allopumiliotoxin 323B' (1).
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Department of Chemistry, University of Cambridge, UK. abh1@cus.cam.ac.uk
Holmes
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D000470:Alkaloids / Q000138:chemical synthesis*; D000475:Alkenes; D000664:Amphibian Venoms; D000818:Animals; D007212:Indolizines; D015394:Molecular Structure; D010880:Piperidines; D011898:Ranidae; D013237:Stereoisomerism
D000470:Alkaloids; D000475:Alkenes; D000664:Amphibian Venoms; D007212:Indolizines; D010880:Piperidines; C438804:allopumiliotoxin 323B'; C035482:pumiliotoxin A