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Solid-phase Synthesis of [4.4] Spirocyclic Oximes
Published on: February 6, 2019
Silylpyrrole Oxidation En Route to Saxitoxin Congeners Including 11-Saxitoxinethanoic Acid
Doris T Y Tang1, Jeffrey E Merit1, T Aaron Bedell1
1Department of Chemistry, Stanford University, 333 Campus Dr., Stanford, California 94305, United States.
Abstract:
Saxitoxin (STX) is the archetype of a large family (>50) of architecturally distinct, bisguanidinium natural products. Among this collection of isolates, two members, 11-saxitoxinethanoic acid (11-SEA) and zetekitoxin AB (ZTX), are unique, bearing carbon substitution at C11. A desire to efficiently access these compounds has motivated the development of new tactical approaches to a late-stage C11-ketone intermediate 26, designed to enable C-C bond formation using any one of a number of possible reaction technologies. Highlights of the synthesis of 26 include a metal-free, silylpyrrole oxidative dearomatization reaction and a vinylsilane epoxidation-rearrangement cascade to generate the requisite ketone. Nucleophilic addition to 26 makes possible the preparation of unnatural C11-substituted STXs. Olefination of this ketone is also demonstrated and, when followed by a redox-neutral isomerization reaction, affords 11-SEA.
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