An improved synthesis of α,β-unsaturated nitrones relevant to the stephacidins and analogs thereof

Bioorganic and Medicinal Chemistry Letters

Volumn 19, Issue 14, 2009, Pages 3808-3810

  Hafensteiner, Benjamin D ^a   Escribano, María ^a   Petricci, Elena ^a   Baran, Phil S ^a  

^a SCRIPPS RESEARCH INSTITUTE   (United States)

Author keywords

Click chemistry; Methodology; Oxidations; Synthesis

Indexed keywords

ALKALOID; ALPHA,BETA UNSATURATED NITRONE DERIVATIVE; AVRAINVILLAMIDE DERIVATIVE; NATURAL PRODUCT; NITRONE DERIVATIVE; STEPHACIDIN A; STEPHACIDIN B; STEPHACIDIN DERIVATIVE; UNCLASSIFIED DRUG;

ARTICLE; NONHUMAN; PRENYLATION; REACTION OPTIMIZATION; SYNTHESIS;

ANTINEOPLASTIC AGENTS; INDOLE ALKALOIDS; INDOLES; NITROGEN OXIDES; OXIDATION-REDUCTION;

EID: 67649641698     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2009.04.045     Document Type: Article

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25. 4, filtered and the solvent was removed under vacuum. The indoline derivative obtained was used directly in the next step.General procedure for the synthesis of N-hydroxy derivatives: indoline (1 equiv) was dissolved in a 1:1 mixture of MeOH/AcOEt (the solvent combination was used to insure complete dissolution of indoline). After the solution was coaled to -40 °C, dimethyldioxirane was added (1.1 equiv) and the reaction mixture was stirred at -40 °C for 1 h. Dimethylsulfide was added until its odor persisted and the reaction mixture was evaporated under high vacuum. The crude mixture was used directly in the next step.General procedure for the synthesis of nitrone derivatives: N-hydroxy derivative (1 equiv) was dissolved in THF (0.01 M) and chloranil (2 equiv) was added. The resulting yellow solution was sealed with a plastic cap and heated in an oil bath preheated to 70 °C. After 40 min the reaction was removed from the heat and the solvent was removed under vacuum. The residue was purified by column chromatography.
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