Enantioselective [4 + 1] Annulation Reactions of α‑Substituted Ammonium Ylides To Construct Spirocyclic Oxindoles

Ammonium ylides have a long history in organic synthesis, but their application in asymmetric catalysis is still underdeveloped in regard to both substrate scope and reaction pathways compared with phosphorus and sulfur ylides. Here a previously unreported asymmetric [4 + 1] annulation reaction of 3-bromooxindoles and electron-deficient 1-azadienes has been developed through ammonium ylide catalysis of a newly designed 2′-methyl α-isocupreine (α-MeIC), efficiently delivering spirocyclic oxindole compounds incorporating a dihydropyrrole motif in excellent enantioselectivity (up to 99% ee). To the best of our knowledge, this work represents the first example of asymmetric catalysis of ammonium ylides bearing α-substitutions, and the catalytic [4 + 1] annulation pathway of ammonium ylides is also unprecedented. Moreover, ¹H NMR, mass spectroscopy, and computational calculation studies were conducted, and the catalytic cycle and a tentative explanation of the enantioselective mechanism have been successfully elucidated

Enantioselective [4 + 1] Annulation Reactions of α‑Substituted Ammonium Ylides To Construct Spirocyclic Oxindoles

Ammonium ylides have a long history in organic synthesis, but their application in asymmetric catalysis is still underdeveloped in regard to both substrate scope and reaction pathways compared with phosphorus and sulfur ylides. Here a previously unreported asymmetric [4 + 1] annulation reaction of 3-bromooxindoles and electron-deficient 1-azadienes has been developed through ammonium ylide catalysis of a newly designed 2′-methyl α-isocupreine (α-MeIC), efficiently delivering spirocyclic oxindole compounds incorporating a dihydropyrrole motif in excellent enantioselectivity (up to 99% ee). To the best of our knowledge, this work represents the first example of asymmetric catalysis of ammonium ylides bearing α-substitutions, and the catalytic [4 + 1] annulation pathway of ammonium ylides is also unprecedented. Moreover, ¹H NMR, mass spectroscopy, and computational calculation studies were conducted, and the catalytic cycle and a tentative explanation of the enantioselective mechanism have been successfully elucidated

Bioassay- and Chemistry-Guided Isolation of Scalemic Caged Prenylxanthones from the Leaves of <i>Garcinia bracteata</i>

With bioassay- and chemistry-guided fractionation, seven new caged prenylxanthones including two scalemic mixtures, epiisobractatin (<b>1</b>), 13-hydroxyisobractatin (<b>2</b>), 13-hydroxyepiisobractatin (<b>3</b>), 8-methoxy-8,8a-dihydrobractatin (<b>4</b>), 8-ethoxy-8,8a-dihydrobractatin (<b>5</b>), garcibracteatone (<b>6</b>), and 8-methoxy-8,8a-dihydroneobractiatin (<b>7</b>), and the eight known compounds <b>8</b>–<b>15</b> were isolated from the leaves of <i>Garcinia bracteata</i>. The structures were unambiguously elucidated through analysis of spectroscopic data. The 2D structures and relative configurations of <b>1</b> and <b>5</b> were confirmed by X-ray crystallographic analysis. The separation of the enantiomers of <b>1</b>–<b>5</b> was accomplished by chiral-phase HPLC. The absolute configurations of the enantiomers of <b>1</b> and <b>5</b> were assigned by comparison of the experimental and calculated electronic circular dichroism (ECD) spectra. The absolute configurations of the related compounds were determined via comparisons of their ECD data with those of the enantiomers of <b>1</b> and <b>5</b>, respectively. Notably, compound <b>7</b>, with a neo caged skeleton, is the first representative of a novel type of caged xanthone lacking a Δ^8(8a) double bond. The isolated compounds exhibited significant cell growth inhibitory activities in vitro against human leukemic HL-60 and K562 cell lines, with GI₅₀ values ranging from 0.2 to 8.8 μM. A preliminary structure–activity relationship is discussed

Bioassay- and Chemistry-Guided Isolation of Scalemic Caged Prenylxanthones from the Leaves of <i>Garcinia bracteata</i>

With bioassay- and chemistry-guided fractionation, seven new caged prenylxanthones including two scalemic mixtures, epiisobractatin (<b>1</b>), 13-hydroxyisobractatin (<b>2</b>), 13-hydroxyepiisobractatin (<b>3</b>), 8-methoxy-8,8a-dihydrobractatin (<b>4</b>), 8-ethoxy-8,8a-dihydrobractatin (<b>5</b>), garcibracteatone (<b>6</b>), and 8-methoxy-8,8a-dihydroneobractiatin (<b>7</b>), and the eight known compounds <b>8</b>–<b>15</b> were isolated from the leaves of <i>Garcinia bracteata</i>. The structures were unambiguously elucidated through analysis of spectroscopic data. The 2D structures and relative configurations of <b>1</b> and <b>5</b> were confirmed by X-ray crystallographic analysis. The separation of the enantiomers of <b>1</b>–<b>5</b> was accomplished by chiral-phase HPLC. The absolute configurations of the enantiomers of <b>1</b> and <b>5</b> were assigned by comparison of the experimental and calculated electronic circular dichroism (ECD) spectra. The absolute configurations of the related compounds were determined via comparisons of their ECD data with those of the enantiomers of <b>1</b> and <b>5</b>, respectively. Notably, compound <b>7</b>, with a neo caged skeleton, is the first representative of a novel type of caged xanthone lacking a Δ^8(8a) double bond. The isolated compounds exhibited significant cell growth inhibitory activities in vitro against human leukemic HL-60 and K562 cell lines, with GI₅₀ values ranging from 0.2 to 8.8 μM. A preliminary structure–activity relationship is discussed

Bioassay- and Chemistry-Guided Isolation of Scalemic Caged Prenylxanthones from the Leaves of <i>Garcinia bracteata</i>

With bioassay- and chemistry-guided fractionation, seven new caged prenylxanthones including two scalemic mixtures, epiisobractatin (<b>1</b>), 13-hydroxyisobractatin (<b>2</b>), 13-hydroxyepiisobractatin (<b>3</b>), 8-methoxy-8,8a-dihydrobractatin (<b>4</b>), 8-ethoxy-8,8a-dihydrobractatin (<b>5</b>), garcibracteatone (<b>6</b>), and 8-methoxy-8,8a-dihydroneobractiatin (<b>7</b>), and the eight known compounds <b>8</b>–<b>15</b> were isolated from the leaves of <i>Garcinia bracteata</i>. The structures were unambiguously elucidated through analysis of spectroscopic data. The 2D structures and relative configurations of <b>1</b> and <b>5</b> were confirmed by X-ray crystallographic analysis. The separation of the enantiomers of <b>1</b>–<b>5</b> was accomplished by chiral-phase HPLC. The absolute configurations of the enantiomers of <b>1</b> and <b>5</b> were assigned by comparison of the experimental and calculated electronic circular dichroism (ECD) spectra. The absolute configurations of the related compounds were determined via comparisons of their ECD data with those of the enantiomers of <b>1</b> and <b>5</b>, respectively. Notably, compound <b>7</b>, with a neo caged skeleton, is the first representative of a novel type of caged xanthone lacking a Δ^8(8a) double bond. The isolated compounds exhibited significant cell growth inhibitory activities in vitro against human leukemic HL-60 and K562 cell lines, with GI₅₀ values ranging from 0.2 to 8.8 μM. A preliminary structure–activity relationship is discussed