Studies of the Deracemization of (±)‐2‐Hydroxy‐1‐tetralone by <i>Trichosporon cutaneum</i>

Lunardi, Inês; Cazetta, Tarcila; Conceição, Gelson José Andrade da; Moran, Paulo J. S.; Rodrigues, J. Augusto R.

doi:10.1002/adsc.200600331

Cited by 10 publications

(5 citation statements)

References 36 publications

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“…1 H NMR spectroscopic evidence confirmed a ( trans )-1,2-diol arrangement for all three cases. For example, coupling constants at δ 4.27, 4.28, and 4.48 ppm ( J = 5.85, 5.7, and 5.5 Hz) for H–C(1) in 24a – c , respectively, were found to correlate well with published data for 24a . The two hydroxy groups in 24a – c were protected using TBSCl and imidazole at room temperature to provide 25a – c in 59–83% yield.…”

Section: Chemistrysupporting

confidence: 67%

“…1 H NMR spectrum identical to published data. 33 (trans)-5-Bromo-1,2,3,4-tetrahydronaphthalene-1,2-diol (24b). As described above, 23b (3.57 g, 17.1 mmol) provided crude (trans)-4-bromo-1a,2,3,7b-tetrahydronaphtho[1,2-b]oxirene (10c, 4.47 g) as a colorless sticky oil in a first step with 68% purity (containing 25% m-chlorobenzoic acid).…”

Section: ■ Resultsmentioning

confidence: 99%

“…Benzylic oxidation at C(4) in (trans)-19 was achieved according to the mild method developed by Suresh et al 30 with published data for 24a. 33 The two hydroxy groups in 24a−c were protected using TBSCl and imidazole at room temperature to provide 25a−c in 59−83% yield. The benzylic methylene position at C(4) was oxidized to the respective α-tetralones 26a− c in 31−83% yield, again by means of the aforementioned mixture of oxidizing reagents NaClO 2 and t-BuOOH.…”

Section: ■ Resultsmentioning

confidence: 99%

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Verification of the Major Metabolic Oxidation Path for the Naphthoyl Group in Chemoattractant Receptor-Homologous Molecule Expressed on Th2 Cells (CRTh2) Antagonist 2-(2-(1-Naphthoyl)-8-fluoro-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)acetic Acid (Setipiprant/ACT-129968)

et al. 2015

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Various racemic and enantioenriched (trans)-X,Y-dihydroxy-X,Y-dihydronaphthoyl analogues as well as X-hydroxy-naphthoyl analogues of CRTh2 antagonist 2-(2-(1-naphthoyl)-8-fluoro-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)acetic acid (1, Setipiprant/ACT-129968) were synthesized in order to gain insight into regio- and enantioselectivity of the metabolic oxidation of 1 and to verify the structures of four metabolites that were proposed earlier in a clinical ADME study. Analytical data of the synthetic standards were compared with data from samples of biological origin. The two major metabolites M7 and M9 were unambiguously verified as 2-(2-((trans)-3,4-dihydroxy-3,4-dihydronaphthalene-1-carbonyl)- and 2-(2-((trans)-5,6-dihydroxy-5,6-dihydronaphthalene-1-carbonyl)-8-fluoro-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)acetic acid, respectively, each composed of two enantiomers with 68% and 44% ee in favor of (+)-(3S,4S)-M7 and (+)-(5S,6S)-M9, respectively. Likewise, minor metabolites M3 and M13 were identified as 2-(8-fluoro-2-(5-hydroxy-1-naphthoyl)- and 2-(8-fluoro-2-(4-hydroxy-1-naphthoyl)-1,2,3,4-tetrahydro-5H-pyrido[4,3-b]indol-5-yl)acetic acid, respectively.

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Section: Chemistrysupporting

confidence: 67%

Section: ■ Resultsmentioning

confidence: 99%

Section: ■ Resultsmentioning

confidence: 99%

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Verification of the Major Metabolic Oxidation Path for the Naphthoyl Group in Chemoattractant Receptor-Homologous Molecule Expressed on Th2 Cells (CRTh2) Antagonist 2-(2-(1-Naphthoyl)-8-fluoro-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)acetic Acid (Setipiprant/ACT-129968)

et al. 2015

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“…At 25 °C, the enantio‐enriched ( R )‐ 3 a was obtained in 15:85 e.r. whereas the one‐pot process only gave 33:67 e.r 9. When repeating this reaction with different concentrations, we found a significant impact on conversion.…”

Section: Methodsmentioning

confidence: 72%

Rhodium(I)‐Catalyzed Domino Asymmetric Ring Opening/Enantioselective Isomerization of Oxabicyclic Alkenes with Water

Tsui¹,

Lautens²

2012

Angew Chem Int Ed

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“…whereas the one-pot process only gave 33:67 e.r. [9] When repeating this reaction with different concentrations, we found a significant impact on conversion. At 0.1m concentration, only 12 % product was isolated (e.r.…”

mentioning

confidence: 84%

Rhodium(I)‐Catalyzed Domino Asymmetric Ring Opening/Enantioselective Isomerization of Oxabicyclic Alkenes with Water

Tsui

Lautens

2012

Angewandte Chemie

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Rhodium(I)-catalyzed asymmetric ring-opening (ARO) reaction of strained bicyclic alkenes has been demonstrated as a highly efficient and enantioselective process for generating a functionalized dihydronaphthalene core. [1] Our group has previously reported that chiral Rh I complexes catalyze ring opening of oxa-and azabicyclic alkenes with soft nucleophiles such as alcohols, phenols, thiols, amines, anilines, malonates and carboxylates in high yield and enantioselectivity. [2] The products are generated by an S N 2' nucleophilic displacement of the bridgehead leaving group with inversion to give the 1,2trans product as a single regio-and diastereomer. This method has been recently demonstrated as a viable strategy for synthesizing bioactive aminotetralins rotigotine and (S)-8-OH-DPAT. [3] Although various heteroatom nucleophiles have been employed in ARO, the use of water-the simplest nucleophile-has not been demonstrated. Based on previous studies, [2] water-induced ARO of oxabenzonorbornadiene 1 a should yield chiral trans-1,2-diol 2 a. Instead, we isolated the unexpected 2-hydroxy-1-tetralone product 3 a exclusively in the presence of catalytic [Rh(cod)Cl] 2 /(R,S)-PPF-PtBu 2 (cod = cyclooctadiene) in aqueous THF [4] (Scheme 1). Reaction at 25 8C afforded enantio-enriched 3 a (enantiomeric ratio, e.r. = 33:67), a higher reaction temperature (50 or 80 8C) caused a significant decrease in enantioselectivity. To the best of our knowledge, the formation of tetralone products such as 3 a is unprecedented in ARO reactions. We subsequently investigated the effects of ligand, catalyst loading, concentration, and reaction temperature (Table 1).No reaction took place without added ligand (entry 1). Reaction at 25 8C (0.2 m concentration) with 5 mol % [Rh-(cod)Cl] 2 and 10 mol % (R,S)-PPF-PtBu 2 gave tetralone product 3 a in 79 % yield (entry 2, cf. Scheme 1). As the catalyst loading was decreased to 2 mol %, we obtained a mixture of diol 2 a (major product) and tetralone 3 a (entry 3). Reaction concentration also had a significant effect on product distribution. Lower concentration (0.1m) favored diol formation whereas higher concetration (0.4 m) favored tetralone formation (entries 4 and 5). It was found that Scheme 1. Formation of 2-hydroxy-1-tetralone 3 a by Rh I -catalyzed ARO of oxabenzonorbornadiene 1 a with water. Table 1: Combined effects of ligand, catalyst loading, concentration, and reaction temperature. Entry Ligand Catalyst loading [c] T [8C] t [h] 2 a [%] 3 a [%] 4 a [%]

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Studies of the Deracemization of (±)‐2‐Hydroxy‐1‐tetralone by Trichosporon cutaneum

Cited by 10 publications

References 36 publications

Verification of the Major Metabolic Oxidation Path for the Naphthoyl Group in Chemoattractant Receptor-Homologous Molecule Expressed on Th2 Cells (CRTh2) Antagonist 2-(2-(1-Naphthoyl)-8-fluoro-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)acetic Acid (Setipiprant/ACT-129968)

Verification of the Major Metabolic Oxidation Path for the Naphthoyl Group in Chemoattractant Receptor-Homologous Molecule Expressed on Th2 Cells (CRTh2) Antagonist 2-(2-(1-Naphthoyl)-8-fluoro-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)acetic Acid (Setipiprant/ACT-129968)

Rhodium(I)‐Catalyzed Domino Asymmetric Ring Opening/Enantioselective Isomerization of Oxabicyclic Alkenes with Water

Rhodium(I)‐Catalyzed Domino Asymmetric Ring Opening/Enantioselective Isomerization of Oxabicyclic Alkenes with Water

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