Synthesis of Etrasimod (APD334): Al2O3-Promoted Decarboxylative Rearrangements of Cyclopentenones with Stereochemical Inversion DOI

J. Hsu,

TszIn Leung,

Yang‐Chang Wu

et al.

The Journal of Organic Chemistry, Journal Year: 2024, Volume and Issue: 89(17), P. 12524 - 12532

Published: Aug. 16, 2024

This study presents an efficient synthesis pathway for etrasimod, starting from (+)-cis-4-acetoxy-2-cyclopenten-1-ol, yielding 5.6% overall with 98% enantiomeric excess. The crucial intermediate, (4R)-anilinocyclopent-2-enone, was derived the (S)-alcohol/isocyanate adduct through a concerted, Al2O3-promoted decarboxylative rearrangement, which inverted configuration. A tetracyclic fused lactam formed via one-pot acylation-Michael addition, followed by keto α-arylation. Subsequent removal of oxo group facilitated cyclopenta[b]indol-3-ylacetic acid series reactions, including methanolysis, indoline oxidation, and hydrolysis.

Language: Английский

Stereoselective Access to Spiro-isoindolinone Scaffolds via Catalytic Asymmetric aza-Piancatelli Rearrangement DOI
Ling Yu, Yurong Tang,

Xukun Nie

et al.

Organic Letters, Journal Year: 2024, Volume and Issue: 26(36), P. 7667 - 7671

Published: Aug. 29, 2024

A chiral Brønsted acid catalyzed asymmetric aza-Piancatelli rearrangement of 3-furyl-3-hydroxyisoindolinones with anilines has been developed, enabling the divergent construction spiro-cyclopentenone-isoindolinones in high yields excellent diastereo- and enantioselectivities even under a low catalyst loading 0.5 mol%.

Language: Английский

Citations

2
Trivalent Phosphine-Catalyzed [4+1] Spiro-annulation Reaction Using Allenyl Imide and Methylene Cyclocompounds DOI

Zi-Qiu Zhang,

Zhenkai Zhang, Yuhao Wang

et al.

The Journal of Organic Chemistry, Journal Year: 2024, Volume and Issue: 89(9), P. 6607 - 6614

Published: April 16, 2024

The trivalent phosphine-catalyzed [4+1] spiro-annulation reaction of allenyl imide and activated methylene cyclocompounds has been developed for the construction various spiro-2-cyclopenten-1-ones. Oxindoles, 3-isochromanones, 2-indanones are selected as 1C synthons to capture in situ-generated bis-electrophilic α,β-unsaturated ketenyl phosphonium intermediate, affording corresponding monospiro- bispiro-cyclopentenones good excellent yields (≤91%) under mild conditions. primary attempt at asymmetric catalysis using monophosphine (R)-SITCP provides promising enantioselectivity (45% ee). A plausible mechanism is also proposed.

Language: Английский

Citations

1
Synthesis of Etrasimod (APD334): Al2O3-Promoted Decarboxylative Rearrangements of Cyclopentenones with Stereochemical Inversion DOI

J. Hsu,

TszIn Leung,

Yang‐Chang Wu

et al.

The Journal of Organic Chemistry, Journal Year: 2024, Volume and Issue: 89(17), P. 12524 - 12532

Published: Aug. 16, 2024

This study presents an efficient synthesis pathway for etrasimod, starting from (+)-cis-4-acetoxy-2-cyclopenten-1-ol, yielding 5.6% overall with 98% enantiomeric excess. The crucial intermediate, (4R)-anilinocyclopent-2-enone, was derived the (S)-alcohol/isocyanate adduct through a concerted, Al2O3-promoted decarboxylative rearrangement, which inverted configuration. A tetracyclic fused lactam formed via one-pot acylation-Michael addition, followed by keto α-arylation. Subsequent removal of oxo group facilitated cyclopenta[b]indol-3-ylacetic acid series reactions, including methanolysis, indoline oxidation, and hydrolysis.

Language: Английский

Citations

0