1,2-Dihydrochromeno[2,3-c]pyrrol-3-one Derivatives: Synthesis and HPLC-ECD Analysis

László Tóth; Attila Kiss-Szikszai; Gábor Vasvári; Ferenc Fenyvesi; Miklós Vecsernyés; Péter Mátyus; Sándor Antus; Attila Mándi; Tibor Kurtán

doi:10.1055/s-0037-1612085

Synlett, Inhaltsverzeichnis

Synlett 2019; 30(07): 799-802
DOI: 10.1055/s-0037-1612085

letter

1,2-Dihydrochromeno[2,3-c]pyrrol-3-one Derivatives: Synthesis and HPLC-ECD Analysis

László Tóth

^aDepartment of Organic Chemistry, University of Debrecen, P. O. Box 400, 4002 Debrecen, Hungary eMail: mandi.attila@science.unideb.hu eMail: kurtan.tibor@science.unideb.hu

^bDepartment of Organic Chemistry, Semmelweis University, Budapest Hungary

,

Attila Kiss-Szikszai

^aDepartment of Organic Chemistry, University of Debrecen, P. O. Box 400, 4002 Debrecen, Hungary eMail: mandi.attila@science.unideb.hu eMail: kurtan.tibor@science.unideb.hu

,

Gábor Vasvári

^cDepartment of Pharmaceutical Technology, University of Debrecen, Nagyerdei krt. 98., P. O. Box 78, 4010 Debrecen, Hungary

,

Ferenc Fenyvesi

^cDepartment of Pharmaceutical Technology, University of Debrecen, Nagyerdei krt. 98., P. O. Box 78, 4010 Debrecen, Hungary

,

Miklós Vecsernyés

^cDepartment of Pharmaceutical Technology, University of Debrecen, Nagyerdei krt. 98., P. O. Box 78, 4010 Debrecen, Hungary

,

Péter Mátyus

^dInstitute of Digital Health Sciences, Semmelweis University, Budapest, Hungary

,

Sándor Antus

^aDepartment of Organic Chemistry, University of Debrecen, P. O. Box 400, 4002 Debrecen, Hungary eMail: mandi.attila@science.unideb.hu eMail: kurtan.tibor@science.unideb.hu

^bDepartment of Organic Chemistry, Semmelweis University, Budapest Hungary

,

Attila Mándi *

^aDepartment of Organic Chemistry, University of Debrecen, P. O. Box 400, 4002 Debrecen, Hungary eMail: mandi.attila@science.unideb.hu eMail: kurtan.tibor@science.unideb.hu

,

Tibor Kurtán *

^aDepartment of Organic Chemistry, University of Debrecen, P. O. Box 400, 4002 Debrecen, Hungary eMail: mandi.attila@science.unideb.hu eMail: kurtan.tibor@science.unideb.hu

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Abstract

Alle Artikel dieser Rubrik

Published as part of the Special Section 10th EuCheMS Organic Division Young Investigator Workshop

Abstract

Ethyl-3-formyl-6-methoxy-(2H)-chromene-2-carboxylate was transformed to N-substituted 1,2-dihydrochromeno[2,3-c]pyrrol-3-ones in a domino reductive amination–lactamization reaction. Isomerization of the double bond and the inherently labile stereogenic center was studied, and HPLC-ECD analysis of a chiral 1,2-dihydrochromeno[2,3-c]pyrrol-3(3aH)-one derivative aided by TDDFT-ECD calculation allowed configurational assignment of the separated enantiomers. Antiproliferative activity of the products was demonstrated on the CaCo-2 human epithelial colorectal adenocarcinoma cell line.

Key words

1,2-dihydrochromeno[2,3-c]pyrrol-3-one - isomerization - HPLC-ECD - TDDFT-ECD - antiproliferative

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Referenzen

References and Notes
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16 General Procedure for the Synthesis of rac-17a,b,e,f,j and rac-19c,d,g–jTo a stirred solution of 13 (0.100 g, 0.38 mmol) in ethanol (10 mL), primary amine 14a–j (1.3 equiv, 0.49 mmol) was added, and the reaction mixture was heated to reflux for 3 h. After cooling to room temperature, the ethanol was removed under reduced pressure. The residue was dissolved in methanol, NaBH₄ (2 equiv, 0.029 g, 0.76 mmol) was added, the reaction mixture was stirred for 10 min and then concentrated under reduced pressure. Water (10 mL) and dichloromethane (10 mL) were added, and the organic layer was separated. The aqueous phase was extracted with dichloromethane (2 × 10 mL), the combined organic layers were washed with saturated aq. NaHCO₃, dried over MgSO₄, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel.
17 (±)-2-Pentyl -7-methoxy-1,2-dihydrochromeno[2,3-c]pyrrol-3(3aH)-one (17e)The residue was purified by column chromatography on silica gel (hexane/ethyl acetate, 2:1) to give the product as a white solid (65 mg, 56%); mp 174–175 °C. ¹H NMR (400 MHz, CDCl₃): δ = 0.90 (t, J = 14.4 and 7.2 Hz, 5′-H, 3 H), 1.32 (m, 3′-H and 4′-H, 4 H), 1.59 (m, 2′-H, 2 H), 3.41 (m, 1′-H, 2 H), 3.76 (s, OMe, 3 H), 4.12 (m, 1-H, 2 H), 5.12 (s, 3a-H, 1 H), 6.40 (s, 9-H, 1 H), 6.62 (d, J = 2.8 Hz, 8-H, 1 H), 6.71 (m, 6-H, 1 H), 6.99 (d, J = 8.8 Hz, 5-H, 1 H). ¹³C-NMR (100 MHz, CDCl₃): δ = 13.9 (C-5′), 22.4 (C-4′), 26.7 (C-3′), 28.9 (C-2′), 42.7 (C-1′), 47.9 (C-1), 55.7 (OMe), 74.3 (C-3a), 112.2 (C-8), 114.3 (C-5), 117.4 (C-6), 119.1 (C-9), 123.6 (C-9a), 127.8 (C-8a), 154.7 (C-7), 168.4 (C-3). IR (KBr): ν = 1032, 1243, 1490, 1693, 2954 cm^–1. GC–MS: 287.1.
18 (±)-2-Hexyl-7-methoxy-1,2-dihydrochromeno[2,3-c]pyrrol-3(3aH)-one (17f)The residue was purified by column chromatography on silica gel (hexane/ethyl acetate, 3:1) to give the product as a white solid (42 mg, 36%); mp 157–159 °C. ¹H NMR (400 MHz, CDCl₃): δ = 0.87 (m, 6′-H, 3 H), 1.31 (m, 3′-H, 4′-H, 5′-H, 6 H), 1.56 (m, 2′-H, 2 H), 3.40 (m, 1′-H, 2 H), 4.12 (s, OMe, 3 H), 4.13 (m, 1-H, 2 H), 5.12 (s, 3a-H, 1 H), 6.40 (s, 9-H, 1 H), 6.62 (d, J = 2.8 Hz, 8-H, 1 H), 6.71 (m, 6-H, 1 H), 6.99 (d, J = 8.8 Hz, 5-H, 1 H). ¹³C-NMR (100 MHz, CDCl₃): δ = 13.9 (C-6′), 22.4 (C-5′), 26.3 (C-3′), 26.9 (C-2′), 31.3 (C-4′), 42.6 (C-1′), 47.7 (C-1), 55.6 (OMe), 74.1 (C-3a), 112.1 (C-8), 114.2 (C-5), 117.2 (C-6), 118.9 (C-9), 123.4 (C-9a), 127.7 (C-8a), 146.4 (C-4a), 154.6 (C-7), 168.2 (C-3). IR (KBr): ν = 1032, 1243, 1489, 1693, 2954 cm^–1. GC–MS: 301.1.
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