Stereoselective Synthesis and Antiproliferative Activity of Steviol-Based Diterpene 1,3-Aminoalcohol Regioisomers
A series of novel diterpene-type 1,3-aminoalcohols and their regioisomers have been synthesised from natural stevioside in a stereoselective manner. The key intermediate β-keto alcohol was prepared using Wagner–Meerwein rearrangement of the epoxide derived from steviol methyl ester. The primary amin...
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MDPI AG
2023-12-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/28/24/7962 |
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| author | Dorottya Bai Zsuzsanna Schelz Mária Fanni Boncz István Zupkó Zsolt Szakonyi |
| author_facet | Dorottya Bai Zsuzsanna Schelz Mária Fanni Boncz István Zupkó Zsolt Szakonyi |
| author_sort | Dorottya Bai |
| collection | DOAJ |
| description | A series of novel diterpene-type 1,3-aminoalcohols and their regioisomers have been synthesised from natural stevioside in a stereoselective manner. The key intermediate β-keto alcohol was prepared using Wagner–Meerwein rearrangement of the epoxide derived from steviol methyl ester. The primary aminoalcohol was formed via Raney-nickel-catalysed hydrogenation of an oxime, and a versatile library of aminoalcohols was synthesised using a Schiff base with the primary amines. The aminoalcohol regioisomers were prepared from the mesylate of the β-keto alcohols. The corresponding primary aminoalcohol was formed via the palladium-catalysed hydrogenation of hydroxyl-azide, and click reactions of the latter were also carried out. The new compounds were characterised using 1D- and 2D-NMR techniques and HRMS measurements. The in vitro investigations showed high inhibition of cell growth in human cancer cell lines (HeLa, SiHa, A2780, MCF-7 and MDA-MB-231) in the case of naphthalic <i>N</i>-substituted derivatives. The antiproliferative effects were assayed using the MTT method. |
| first_indexed | 2024-03-08T20:29:58Z |
| format | Article |
| id | doaj.art-6a78e1330c9a4d4f8da727b2d2e509f3 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-08T20:29:58Z |
| publishDate | 2023-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-6a78e1330c9a4d4f8da727b2d2e509f32023-12-22T14:27:12ZengMDPI AGMolecules1420-30492023-12-012824796210.3390/molecules28247962Stereoselective Synthesis and Antiproliferative Activity of Steviol-Based Diterpene 1,3-Aminoalcohol RegioisomersDorottya Bai0Zsuzsanna Schelz1Mária Fanni Boncz2István Zupkó3Zsolt Szakonyi4Interdisciplinary Excellence Center, Institute of Pharmaceutical Chemistry, University of Szeged, Eötvös utca 6, H-6720 Szeged, HungaryInstitute of Pharmacodynamics and Biopharmacy, University of Szeged, Eötvös utca 6, H-6720 Szeged, HungaryInterdisciplinary Excellence Center, Institute of Pharmaceutical Chemistry, University of Szeged, Eötvös utca 6, H-6720 Szeged, HungaryInstitute of Pharmacodynamics and Biopharmacy, University of Szeged, Eötvös utca 6, H-6720 Szeged, HungaryInterdisciplinary Excellence Center, Institute of Pharmaceutical Chemistry, University of Szeged, Eötvös utca 6, H-6720 Szeged, HungaryA series of novel diterpene-type 1,3-aminoalcohols and their regioisomers have been synthesised from natural stevioside in a stereoselective manner. The key intermediate β-keto alcohol was prepared using Wagner–Meerwein rearrangement of the epoxide derived from steviol methyl ester. The primary aminoalcohol was formed via Raney-nickel-catalysed hydrogenation of an oxime, and a versatile library of aminoalcohols was synthesised using a Schiff base with the primary amines. The aminoalcohol regioisomers were prepared from the mesylate of the β-keto alcohols. The corresponding primary aminoalcohol was formed via the palladium-catalysed hydrogenation of hydroxyl-azide, and click reactions of the latter were also carried out. The new compounds were characterised using 1D- and 2D-NMR techniques and HRMS measurements. The in vitro investigations showed high inhibition of cell growth in human cancer cell lines (HeLa, SiHa, A2780, MCF-7 and MDA-MB-231) in the case of naphthalic <i>N</i>-substituted derivatives. The antiproliferative effects were assayed using the MTT method.https://www.mdpi.com/1420-3049/28/24/7962diterpenesteviolaminoalcoholstereoselectiveregioisomerantiproliferative activity |
| spellingShingle | Dorottya Bai Zsuzsanna Schelz Mária Fanni Boncz István Zupkó Zsolt Szakonyi Stereoselective Synthesis and Antiproliferative Activity of Steviol-Based Diterpene 1,3-Aminoalcohol Regioisomers Molecules diterpene steviol aminoalcohol stereoselective regioisomer antiproliferative activity |
| title | Stereoselective Synthesis and Antiproliferative Activity of Steviol-Based Diterpene 1,3-Aminoalcohol Regioisomers |
| title_full | Stereoselective Synthesis and Antiproliferative Activity of Steviol-Based Diterpene 1,3-Aminoalcohol Regioisomers |
| title_fullStr | Stereoselective Synthesis and Antiproliferative Activity of Steviol-Based Diterpene 1,3-Aminoalcohol Regioisomers |
| title_full_unstemmed | Stereoselective Synthesis and Antiproliferative Activity of Steviol-Based Diterpene 1,3-Aminoalcohol Regioisomers |
| title_short | Stereoselective Synthesis and Antiproliferative Activity of Steviol-Based Diterpene 1,3-Aminoalcohol Regioisomers |
| title_sort | stereoselective synthesis and antiproliferative activity of steviol based diterpene 1 3 aminoalcohol regioisomers |
| topic | diterpene steviol aminoalcohol stereoselective regioisomer antiproliferative activity |
| url | https://www.mdpi.com/1420-3049/28/24/7962 |
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