An efficient synthesis and cytotoxic profile of D-ribo-phytosphingosine and its analogues

0573972 - ÚACH 2024 RIV GB eng J - Článek v odborném periodiku
Želinská, M. - Vargová, K. - Pončáková, T. - Pilátová, M. B. - Martinková, M. - Majirská, M. - Kuchár, J. - Litecká, Miroslava - Prchal, L.
An efficient synthesis and cytotoxic profile of D-ribo-phytosphingosine and its analogues.
Tetrahedron. Roč. 143, AUG (2023), č. článku 133541. ISSN 0040-4020. E-ISSN 1464-5416
Institucionální podpora: RVO:61388980
Klíčová slova: D-ribo-phytosphingosine * Phytoceramides * [3,3]-sigmatropic rearrangements * OCM * Antiproliferative activity
Obor OECD: Inorganic and nuclear chemistry
Impakt faktor: 2.1, rok: 2022
Způsob publikování: Omezený přístup
https://doi.org/10.1016/j.tet.2023.133541

In this paper we describe the efficient synthesis of D-ribo-phytosphingosine and its analogues commencing from the easily available L-erythrose chiron, which already contained the future C-3 and C-4 stereocentres of our target compounds. Construction of the remaining C-2 stereochemistry relied on aza-Claisen rearrangements to establish the desired vicinal aminoalcohol motif. The aliphatic chain was introduced by means of an olefin cross metathesis process. Completion of this phytosphingolipid synthesis was then achieved through the suitable selection of functional group interconversions, accompanied by selective deprotection protocols. Preliminary in vitro experiments revealed higher antiproliferative activity of the unnatural D-arabino-phytosphingosine 3. HCl in comparison to cisplatin against three of the five cancer cell lines evaluated, with IC50 values ranging from 4.17 μM to 7.63 μM. Moreover, compound 3. HCl has better inhibitory effects on the proliferation of the aforementioned malignant cell lines than its natural stereochemical congener 2. HCl.
Trvalý link: https://hdl.handle.net/11104/0344353