title: Total synthesis of pachastrissamine together with its 4-epi-congener via [3,3]-sigmatropic rearrangements and antiproliferative/cytotoxic evaluation.
abstract: Synthesis of the HCl salts of two anhydrophytosphingosines, jaspine B (1) and its 4-epi-congener 5 from easily available dimethyl l-tartrate and/or l-arabinose, is described. The key transformations are the efficient incorporation of a chiral amino group via [3,3]-sigmatropic rearrangements, a Wittig olefination for the instalment of the carbon backbone and the acid-promoted building-up of a tetrahydrofuran framework. Evaluation for in vitro antiproliferative/cytotoxic activity with a panel of human tumour cell lines using a MTT assay revealed for some compounds of our strategy noteworthy activity. Compound 1·HCl (IC50: 0. 41-2.35 μM), its antipode ent-1·HCl (IC50: 4.07-5.69 μM) and also stereoisomer 4·HCl (IC50: 4.28-6.10 μM) exhibited significant potency compared with clinically available anticancer drugs such as cisplatin (IC50: 11.4-14.7 μM) and etoposide (IC50: 1.2-21.2 μM) on MDA-MB-231, MCF-7 and Jurkat cells.
authors.affiliation: Department of Organic Chemistry, Institute of Chemical Sciences, Faculty of Science, P.J. Šafárik University, Moyzesova 11, 040 01 Košice, Slovak Republic. Electronic address: miroslava.martinkova@upjs.sk.
authors.forename: Miroslava
authors.initials: M
authors.lastname: Martinková
authors.affiliation: Department of Organic Chemistry, Institute of Chemical Sciences, Faculty of Science, P.J. Šafárik University, Moyzesova 11, 040 01 Košice, Slovak Republic.
authors.forename: Eva
authors.initials: E
authors.lastname: Mezeiová
authors.affiliation: Department of Organic Chemistry, Institute of Chemical Sciences, Faculty of Science, P.J. Šafárik University, Moyzesova 11, 040 01 Košice, Slovak Republic.
authors.forename: Milica
authors.initials: M
authors.lastname: Fabišíková
authors.affiliation: Department of Organic Chemistry, Institute of Chemical Sciences, Faculty of Science, P.J. Šafárik University, Moyzesova 11, 040 01 Košice, Slovak Republic.
authors.forename: Jozef
authors.initials: J
authors.lastname: Gonda
authors.affiliation: Department of Pharmacology, Faculty of Medicine, P.J. Šafárik University, SNP 1, 040 66 Košice, Slovak Republic.
authors.forename: Martina
authors.initials: M
authors.lastname: Pilátová
authors.affiliation: Department of Pharmacology, Faculty of Medicine, P.J. Šafárik University, SNP 1, 040 66 Košice, Slovak Republic.
authors.forename: Ján
authors.initials: J
authors.lastname: Mojžiš
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic; D006801:Humans; D023303:Oxazolidinones / Q000138:chemical synthesis / Q000737:chemistry; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism
chemical_list: D000970:Antineoplastic Agents; D023303:Oxazolidinones; C468594:pachastrissamine; D013110:Sphingosine
keywords: Anhydrophytosphingosines; Anticancer activity; Jaspine B; Pachastrissamine; Stereoselective synthesis; [3,3]-Heterosigmatropic rearrangements