title: Isorhizochalin: a minor unprecedented bipolar sphingolipid of stereodivergent biogenesis from the Rhizochalina incrustata.
abstract: Isorhizochalin (1) was isolated as its peracetate from the EtOH extract of the sponge Rhizochalina incrustata. Its structure and absolute stereochemistry were elucidated as (2S,3R,26R,27R)-2,27-diamino-3-O-beta-D: -galactopyranosyl-oxy-26-hydroxyoctacosan-18-one by extensive NMR, MS studies, chemical transformations, including micromolar-scale Baeyer-Villiger oxidation, and by analysis of CD spectra of isorhizochalinin perbenzoate (2b). Isorhizochalin is an unprecedented C-2 epimer of rhizochalin having an erythro configuration at the glycosylated 2-amino-3-alkanol alpha-terminus in contrast with a canonical threo configuration for other representatives of this structural group. Probable biogenesis of 1 is discussed in the context of known sphingolipid biosynthesis beginning with condensation of alanine with a fatty acyl CoA thioester. The aglycone, isorhizochalinin (2a), shows cytotoxicity against human leukemia HL-60 and THP-1 cells with IC(50) values of 2.90 and 2.20 microM, respectively.
authors.affiliation: Laboratory of MaNaPro Chemistry, Pacific Institute of Bioorganic Chemistry of the Russian Academy of Sciences, 690022 Vladivostok, Russia. makarieva@piboc.dvo.ru
authors.forename: Tatyana N
authors.initials: TN
authors.lastname: Makarieva
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Zakharenko
authors.forename: Pavel S
authors.initials: PS
authors.lastname: Dmitrenok
authors.forename: Alla G
authors.initials: AG
authors.lastname: Guzii
authors.forename: Vladimir A
authors.initials: VA
authors.lastname: Denisenko
authors.forename: Alexandra S
authors.initials: AS
authors.lastname: Savina
authors.forename: Doralyn S
authors.initials: DS
authors.lastname: Dalisay
authors.forename: Tadeusz F
authors.initials: TF
authors.lastname: Molinski
authors.forename: Valentin A
authors.initials: VA
authors.lastname: Stonik
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002942:Circular Dichroism; D005233:Fatty Alcohols / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D005697:Galactosides / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D018922:HL-60 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D011161:Porifera / Q000737:chemistry*; D013107:Sphingolipids / Q000737:chemistry* / Q000494:pharmacology; D013237:Stereoisomerism
chemical_list: D000970:Antineoplastic Agents; D005233:Fatty Alcohols; D005697:Galactosides; D013107:Sphingolipids; C548307:isorhizochalin; C548308:isorhizochalinin