Isorhizochalin: a minor unprecedented bipolar sphingolipid of stereodivergent biogenesis from the Rhizochalina incrustata.
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.
Makarieva
Tatyana N
TN
Laboratory of MaNaPro Chemistry, Pacific Institute of Bioorganic Chemistry of the Russian Academy of Sciences, 690022 Vladivostok, Russia. makarieva@piboc.dvo.ru
Zakharenko
Alexander M
AM
Dmitrenok
Pavel S
PS
Guzii
Alla G
AG
Denisenko
Vladimir A
VA
Savina
Alexandra S
AS
Dalisay
Doralyn S
DS
Molinski
Tadeusz F
TF
Stonik
Valentin A
VA
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
D000970:Antineoplastic Agents; D005233:Fatty Alcohols; D005697:Galactosides; D013107:Sphingolipids; C548307:isorhizochalin; C548308:isorhizochalinin