Isorhizochalin: a Minor Unprecedented Bipolar Sphingolipid of Stereodivergent Biogenesis from the Rhizochalina incrustata
- 127 Downloads
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-β-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 α-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 IC50 values of 2.90 and 2.20 μM, respectively.
KeywordsSphingolipids Two-headed sphingolipid HPLC NMR HRESI Absolute configuration CD Marine sponge Rhizochalina incrustata Cytotoxity
High performance liquid chromatography
High resolution mass spectrometry electrospray ionisation
Matrix assisted laser desorption/ionization time-of-flight
Nuclear magnetic resonance
Heteronuclear multiple bond correlation
- THP-1, HL-60
This investigation was supported by the Fogarty International Center and NIH (TWOO6301-01) and the NIH (AI039987 and CA122256 to T.F.M).The research described here was made possible in part by Program of Presidium of RAS “Molecular and Cell Biology”, Grant N SS-2813.2008.4 from the President of RF., Grant 09-04-00015-a from RFBR, and Grant 09-III-A-139 from FEB RAS.
- 3.Makarieva TN, Dmitrenok PS, Zakharenko AM, Denisenko VA, Guzii AG, Li R, Skepper CK, Molinski TF, Stonik VA (2007) Rhizochalins C and D from the sponge Rhizochalina incrustata. A rare threo-sphingolipid and a facile method for determination of the carbonyl position in α, ω-bifunctionalized ketosphingolipids. J Nat Prod 70:1991–1998CrossRefPubMedGoogle Scholar
- 12.Jin JO, Shastina VV, Park JI, Han JY, Makarieva TN, Fedorov SN, Rasskazov VA, Stonik VA, Kwak JY (2009) Differential induction of apoptosis of leukemic cells by rhizochalin two headed sphingolipids from sponge and its derivatives. Biol Pharm Bull 32:956–962Google Scholar
- 13.Tsukamoto S, Takeuchi T, Rotinsulu H, Mangindaan REP, Van Soest RWM, Ukai K, Kobayashi H, Namikoshi M, Ohta T, Yokosawa H (2008) Leucettamol A: a new inhibitor of Ubc13–Uev1A interaction isolated from a marine sponge, Leucetta aff. microrhaphis. Bioorg Med Chem Lett 18:6319–6320CrossRefPubMedGoogle Scholar
- 15.Baltrop JA, Owen TC, Cory AH, Cory JG (1991) 5-(3-Carboxymethoxyphenyl)-2-(4,5-dimethylthiazolyl)-3-(4-sulfophenyl) tetrazolium, inner salt (MTS) and related analogs of 3-(4,5-dimethylthiazolyl)-2,5-diphenyltetrazolium bromide (MTT) reducing to purple water-soluble formazans as cell-viability indicators. Bioorg Med Chem Lett 1:611–614CrossRefGoogle Scholar
- 16.Makarieva TN, Denisenko VA, Svetashev VI, Vysotsky MV, Stonik VA (1989) Cerebrosides from the Far-Eastern sponge Hymenyacidon assimilis. Chem Nat Comp 634–638 (in Russian)Google Scholar