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Lipids

, 44:1155 | Cite as

Isorhizochalin: a Minor Unprecedented Bipolar Sphingolipid of Stereodivergent Biogenesis from the Rhizochalina incrustata

  • Tatyana N. MakarievaEmail author
  • Alexander M. Zakharenko
  • Pavel S. Dmitrenok
  • Alla G. Guzii
  • Vladimir A. Denisenko
  • Alexandra S. Savina
  • Doralyn S. Dalisay
  • Tadeusz F. Molinski
  • Valentin A. Stonik
Communication

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-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.

Keywords

Sphingolipids Two-headed sphingolipid HPLC NMR HRESI Absolute configuration CD Marine sponge Rhizochalina incrustata Cytotoxity 

Abbreviations

HPLC

High performance liquid chromatography

HRMS-ESI

High resolution mass spectrometry electrospray ionisation

MALDI-TOF

Matrix assisted laser desorption/ionization time-of-flight

NMR

Nuclear magnetic resonance

COSY

Correlation spectroscopy

HMBC

Heteronuclear multiple bond correlation

CD

Circular dichroism

THP-1, HL-60

Cell lines

IC50

Inhibition concentration

TFA

Trifluoroacetic acid

Notes

Acknowledgments

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.

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Copyright information

© AOCS 2009

Authors and Affiliations

  • Tatyana N. Makarieva
    • 1
    Email author
  • Alexander M. Zakharenko
    • 1
  • Pavel S. Dmitrenok
    • 1
  • Alla G. Guzii
    • 1
  • Vladimir A. Denisenko
    • 1
  • Alexandra S. Savina
    • 1
  • Doralyn S. Dalisay
    • 2
  • Tadeusz F. Molinski
    • 2
  • Valentin A. Stonik
    • 1
  1. 1.Laboratory of MaNaPro ChemistryPacific Institute of Bioorganic Chemistry of the Russian Academy of SciencesVladivostokRussia
  2. 2.Department of Chemistry and Biochemistry, Skaggs School of Pharmacy and Pharmaceutical SciencesUniversity of CaliforniaSan DiegoUSA

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