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.

Marine natural products

“…409 Rhizochalina incrustata (Madagascar) yielded the bipolar sphingolipid isorhizochalin 408. 410 The taurine derivative 2-palmitamidoethane sulfonic acid 409 was isolated from Haliclona sp. (Hainan Is., China).…”

Glycosides from Marine Sponges (Porifera, Demospongiae): Structures, Taxonomical Distribution, Biological Activities and Biological Roles

“…In this case, D-alanine should be employed as a precursor of 156 with retention of configuration at the C-2 and C-27 centers. Isolation of minor isorhizochalin ( 161 ) [86], an unprecedented epimer of 156 with erythro configuration at the glycosylated 2-amino-3-alkanol α-terminus and threo configuration on ω-terminus, suggest that α-terminus in this compound may be biosynthesized from L-alanine, while ω-terminus from D-alanine. D-Alanine may be originated from a host-derived epimerase or a symbiotic bacterium in the sponge (Chart 27) [86].…”

Secondary Metabolites from Marine Sponges of the Genus Oceanapia: Chemistry and Biological Activities

“…71 was a C-2 epimer of 60 with an erythro configuration at the glycosylated 2-amino-3-alkanol-αterminus, in contrast to the canonical threo configuration for other representatives of this structural group. In the bioassay, its aglycone, isorhizochalinin (72), showed cytotoxicity against human leukemia HL-60 and THP-1 cells with IC 50 values of 2.90 and 2.20 µM, respectively [38].…”