Callyspongiolide, a Cytotoxic Macrolide from the Marine Sponge Callyspongia sp.

Abstract

A novel macrolide, callyspongiolide, whose structure was determined by comprehensive analysis of the NMR and HRMS spectra, was isolated from the marine sponge Callyspongia sp. collected in Indonesia. The compound features a carbamate-substituted 14-membered macrocyclic lactone ring with a conjugated structurally unprecedented diene-ynic side chain terminating at a brominated benzene ring. Callyspongiolide showed strong cytotoxicity against human Jurkat J16 T and Ramos B lymphocytes.

Enantioselective total synthesis and structural assignment of callyspongiolide

“…However, the specific rotation of our HPLC purified (>98% purity) synthetic callyspongiolide ( R )- 2 {${false[\alpha false]}_{\mathrm{D}}^{\mathbf{20}}$ = −25.5 ( c 0.1, MeOH)} displayed the same sign and similar magnitude to the reported value {${false[\alpha false]}_{\mathrm{D}}^{\mathbf{20}}$ = −12.5 ( c 0.1, MeOH)}. 12 On the other hand, callyspongiolide ( S )- 2 showed a value significantly larger in magnitude {${false[\alpha false]}_{\mathrm{D}}^{\mathbf{20}}$ = −182 ( c 0.1, MeOH)}.…”

“…Of specific note, both synthetic callyspongiolide enantiomers have shown comparable magnitude of rotation which is higher than the reported values. 12,14 We therefore, assigned the absolute configuration and the C-21 stereocenter of the natural callyspongiolide same as the synthetic callyspongiolide ( R )- 2 .…”

“…7–11 Proksch and co-workers recently reported the isolation of callyspongiolide ( 1 , Figure 1) off the coast of Indonesia from the sponge, Callyspongia species. 12 Preliminary biological studies revealed that callyspongiolide displayed complete inhibition of the murine lymphoma cell line, L5178Y. It exhibited potent cytotoxicity against human Jurkat J16 T and Ramos B lymphocytes with IC 50 values of 70 nM and 60 nM, respectively.…”

Synthesis and Molecular Editing of Callyspongiolide, Part 1: The Alkyne Metathesis/trans‐Reduction Strategy

“…Bioassay‐guided fractionation of the methanol extract of a sponge of the Callyspongia genus collected off the Indonesian coast line led to the isolation of callyspongiolide (4.6 mg, 0.00092 % wet weight) . This captivating macrolide endowed with a highly unusual dienyne side chain exhibits remarkable cytotoxicity against human Jurkat J16 T and Ramos B lymphocytes with IC 50 values of 70 and 60 n m , respectively.…”

Enantioselective Synthesis of Both Epimers at C-21 in the Proposed Structure of Cytotoxic Macrolide Callyspongiolide

“…1 H (500 MHz) and 13 C NMR (125 MHz) spectra of both ( S )- 1 and ( R )- 1 epimers are virtually indistinguishable from the spectra reported for the natural product. 6 Further unambiguous assignment was difficult by 800 MHz 1 H NMR. Both specific rotations of our HPLC-purified 22 synthetic callyspongiolide epimers, however, showed opposite sign of rotation as well as larger magnitude; synthetic ( S )- 1 , ${\left[\alpha \right]}_{\mathrm{D}}^{20}+24.5$ ( c 0.1, MeOH); synthetic ( R )- 1 , ${\left[\alpha \right]}_{\mathrm{D}}^{20}+159$ ( c 0.1, MeOH) compared to that reported for the natural product, ${\left[\alpha \right]}_{\mathrm{D}}^{20}-12.5$ ( c 0.1, MeOH).…”