Bifunctionalized Amphilectane Diterpenes from the Sponge Stylissa cf. massa

Abstract

Two new amphilectane-type diterpenes, 8-isocyanato-15-formamidoamphilect-11(20)-ene (1) and 8-isothiocyanato-15-formamidoamphilect-11(20)-ene (2), along with two known derivatives, 8-isocyano-15-formamidoamphilect-11(20)-ene (3) and 7-formamidoamphilect-11(20),15-diene (4), were isolated from the sponge Stylissa cf. massa. Diterpenes bearing two different isonitrile-related functionalities, as in 1-3, are rare. The coexistence of these compounds, all of which possess the identical carbon skeleton, in the same sponge specimen suggests interconversion among them. All the isolated compounds were tested for antimalarial activity. Compound 3 proved approximately 10 times more active than 1 and 2, indicating the importance of the isonitrile moiety to antimalarial activity versus the isocyanate and isothiocyanate groups, respectively. Compound 4, which contains only the formamide group, was inactive at the highest concentration tested.

Syntheses and biological studies of marine terpenoids derived from inorganic cyanide

“…clvii In total, 9 reports have ascribed varying levels of anti-malarial activity–from weak to single-digit nanomolar–for isonitrile containing natural products and synthetic variants, clearly establishing the ICTs as intriguing antimalarial lead structures. xxx,cxliii,clviii,clix,clx,clxi,clxii , A promising aspect of this collection of data is that several independent studies observed essentially equipotent activity between common chloroquine-sensitive (including D6 and HB3) and drug-resistant/ drug-insensitive (including W2 and Dd2) strains of P. falciparum parasites.…”

“…xxvi The variety of amphilectane structures has also grown, as shown in Figure 4B. xx,xxvii,xxviii,xxix,xxx Of particular interest are the methylamine and formamide, 77–78 , variants of the isoneoamphilectane scaffold, which were obtained from a Svenzea flava sponge and shown to display moderate antitubercular activity (MICs between 6 and 32 µg/mL against a M. tuberculosis H 37 RV). xxxi Also quite notable was a significant reassignment effort of the absolute and relative stereochemistry of several previously assigned xxxii compounds through a combination of X-ray and Mosher ester analysis.…”

Marine natural products

“…), 705 a potent antimalarial, has been achieved, 706 while the isolation of two new formamido-amphilectane diterpenes 829 and 830 from a Thai Stylissa massa (Koh-Tao, Surat-Thani Province) have been reported. 707 Jaspiferin A 831 was isolated from Jaspis stellifera (Guangdong, South China Sea) along with an oxidative degradation product jaspiferin B 832. 708 Chromodorolide D 833, a heavily rearranged spongian diterpene, was reported along with 834 from an unidentied sponge (Cape Manza, Okinawa).…”

Marine Isonitriles and Their Related Compounds

“…Examination of the sponge Stylissa cf. massa, collected also in Koh-Tao (Thailand) by Chanthathamrongsiri in 2012 revealed two C-5 derivatives of Amp2 , 8-isocyanato-15-formamidoamphilect-11(20)-ene ( Amp8 ) and 8-isothiocyanato-15-formamidoamphilect-11(20)-ene ( Amp9 ) [ 123 ].…”

“…In agreement with these findings are the results of Chanthathamrongsiri et al who proved the C-8 isonitrile Amp2 to have a tenfold higher antiplasmodial activity than the isocyanate ( Amp8 ) and the isothiocyanate Amp9 . The C-7-formamide Amp17 was inactive [ 123 ].…”