8-Isocyanoamphilecta-11(20),15-diene, a new antimalarial isonitrile diterpene from the sponge Ciocalapata sp.

Abstract

A new isonitrile diterpene of the amphilectane family, 8-isocyanoamphilecta-11(20),15-diene (4), was isolated from the sponge Ciocalapata sp., along with three known isonitriles, 8,15-diisocyano-11(20)-amphilectene (1), 7-isocyanoamphilecta-11(20),15-diene (2), and 8-isocyanoamphilecta-11(20),14-diene (3), and two steroidal peroxides, ergosterol peroxide (5) and 5α,9α-epidioxy-8α,14α-epoxy-(22E)-ergosta-6,22-dien-3β-ol (6). The structure of the new isonitrile was elucidated spectroscopically. In addition, anomalous multiplicities in the NMR spectra of some isolated isonitriles were observed and are reported here. The four isonitriles were strongly active against Plasmodium falciparum K1 with IC50 in a range of 0.09–1.07 μmol/L. Except for 1, which was cytotoxic against both MCF-7 and fibroblast cell lines, the other three diterpenes showed no significant cytotoxicity against either targeted cell lines. On the other hand, the steroidal peroxides 5 and 6, which were less active in the antimalarial bioassay (IC50 values of 6.28 and 7.13 µmol/L, respectively), were strongly cytotoxic against MCF-7 (IC50 values of 0.025 and 0.003 µmol/L, respectively), with very little toxicity against human fibroblasts.

Oxysterols from Free Radical Chain Oxidation of 7-Dehydrocholesterol: Product and Mechanistic Studies

“…We suggest that many of these natural oxysterols may be formed by a free radical chain oxidation of the corresponding Δ 5,7 -sterol by essentially the same mechanisms proposed in Schemes 3-5 for 7-DHC peroxidation. Specifically, ergosterol analogues of compounds 2a , 2b , 3 , 6a , 6b , 8 , 10 , 12a , and 12b have been isolated from fungal species,88-96 and analogues of compounds 3 , 6a , 8 , 10 , 12a , and 12b have been isolated from marine sponges 97-104. Other reported natural products that can be generated from the free radical oxidation process are analogues of compounds 22 , 23 , 24 , 34 , 35 , 36 , 37 , 38 , and 39 .…”

Syntheses and biological studies of marine terpenoids derived from inorganic cyanide

“…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.…”

Two Rare-Class Tricyclic Diterpenes with Antitubercular Activity from the Caribbean Sponge Svenzea flava. Application of Vibrational Circular Dichroism Spectroscopy for Determining Absolute Configuration

“…Contrary to previous reports on the geometry of the formamide group, the coupling constants of 7-NHC H O (δ 8.26, d, J = 12.3 Hz for the major rotamer 4a , and δ 8.04, d, J = 2.1 Hz for the minor 4b rotamer) clearly indicated the transoid conformation to be the dominant species. 3b,4 As the NMR data of 2 – 4 were virtually identical for comparable stereocenters, and the fact that the optical rotation of 4 ([α] D +44.0) was of similar magnitude and sign to those of 2 and 3 , it is likely that these three molecules all have identical absolute configuration. Furthermore, hydrolysis of isocyanide 2 with 98% AcOH yielded 4 in 65% yield demonstrating conclusively that the latter compound is in fact (1(14)- E ,3 S *,4 R *,7 S *,8 S *,11 R *,12 S *,13 R *)-7-formamidoisoneoamphilecta-1(14),15-diene.…”