New Nitrogenous Bisabolene-Type Sesquiterpenes from a Formosan Sponge <i>Axinyssa</i> sp.

Abstract

Key words sponge; Axinyssa sp.; bisabolene-type; cytotoxicity Studies in the chemistry of marine natural products, the marine sponges have emerged as one of the most prolific sources for discovery of novel secondary metabolites.1) Previous chemical investigations on sponges of the genus Axinyssa (order Halichondrida, family Halichondriidae) have led to the isolation and identification of various sesquiterpenes containing unusual nitrogenous functional groups as an isocyano, isothiocyanate, thiocyanate, bisabolene and formamide group.2-15) Some of these N-containing compounds have been found to possess several kinds of biological activities, such as antithelmintic, 2) antimicrobial, 4) antimalarial, 6) antifouling, 11) cytotoxic activities 12) and lethality for brine shrimp. 10) Our investigation of the chemical constituents of a sponge Axinyssa sp. yielded two new nitrogenous bisabolene-type sesquiterpenes, axinysalines A (1) and B (2), along with three known sesquiterpenes. The structures of 1 and 2 were established by detailed spectroscopic analysis and comparison of their NMR data with those of known analogues. The known sesquiterpenes were readily identified as 3-isocyanotheonellin (3), 16) 3-isocyano-7,8-epoxy-α-bisabolane (4) 7) and 3-formamidotheonellin (5), 17) by comparison of their spectral data with those reported in the literature. The cytotoxicity of metabolites 1-5 against the six cancer cell lines, human erythromyeloblastoid leukemia (K562), human T lymphoblast, acute lymphoblastic leukemia (Molt 4), human colon adenocarcinoma (HCT-116 and DLD-1), and human breast carcinoma (MDA-MB-231 and T47D) was studied.Compound 1, named axinysaline A, was isolated as an optically active, colorless oil. The molecular formula was determined to be C 21 H 35 NO 3 by high resolution-electrospray ionization (HR-ESI)-MS (m/z 372.2515, C 21 H 35 NO 3 Na) and NMR data, which corresponded to five degrees of unsaturation. The IR spectrum of 1 showed absorption bands at 3375, 1679 and 1746 cm −1 , suggesting the presence of an amide CO group and an ester CO group, which were supported by 13 C-NMR chemical shifts at δ 171.9 and 169.2 ppm, respectively. The 13 C-NMR and distortionless enhancement by polarization transfer (DEPT) spectral data of 1 showed the presence of 21 carbons (Table 1): seven methyls, four sp 3 methylenes, two sp 3 methines, three sp 2 methines, and two sp 3 quaternary carbons. The remaining three signals appearing in the lower field region of the spectrum are due to the quaternary carbons of one olefinic carbon (δ 140.2), one amide carbonyl and one ester carbonyl. From the 1 H-NMR spectrum of 1, the resonances of three olefinic protons (δ H 6.22, dd, J=14.5, 11.0 Hz; 5.81, d, J=11.0 Hz; 5.59 dd, J=15.5,7.0 Hz) were observed. Moreover, analysis of the 1

Marine Isonitriles and Their Related Compounds

“…[ 87 ]. Recently, axinysaline A ( Bi20 ) and axinysaline B ( Bi19 ) were found in an unidentified Formosan sponge of the genus Axinyssa by Liu et al [ 88 ].…”

Halichonic Acid B, a Rearranged Nitrogenous Bisabolene-Type Sesquiterpene from a Marine Sponge <i>Axinyssa</i> sp.

“…Sesquiterpenes with amine and isocyanate substituents were isolated from marine sponges Halichondria sp. 1) and Ciocalypta sp., 2) and other nitrogenous sesquiterpenes with formamide, [3][4][5] isonitrile, 6) isothiocyanate, 5,7) and urea 7) have been isolated from marine sponges of the genus Axinyssa. Recently, we also isolated a new rearranged nitrogenous bisabolene-type sesquiterpene, halichonic acid (2), with a novel 3-azabicyclo [3.3.1] nonene skeleton from Halichondria sp.…”

Halichonic acid, a new rearranged bisabolene-type sesquiterpene from a marine sponge Halichondria sp.

“…These bisabolene derivatives contain unique nitrogenous functional groups, such as an isothiocyanate, isonitrile, and formamide either at C-3 or C-7 of the bisabolene frameworks. They exhibit a broad range of biological activities including cytotoxicity [6,8], antimicrobial activity [6], and antifouling activity [13]. The biosynthetic pathways of these nitrogenous sesquiterpenes have attracted much attention, and incorporation experiments indicated that the precursor of the isonitrile group was either inorganic cyanide [14,15] or amino acids associated with the metabolism of tetrahydrofolate [16].…”