Search for new compounds and biologically active substances from Chinese marine organisms*

In search of new pharmaceutically valuable substances from marine organisms, we have been engaged in chemical studies on the constituents of corals, sponges and algae collected in the South China Sea. This paper summarizes some of our research results. Terpenes, nitrogen-containing compounds and polyhydroxylated sterols are mainly discussed. The corals, marine sponges and algae are abundant natural resources in the South China Sea. Due to unusual environment as compared with terrestrial organisms, marine organisms produce a variety of substances having various unprecedented chemical structures and exhibiting signi®cant biological activities. In search of new pharmaceutically valuable substances from marine organisms, we have been engaged in chemical studies on the constituents of some 50 species of corals, marine sponges and algae collected in the South China Sea and have found more than 120 new compounds. Many of these exhibited signi®cant biological activities. In this paper, terpenoids, nitrogen-containing compounds and polyhydroxylated sterols are mainly discussed. Some 50 new terpenoids have been obtained. The most interesting terpenoids are methyl sartortuoate (1) and methyl isosartortuoate (2). 1 and 2 are tetraterpenes with unique biscembrenoid skeleton. Their structures were determined by spectroscopic methods and X-ray diffraction analysis. Both 1 and 2 exhibited moderate cytotoxicity against P-388 and KB cells. Structurally, compounds 1 and 2 are likely to be formed biogenetically by two cembrenoids via Diels±Alder reaction. We have suggested a biosynthetic path way for these compounds [1,2]. Stelletin A (3) was isolated from the sponge Stelletta tenuis Linduren (Scheme 1). HRMS m/z 463.2874 (M‡ 1) revealed the molecular formula C30H38O4. The UV spectrum revealed an extended conjugated system like of isomalabaricane-type triterpene (3A). Comparison of the H NMR data of 3 and * Invited Lecture presented at the 21st IUPAC International Symposium on The Chemistry of Natural Products (ISCNP-21), Beijing, China, 11±16 October 1998, pp. 1024±1166. 2Corresponding author. Scheme 1 3A revealed the two sets of data to be nearly identical except that the signal for H-28 of 3 was observed at lower ®eld (d62.35 instead of d2.07) and that of H-15 was observed at higher ®eld (d6.99 instead of d8.26). This indicated that H-28 was deshielded by the C-12 keto group in 3 and so must be cisto it while H-15 is transto ketone. Thus structure 3 was assigned to this new triterpene (3). 3 is strongly toxic toward P388 leukemia cells (ED50ˆ 1 ́ 10 mg/mL) [3]. Nineteen new sesterterpenes with bishomosealarane skeleton have been isolated from marine sponge Phyllosponggia folliascens [4±6]. Their structures have been determined by elucidation of the spectral data. In comparison to scalarane-type sesterterpenes, an ethyl group at C-4 formed an additional chiral center. The observation of NOE between proton (pro-S) (d1.53 ppm) and 21-CH3 protons (d0.96 ppm) of phyllofenone A (4) indicated the b-orientation for ethyl group. A difference NOE technique was helpful for this purpose. Upon saturation the 21-CH3 (s, 0.68 ppm) clearly showed NOE with the pro-S H-20. The features were identical with that obtained in a 2D J-resolved spectrum. Hence a b-orientation is assioned to the ethyl group [4]. No absolute con®guration of any compound of this class was assigned de®nitely before. We have ®rst established the absolute con®guration of this class by using modi®ed Mosher's method. Phyllactone B (6), which has a secondary hydroxyl group at C-16, was taken as an example for this purpose. Thus (R)and (S)-MTPA esters of phyllactone B (6) were prepared., proton signals of the corresponding derivatives were assigned by 2D-COSY spectra, respectively. The Dd(ds±dR) for protons on the E ring were negative, whereas those observed for protons on the B and C rings have positive values. Thus the absolute con®guration at C-16 was con®rmed as R, and all other chiral centers in this molecule were assigned as 4S, 12R, 24S [5]. Phyllofenone A (4) shows anti-fungal activity against Candida pseudotropicalls [4]. Phyllofenone B (5) [6] showed potent cytotoxicity toward P388 cell line (IC50ˆ 5 mg/mL). Pathylactone A (10) is a rare norsequiterpene with a g-spirolactone moiety. Its absolute stereochemistry was assigned by CD method [7]. Compound (9) exhibited anti-fungal activity [8]. Compounds (7) and (8) showed potent cytotoxic toward P388 cell lines. The rare sesquiterpene lactam, clavulinin (11), was obtained from the soft coral Clavularia in ̄ata. The molecular formula of 11 was established as C16H22NO4 on the basis of FABMS, C NMR and DEPT. The existence of one hydroxyl group, two carbonyl groups and three kinds of carbon±carbon double bonds, i.e. CH2ˆCH±, CH2ˆCR and CˆC, were deduced by IR and NMR spectral data. The signals of protons and carbons of the molecule were assigned and connected by H-H COSY, H-C COSY, 1148 L. ZENG et al. q 1999 IUPAC, Pure Appl. Chem. 71, 1147±1151 Scheme 2