Cembranoids, compounds with 14-membered macrocyclic skeleton, are known to exhibit a wide range of biological activities including anticancer properties.1) Since 1998, sarcophine (1), a cembranoid diterpene, has been investigated for its potential as a chemopreventive agent. 2)Bioconversion of (1) yielded several hydroxylated metabolites.2) These metabolites showed improved activity, compared not only to sarcophine, but also to sarcophytol A (2), which is a structurally related and well established chemopreventive cembranoid.2,3) Despite the promising results, there was one additional attempt toward optimizing the anticancer activity of sarcophine.4) This attempt involved semisynthetic transformation of sarcophine and its lactone opened derivative yielding potent hydroxylated derivatives. 4)The Red Sea soft coral Sarcophyton glaucum is a rich source of sarcophine with yields up to 3% of animal, dry weight.5) The high yield along with promising bioactivity makes sarcophine an ideal target for semisynthetic modifications. Hence our goal is to generate a structurally diverse library of sarcophine derivatives and test their biological activities. Previous reports involved generation of oxygenated and nitrogen containing sarcophine derivatives.2,4,6) Our first attempt towards semisynthetic modification involved oxymercuration-demercuration and halogenation of sarcophine. 7)This study targets the generation of sulfur-containing derivatives of sarcophine by targetting the epoxide ring. Sulfurcontaining functionalities are known to confer anticancer properties to several natural and synthetic products.8-10) For example, the anticancer potential of garlic is attributed to its organic sulfides including allicin.10) Sulfur-containing compounds are known to promote detoxification, which helps the liver to breakdown carcinogenic substances.11) The anticancer potential of sarcophine and its derivatives was evaluated by studying their effect on the highly malignant ϩSA mammary epithelial cell proliferation. Finally, the potential of NSAID's in reducing the risk of several malignancies prompted the investigatation of the effect of the chemopreventive sarcophine and its derivatives on the release of inflammatory mediators like thromboxane B 2 and superoxide anion in activated rat neonatal microglia. 12) Results and DiscussionReaction of 1 with ammonium thiocyanate in the presence of antimony trichloride yielded two sulfur and nitrogen-containing derivatives 3 and 4 in reasonable yields.The HR-MS spectrum 3 displayed a molecular ion peak [MϩH] ϩ at m/z 376.1940, suggesting the molecular formula C 21 H 29 NO 3 S, and eight degrees of unsaturation. The IR absorption band at 2159 cm Ϫ1 indicated the presence of a thio- Sarcophine (1), a cembranoid diterpene is known to inhibit the process of tumorigenesis. Sarcophine can be isolated in large amounts from the Red Sea soft coral Sarcophyton glaucum and hence is an ideal target for semisynthetic or biocatalytic modifications. Hydroxylated derivatives of 1 were reported to improve its...

Cembranoids are natural diterpenes with 14-membered macrocyclic rings. The simplest natural cembranoid, (+)-cembrene, was isolated from pine oleoresin. Sarcophytols A and B are known cembranoids that inhibit tumor promotion. Sarcophine is a related cembranoid isolated from the Red Sea soft coral Sarcophyton glaucum. Sarcophine and its bioconversion products and semisynthetic derivatives are reported to possess cancer chemopreventive activity. Oxymercuration-demercuration of sarcophine using Hg(OAc)2 and NaBH4 afforded four new rearranged and hydroxylated products. Bromination of sarcophine with N-bromosuccinimide (NBS) furnished two new brominated and rearranged products. Reaction with iodine gave the known iso-sarcophinone and (+)-sarcophytoxin B. Structure elucidation was based on a combination of transition state modeling, molecular dynamics, mechanistic considerations, and 2D NMR data. The antiproliferative activity of the new products is also reported.

The soft coral Sarcophyton glaucum is a rich resource of several bioactive cembranoids. Sarcophytol A (1) and sarcophine (2) are cembranoid diterpenes reported from this soft coral and extensively investigated for their cancer chemopreventive properties. This study aimed at investigating the antimetastatic potential of the major cembranoids, sarcophine (2) and 2-epi-16-deoxysarcophine (3), from the Red Sea soft coral S. glaucum. Biocatalytic transformation of 3 using Rhizopus stolonifer ATCC 6227a and Absidia spinosa ATCC 6648 afforded four new metabolites, 5-7 and 9, along with the known 9alpha-hydroxysarcophine (8). Sarcophine, 2-epi-16-deoxysarcophine, and metabolites 5-9 revealed significant antimetastatic activity against the highly metastatic mouse melanoma cell line (B16B15b). Cembranoids demonstrate a great potential for further development as antimetastatic agents.