Cembranoids studies

NT341 Arndt, R., J. E. Berg, and I. Wahlberg. Tobacco chemistry. Structure determi nation and biomimetic studies of five new tobacco cembranoids. Acta Chem Scand 1990 44(8) 814-825. 

Eight new cembranoids from tobacco-structural elucidation and conformational studies. Tetrahedron 1993 49(22) 4975-4992. 

Metabolism studies are essential for approval of any clinically useful drug. Microorganisms have been successfully used as in vitro models for prediction of mammalian drug metabolism due to the significant similarity of certain microbial enzyme systems, specifically fungi, with mammalian liver enzyme systems.66 The following metabolism study represents the first for a cembranoid diterpene and may aid future development of other cembranoids as clinically useful drugs. 

Sarcophytols A (46) and B (47) are simple cembranoids isolated from the Okinawan soft coral S. glaucum and have been reported to possess potent inhibitory activities against various classes of tumor promoters.70 71 Sarcophytol A (46) mediated dose-dependent diminution of 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced transformation of JB6 cells.72 When evaluated for potential to inhibit TPA-induced JB6 cell transformation, several of the sarcophine metabolites (48 to 58) mediated inhibitory responses greater than sarcophytol A (46) or sarcophine (45), most notably 7a-hydroxy-y8(19) deepoxysarcophine (50), which was comparable to 13-cz s-retinoic acid. These studies provide a basis for further development of novel furanocembranoids as anticancer agents. 

In the synthetic studies on cembranoid natural products by Marshall et al. [155], an alcohol-halide coupUng was used to construct the macrocycles. As shown in Scheme 87, the linear precursor 259 was cyclized to 260 in 71 /o yield by addition of 1 equiv of EtMgBr to a solution of the chloro alcohol 259 in HMPA-THF and stirring at reflux for 4 h. There are also other examples of this macrocyclization method [156]. 

PROGRESS OF STUDIES ON THE NATURAL CEMBRANOIDS FROM THE SOFT CORAL SPECIES OF SARCOPHYTON GENUS... 

Chemical examination of Sarcophyton glaucum collected at Ishigaki island, Okinawa Prefecture, resulted in the isolation of seven cembranoid diterpenes, namely sarcophytol A (3), sarcophytol A acetate (4), sarcophytol B (5), sarcophy-tonin A (6), and minor constituents sarcophytol C (7), D (8), and E (9). These compounds were found to be susceptible to autooxidation while being purified. The structural determination of these compounds was made mainly based on proton and carbon nuclear magnetic resonance (NMR) spectral evidence and degradative studies by ozonolysis. X-ray crystallographic analysis for the two crystalline compounds, sarcophytol B (5) and D (8), has been reported. The total lipid extracts of S. glaucum comprise about 40% sarcophytol A (3), 5% each of sarcophytol A acetate (4) and sarcophytonin A (6), about 1% sarcophytol B (5), and minor amounts of sarcophytol C (7), D (8), and E (9). 

Tobacco leaf has a complicated chemical composition including a variety of polymers and small molecules. The small molecules from tobacco belong to numerous classes of compounds such as hydrocarbons, terpenes, alcohols, phenols, acids, aldehydes, ketones, quinones, esters, nitriles, sulfur compounds, carbohydrates, amino acids, alkaloids, sterols, isoprenoids [48], Amadori compounds, etc. Some of these compounds were studied by pyrolysis techniques. One example of pyrolytic study is that of cuticular wax of tobacco leaf (green and aged), which was studied by Py-GC/MS [49]. By pyrolysis, some portion of cuticular wax may remain undecomposed. The undecomposed waxes consist of eicosyl tetradecanoate, docosyl octadecanoate, etc. The molecules detected in the wax pyrolysates include hydrocarbons (Cz to C34 with a maximum of occurrence of iso-Czi, normal C31 and anti-iso-C32), alcohols (docosanol, eicosanol), acids (hexadecanoic, hexadecenoic, octadecanoic, etc ). The cuticular wax also contains terpenoids such as a- and p-8,13-duvatriene-1,3-diols. By pyrolysis, some of these compounds are not decomposed and others generate closely related products such as seco-cembranoids (5-isopropyl-8,12-dimethyl-3E,8E,12E,14-pentadecatrien-2-one, 3,7,13-trimethyl-10-isopropyl-2,6,11,13-tetradecatrien-1al) and manols. By pyrolysis, c/s-abienol, (12-Z)- -12,14-dien-8a-ol, generates mainly frans-neo-abienol. 

Bowden, B.F., J.C. Coll, and S.J. Mitchell Studies of Australian Soft Corals. XVIII. Further Cembranoid Diterpenes from Soft Corals of the Genus Sarcophyton. Aust. J. Chem. 33, 879 (1980). 

Sanduja, R., Linz, G.S., Alam, M., Weinheimer, A.J., Martin, G.E., and Ezell, E.L. (1986a) 2D-NMR studies of marine natural products. IV. Isolation of the cembranoid diterpene jeunidn from the mollusc Plamxis sulcatus assignment of the H and NMR./. Heterocycl. Chem., 23, 529-535. 

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