There is a growing interest in organic compounds containing the difluoromethyl group, as it is considered a lipophilic hydrogen bond donor that may act as a bioisostere of hydroxyl, thiol, or amine groups. A series of difluoromethyl anisoles and thioanisoles was prepared and their druglike properties, hydrogen bonding, and lipophilicity were studied. The hydrogen bond acidity parameters A (0.085-0.126) were determined using Abraham's solute H NMR analysis. It was found that the difluoromethyl group acts as a hydrogen bond donor on a scale similar to that of thiophenol, aniline, and amine groups but not as that of hydroxyl. Although difluoromethyl is considered a lipophilicity enhancing group, the range of the experimental Δlog P(water-octanol) values (log P(XCFH) - log P(XCH)) spanned from -0.1 to +0.4. For both parameters, a linear correlation was found between the measured values and Hammett σ constants. These results may aid in the rational design of drugs containing the difluoromethyl moiety.

The effects of the CF2H moiety on H-bond (HB) acidity and lipophilicity of various compounds, when attached directly to an aromatic ring or to other functions like alkyls, ethers/thioethers, or electron-withdrawing groups, are discussed. It was found that the CF2H group acts as a HB donor with a strong dependence on the attached functional group (A = 0.035–0.165). Regarding lipophilicity, the CF2H group may act as a more lipophilic bioisostere of OH but as a similar or less lipophilic bioisostere of SH and CH3, respectively, when attached to Ar or alkyl. In addition, the lipophilicity of ethers, sulfoxides, and sulfones is dramatically increased upon CH3/CF2H exchange at the α position. Interestingly, this exchange significantly affects not only the polarity and the volume of the solutes but also their HB-accepting ability, the main factors influencing log P oct. Accordingly, this study may be helpful in the rational design of drugs containing this moiety.

Ten new sesquiterpenes, nardosinanols A-I ( 1- 9) and lemnafricanol ( 10), have been isolated from several Kenyan soft corals, i.e., from Lemnalia sp., Paralemnalia clavata, Lemnalia africana, and Rhytisma fulvum fulvum. The structures and relative stereochemistry of these compounds were elucidated by interpretation of MS, COSY ( (1)H- (1)H correlations), HSQC, HMBC, and NOESY NMR spectroscopic experiments and in the case of 5 also by chemical transformation to compounds 11 and 12. Nine compounds ( 1- 9) are based on the nardosinane skeleton ( 1- 6 are nardosinanes and 7- 9 nornardosinanes). Lemnafricanol ( 10) possesses a novel tricyclic skeleton. Compounds 3, 7, and 10 were found to be toxic to brine shrimp with LC 50 values of 4.0, 0.35, and 0.32 microM, respectively.

A new sterol glycoside, auroside (1) and two new hydroxylated sterols, patusterol A and B (2, 3) have been isolated from the South African soft coral Eleutherobia aurea and from the Kenyan soft coral Lobophytum patulum. The structure elucidation was achieved from extensive 1D-and 2D-NMR and MS data, and in the case of auroside also by chemical reactions. In addition, from Lobophytum patulum, was also isolated a known nitrogen containing compound (Z)-N-[2-(4hydroxyphenyl)ethyl]-3-methyldodec-2-enamide, and from Eleutherobia aurea several, earlier reported, diterpenoids. Compound 2 was found to be toxic to brine shrimp embryos with an LC 50 value of 2.30 μM.