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ate cytotoxic action against several animal and human tumor cell lines, could be envisioned as functionalized structural congeners of eupalmerin acetate (I) and eupalmerin (2), two well-known y-cembranolides isolated earlier from specimens of the gorgonian collected near Puerto Rican waters (21-24). The specimens of E. mammosa were collected off the West coast of Puerto Rico near Mona Island and were frozen after collection and then freeze-dried prior to extraction with 1:l MeOH-EtOAc. From the hexane and CHC1, extracts, diterpenes 3-15 were isolated by conventional chromatographic procedures (see Experimental). Results and discussionThe composition C22H3206 for the new terpenoid uprolide-A acetate (3) derives from high-resolution fabms and I3c nmr ~CEMBRANOUDE SKELETON HO OAcH OAc H data. The latter, obtained in CDCI,, revealed 22 resonances for 4 CH,, 6 CH2, 7 CH, and 5 C. Three of the seven methine carbons were sp3 at a heteroatom, two were sp3 not connected to a heteroatom, and two were olefinic. One of the methylene carbons was sp2 and two of the quaternary carbon atoms were those of ester C=O functionalities. This suggests a tricyclic diterpene all three cycles of which are accounted for by an epoxidized cembranolide, as in the case of eupalmerin acetate (1). Uprolide-A acetate (3) shows an ultraviolet absorption maximum at 2 12 nm (E 25 300) suggesting the existence of an a-methylene-y-butyrolactone ring. The infrared spectrum inferred the presence of a hydroxyl(3550 cm-'), a conjugated carbonyl(1766 cm-I), and isolated ester (1733 cm-') moieties. The 'H nmr spectrum (300 MHz; CDC1,) shows the signals of four olefinic protons (6 6.10 (lH, d, J = 3.3 Hz), 5.45 (lH, d, J = 15.6 Hz), 5.39 (lH, m), and 5.29 (lH, d, J = 3.3 Hz)), the presence of three 3H singlets at 6 1.89, 1.35, and 1.27 indicating an acetate ester group and methyl groups in an E-trisubstituted epoxide and tertiary carbinol, respectively, while a 3H doublet at 6 0.85 ( J = 6.9 Hz) indicated a methyl group bonded to a tertiary carbon atom. In addition, the 'H nmr spectrum shows three separate methine protons on carbon atoms bearing oxygenat65.11 (lH,d,J= 10.2Hz),4.80(1H,d,J=8.1Hz), and 2.93 (lH, dd, J = 3.6, 10.2 Hz). The proton networks were determined by H-H COSY and decoupling difference spectra, and the connectivity of each network through the quaternary carbons was deduced by INEPT and NOESY spectra, which led to the structure 3 for uprolide-A acetate. The E configuration of the h6 olefin was suspected from the high-field chemical shift value (6 73.7) of the allylic C-8 resonance line (25), the presence of a strong sharp infrared band at 968 cm-', the absence of nOe between the ethylenic protons H-6 and H-7, and the coupling constant observed for the partially overlapped doublet centered at 6 5.45 ( J = 15.6 Hz) ascribed to H-7. The

Taste evaluation is a crucial factor for determining acceptance of medicines by patients. The human taste panel test is the main method used to establish the overall palatability and acceptability of a drug product to a patient towards the end of development. Non-human in vitro and in vivo taste-evaluation tools are very useful for pre-formulation, quality control and screening of formulations. These non-human taste assessment tools can be used to evaluate all aspects of taste quality. The focus of this review is bitterness because it is a key aspect of taste in association with the development of medicines. In this review, recent in vitro (analytical) and in vivo (non-human) tools are described for the assessment of the bitter taste of medicines. Their correlations with human taste data are critically discussed. The potential for their use in early screening of the taste of active pharmaceutical ingredients (APIs) to expedite paediatric formulation development is also considered.

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