Novel Trinor-eremophilanes (Dendryphiellin B,C, and D), Eremophilanes (Dendryphiellin E,F, and G), and Branched C9-Carboxylic Acids (Dendryphiellic Acid A and B) from the Marine Deuteromycete Dendryphiella salina (SUTHERLAND) PUGHet NICOT

Further investigation of global extracts from cultures of the marine deuteromycete Dendryphiella salina leads to the isolation of three novel trinor-eremophilanes esterified by branched C₉-carboxylic acids, dendryphiellin B (= (+)-(1R*,2S*,7R*,8aR*)-1,2,6,7,8,8a-hexahydro-7-hydroxy-1,8a-dimethyl-6-oxonaphthalen-2-yl (6R*, 2E, 4E)-6-hydroxy-6-methylocta-2,4-dienoate; (+)- 2 ), dendryphiellin C (=(+)-(1R*, 2S*, 7R*, 8aR*)-1,2,6,7,8,8a-hexa-hydro-7-hydroxy-1,8a-dimethyl-6-oxonaphthalen-2-yl (6S, 2E, 4E)-6-methylocta-2,4-dienoate; (+)- 3 )), and dendryphiellin D (=(+)-(1R*, 2S*, 7R*, 8aR*)-1,2,6,7(8,8a-hexahydro-7-hydroxy-1,8a-dimethyl-6-oxonaphthalen-2-yl (6R*,2E,4E)-6-(hydroxymethyl)octa-2,4-dienoate; (+)- 4 ). An intact eremophilane, dendryphiellin E ( 5 ), and its ethanolysis product dendryphiellin F whose absolute configuration is represented by structural formula (+)- 6 are also isolated from the above extracts. Dendryphiellin E exists as an open form 5a in equilibrium with a closed form 5b . A similar equilibrium exists between the open form 8a and the closed form 8b of a non-esterified eremophilane, dendryphiellin G ( 8 ), which is isolated too from the above extracts and proves structurally related to the cyclic portion of 5 . Finally, the free, branched C₉-carboxylic acids dendryphiellic acid A ((+)- 9 ) and B ((+)- 10 ) which correspond to side chains of the above esterified terpenes are also isolated from the above extracts.     

Determination of retinoids in galenicals by column liquid chromatography with fluorescence and diode-array detection

Simple and rapid reversed-phase gradient column liquid chromatography (LC) with fluorescence detection at different wavelengths was developed for the simultaneous analysis of all-trans, 13-cis, 9-cis retinoic acids, vitamin A palmitate and beta-carotene in galenicals. The assay results agreed with those obtained by an LC method with diode-array UV detection. A post-column on-line photochemical reactor (irradiation at 254 and 366 nm) was inserted between the LC column and the fluorescence detector to enhance the performance of the method. Two fluorescence spectra (photoreactor on and off) were obtained for each analyte which proved useful for the unambiguous identification of the various analytes.     

The Active Centres of Agelastatin A,a Strongly Cytotoxic Alkaloid of the Coral Sea Axinellid Sponge Agelas dendromorpha,as Determined by Comparative Bioassays with Semisynthetic Derivatives

Agelastatin A ( 1 ), an unusual alkaloid of the axinellid sponge Agelas dendromorpha from the Coral Sea, can be selectively acetylated (→ 7 ) or methylated at OH? C(8a) (→ 4 ), peracetylated (→ 8 ) or permethylated at OH? C(8a), NH(5), and NH(6) (→ 5 ), or, finally, subjected to C(9)? C(8a) (→ 14 ) or C(5b)? C(8a) β-elimination (→ 11–13 ), in a regiospecific manner or not, depending on the reaction conditions. Under acidic conditions, compound 12 adds H₂O or MeOH, regioselectively though not endo/exo stereoselectively, giving transoid/cisoid mixtures 1/18 or 4/19 , respectively. Similarly 11 or 13 add MeOH to give mixtures (?)- 2/20 or 15/16 , respectively. Compound 13 also adds AcOH giving mixture 8/17 . The intermediate cisoid form obtained on treatment of 21 with H₃O⁺ undergoes N(5)? N(6) bridging affording pentacyclic 22 which constitutes a proof for the cisoid configuration. From conformational studies, rules are devised that allow assigning the configuration of these compounds from NMR data. In vitro comparative cytotoxicity assays of these compounds show that for high cytotoxic activity, such as of 1 in vivo, unsubstituted OH? C(8a), H? N(5), H? N(6) moieties are needed in the natural B/D transoid configuration.     

Caulerpenyne-Amine Reacting System as a Model for in vivo Interactions of Ecotoxicologically Relevant Sesquiterpenoids of the mediterranean-adapted tropical green seaweed caulerpa taxifolia

Caulerpenyne ( 1 ), the most abundant of the ecotoxicologically relevant sesquiterpenoids of the Mediterranean-adapted tropical green seaweed Caulerpa taxifolia, was found to react with Et₃N or pyridine in MeOH by initial deprotection of C(1)HO to give oxytoxin 1 ( 2a ), previously isolated from the sacoglossan mollusc Oxynoe olivacea. With BuNH₂, without any precaution to exclude light, 1 gave the series of racemic 3 and 4 , and achiral (4E,6E)- 5 , (4E,6Z)- 5 , (4Z,6E)- 5 , and (4Z,6Z)- 5 pyrrole compounds, corresponding to formal C(4) substitution, 4,5-β-elimination, and (E/Z)-isomerization at the C(4)?C(5) and C(6)?C(7) bonds. Changing to CDCl₃ as solvent in the dark, 1 gave cleanly, via 2a as an intermediate, 3 and (4E,6E)- 5 . The latter proved to be prone to (E/Z)-photoisomerization. Under standard acetylation conditions, 3 gave (4E,6E)- 5 via acetamide 7 as an intermediate. Particular notice is warranted by selective deprotection of 1 at C(1), mimicking enzyme reactions, and unprecedented formation of pyrrole compounds from freely-rotating, protected 1,4-dialdehyde systems.     

The chiral determinant and the eta invariant

For { _y },y, a one parameter family of invertible Weyl operators of possibly non-zero index acting on spinors over an even dimensional compact manifoldX, we express the phase of the chiral determinant det _– in terms of the invariant of a Dirac operator acting on spinors over ×X.Supported in part by NSF Grant No. PHY-82-15249Supported in part by NSF Grant PHY 8605978 and the Robert A. Welch Foundation     

Analytical problems related to the preparation of samples used in studies on metallobiochemistry of heavy metals pollution using neutron activation analysis

Severe analytical problems are associated with the analysis of heavy metals at very low levels in biological samples. This impose a high degree of sophistication of the NAA involving treatment of the sample before irradiation such as chemical separations, physical treatments and biochemical fractionation, the experimental evaluation of interfering nuclear reaction as well as the development of post-irradiation radiochemical separation. This paper treats of the problem related to the NAA of trace elements in environmental biochemical toxicology focussing attention of the sources of the elements during the analysis. Typical results and short discussion for every step of the analysis are reported.     

Novel Cholic-Acid-Type Sterones of Deltocyathus magnificus,a deep-water scleractinian coral from the Loyalty Islands,SW Pacific

Cholic-acid-type 3-keto steroids 1–8 , all isolated from Deltocyathus magnificus ( 2–8 after CH₂N₂ treatment), are the first secondary metabolites obtained from a deep-water scleractinian. Steroids 1–3, 5 , and 7 are new, their main structural oddities being loss of C(24) (see 5 ) or hydroxylation in the side chain (see 3 and 7 ). Steroids 4, 6 , and 8 , from the same coral, were previously known from other marine organisms.     

Upper bounds for the eigenvalues of Hessian equations

In this paper, we prove some upper bounds for the Dirichlet eigenvalues of a class of fully nonlinear elliptic equations, namely the Hessian equations.     

Sharp bounds for the first eigenvalue and the torsional rigidity related to some anisotropic operators

In this paper we prove a sharp upper bound for the first Dirichlet eigenvalue of a class of nonlinear elliptic operators which includes the operator , that is the p‐Laplacian, and , namely the pseudo‐p‐Laplacian. Moreover we prove a stability result by means of a suitable isoperimetric deficit. Finally, we give a sharp lower bound for the anisotropic p‐torsional rigidity.     

Receptor‐Bound Conformation of Cilengitide Better Represented by Its Solution‐State Structure than the Solid‐State Structure

The X‐ray crystal and NMR spectroscopic structures of the peptide drug candidate Cilengitide (cyclo(RGDf(NMe)Val)) in various solvents are obtained and compared in addition to the integrin receptor bound conformation. The NMR‐based solution structures exhibit conformations closely resembling the X‐ray structure of Cilengitide bound to the head group of integrin αvβ3. In contrast, the structure of pure Cilengitide recrystallized from methanol reveals a different conformation controlled by the lattice forces of the crystal packing. Molecular modeling studies of the various ligand structures docked to the αvβ3 integrin revealed that utilization of the solid‐state conformation of Cilengitide leads—unlike the solution‐based structures—to a mismatch of the ligand–receptor interactions compared with the experimentally determined structure of the protein–ligand complex. Such discrepancies between solution and crystal conformations of ligands can be misleading during the structure‐based lead optimization process and should thus be taken carefully into account in ligand orientated drug design.