Showing papers by "Jon Clardy published in 1986"

The pseudopterosins: anti-inflammatory and analgesic natural products from the sea whip Pseudopterogorgia elisabethae.

Abstract: The Caribbean sea whip Pseudopterogorgia elisabethae (Octocorallia, Cnidaria) has been found to contain the pseudopterosins, a newly described class of natural products, which have been characterized as diterpene-pentoseglycosides. The pseudopterosins possess anti-inflammatory and analgesic properties that exceed, in our assays, the potencies of existing drugs such as indomethacin. As anti-inflammatory agents, the pseudopterosins appear to modify the arachidonic acid cascade by an as yet undefined mechanism of pharmacological action.

Solid-state and solution studies of lithiated 2-carbomethoxycyclohexanone dimethylhydrazone and lithiated cyclohexanone phenylimine

Abstract: Treatment of 2-carbomethoxycyclohexanone dimethylhydrazone with lithium diisopropylamide as a hydrocarbon solution afforded the corresponding lithiated hydrazone as a tetrahydrofuran solvate 1. An X-ray crystallographic structure determination showed 1 to be dimeric in the solid state. Solution molecular weight and spectroscopic studies in aromatic hydrocarbon solvents uncovered a dissociative process involving either monomer-dimer equilibrium or solvent dissociation. Treatment of cyclohexanone phenylimine with lithium diisopropylamide in hydrocarbon solution afforded the corresponding lithiated derivative as the diisopropylamine solvate 2. An X-ray crystallographic structure determination showed 2 to exist as a dimer with significant disorder in the cyclohexenyl and phenyl moieties. Lithium-xrbon contacts of the q3-azaallyl type were not observed. 6Li and \"C NMR studies showed 2 to exist as a 2:l mixture of two rapidly equilibrating forms. By titration of the corresponding solvent-free anion (2sobcnt.frce) with diisopropylamine, the two species were shown to be bis-solvated dimers in close analogy to the solid-state structure. The structures are discussed in light of the stereochemistry of imine alkylation and the syn effect of lithiated imines. We became interested in the mechanism of the alkylations of metalated Schiff s bases (azaallyilithiums).l~* Although on first inspection the C=N-R moiety and C=O ketone carbonyl group appear to be interchangeable, studies by Corey, Enders, Fraser, and others uncovered some notable differences in the alkylation stere~selectivities.~~~ For example, metalated Schiffs bases derived from conformationally anchored cyclohexanones exhibit axial (1) Collum, D. B.; Kahne, D.; Gut, S. A,; Dehe, R. T.; Mohamadi, F.; Wanat, R. A,; Clardy, J.; Van Duyne, G. J . Am. Chem. Soc. 1985,106,4865. (2) Wanat, R. A,; Collum, D. B. J . Am. Chem. Soc. 1985, 107, 2078. (3) Reviews of the chemistry of metalated Schiffs bases: (a) Hickmott, P. W. Tetrahedron 1982, 38, 1975. (b) Enders, D. In Currenf Trends in Organic Synthesis; Nozaki, H., Ed.; Pergamon: New York, 1983. (c) Whitesell, J. K.; Whitesell, M. A. Synthesis 1983, 517. (d) Fraser, R. R. In Comprehensive Carbanion Chemistry; Elsevior: New York, 1980. (4) The nitroso derivatives of 4-terr-butylpiperidines exhibit high alkylation stereoselectivities that seem to imply a close mechanistic relationship to lithiated Schiffs base alkylations (cf. ref 3d). alkylation selectivities of a significantly greater magnitude than those of the corresponding ketone enolates (eq l).5 In the specific case of dimethylhydrazone alkylation, the axial selectivities are sensitive to substituents on the carbanionic carbon. Cyanoand (methy1thio)-substituted lithiated hydrazones alkylate with high axial selectivities. However, the corresponding carbomethoxysubstituted derivative exhibits a lower selectivity more characteristic of ketone enolates. Equally intriguing is the propensity of the 3and 6-substituted lithiated cyclohexanone dimethylhydrazones to alkylate from the more hindered face.' ( 5 ) Huff, B. J. L.; Tuller, F. N.; Caine, D. J. Org. Chem. 1969, 34, 3070. House, H. 0.; Umen, M. J. J. Org. Chem. 1973, 38, 1000. Howe, R.; McQuillin, F. J. J. Chem. SOC. 1958, 1194. Kuwajima, 1.; Nakamura, E. J . Am. Chem. SOC. 1975, 97, 3257. Djerassi, C.; Osiecki, J.; Eisenbraun, E. J. J. Am. Chem. Soc. 1%1,83,4433. House, H. 0.; Tefertiller, B. A,; Olmstead, H. D. J. Org. Chem. 1968,33,935. Kuehne, M. E. J . Org. Chem. 1970,35, 171. Kuwajima, I.; Nakamura, E.; Shimizu, M. J . Am. Chem. Soc. 1982,204, 1025. 0002-7863/86/1508-3415$01.50/0

Absolute configuration of brevetoxins

Abstract: The absolute configuration of the dinoflagellate toxins, brevetoxins, has been unequivocally determined by X-ray crystallography of a chiral dioxolane derivative.

PD 116,152, a new phenazine antitumor antibiotic. Structure and antitumor activity.

Abstract: A new, highly substituted phenazine with antitumor activity was isolated from the culture broth of a Streptomyces sp. This compound, whose structure was determined by spectroscopic methods and verified by X-ray diffraction analysis, was found to be methyl 6-formyl-4,7,9-trihydroxy-8-methyl-1-phenazinecarboxylate.

X-ray Diffraction and Marine Natural Products

Abstract: While natural products research has expanded into many new areas of inquiry, the traditional goal of describing the molecular structure of a naturally occurring substance has not diminished in importance. A secure molecular structure is still the common starting point for synthetic, biosynthetic, and even some biological endeavors. In this paper I will explain why x-ray diffraction is increasingly the method of choice for structure elucidation and illustrate its utility with some recent applications to marine natural products.