"One of the most surprising things," Magnus says, is the next step: conversion to a hexacyclic molecule via a carbanion intermediate with complete retention of optical configuration at C-ll, the site of the carbanion. This reaction "was completely unexpected," he explains, and it is the only example he knows of where there is complete retention of configuration of a carbanion next to a carbonyl group. Magnus and Gallagher then carried out an intramolecular DielsAlder reaction to form the basic heptacyclic kopsane skeleton. A reduction reaction followed by an oxidation reaction produces a sulfoxide. This sulfoxide undergoes "an extraordinary reaction," Magnus observes. It undergoes eliminationaddition at 230 °C (usual reaction conditions are at about 120 °C) to move the phenylsulfoxide functional group from C-ll to the adjacent C-22. Magnus believes that the reaction must proceed through an intermediate anti-Bredt compound. (According to Bredt's rule, such a highly strained molecule would be extremely difficult to form.) The Indiana scientists use a second Pummerer reaction, followed by reduction and oxidation reactions, to produce the final product—(±)10,22-dioxokopsane. Their 14-step reaction scheme provides an overall yield of 5.8%. Magnus considers this "a pretty short number of steps and an excellent yield for synthesis" of that complex a structure. Furthermore, modification of the last two steps of the reaction scheme produces (zfc)-kopsanone, which differs from 10,22-dioxokopsane only in the former's lack of a carbonyl group atC-10. Magnus hopes the synthetic scheme will prove applicable to preparation of other compounds— for example, by use of the unusual reaction step involving a carbanion intermediate. He will try reactions on model compounds that are structurally similar to a small section of the pentacyclic molecule around the carbanion, assuming that the reaction does not require all of the pentacyclic molecule. The potent biological activity of the kopsanes is another major reason
azuloquinones at the national meeting of the American Chemical Society in Seattle. He also described trapping 1,4- and 1,6-azuloquinones, which are predicted to be less stable, as cyclopentadiene adducts. An additional dividend of Scott's work is that the azuloquinones he isolated show promise as anticancer drugs similar to some benzenoid quinones. He says that the 1,5- and 1,7-azuloquinones show significant cytotoxicity in a certain cell-culture screening test. Also, Scott has converted azuloquinones to heptaloquinones, which might be another series useful for comparing experimental with calculated properties. Scott first set the stage to use azuloquinones as test cases three years ago in work with chemistry professor Kendall N. Houk and graduate student Melvin D. Rozeboom, who then Chemists have made the first three of were at Louisiana State University, the 16 possible quinones of azulene Baton Rouge; chemist Tada Fukunaga as a test of current theories of aro- of Du Pont, Wilmington, Del.; and matic structure, bonding, and reac- chemistry professors Hans Jorg tivity. Because theoretical calcula- Lindner and Klaus Hafner of Darmtions are better at predicting values stadt Technical College, West Gerof relative rather than absolute many [/. Am. Chem. Soc, 102, 5169 properties, comparisons among a set (1980)]. These collaborators used ab of isomers would be valuable to test initio and semiempirical quantum mechanical methods to predict such methods. Organic chemistry professor properties as heats of formation, ulLawrence T. Scott of the University traviolet/visible spectra, electroof Nevada, Reno, described the syn- chemical reduction potentials, and Continued on page 57 thesis and isolation of 1,5- and 1,7for interest in the synthesis. Kopsanes were once thought, erroneously, to belong to the same structural family as the heptacyclic indole alkaloid strychnine, he points out. This was because kopsanes exhibit biological activity resembling strychnine's—they stimulate the central nervous system, but, unlike strychnine, do not cause death. Magnus views the work on synthesis of kopsanes as a prelude to his planned preparation of the yet more complex dimeric indole alkaloids, such as pleiomutine. One dimeric indole alkaloid, vinblastine, is already in routine clinical use as an antileukemic drug, he says. D
First quinones of azulene prepared
Scott at work in his lab, where he and a coworker isolated two azuloquinones April 18, 1983 C&EN
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Science Three quinones are stable enough to be isolated to date...
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reactivities of the 16 azuloqui nones. Even as they finished their pre dictions, word came from Tohoku University, Sendai, Japan, that chemistry professor Tadayoshi Morita had made 1,2-azuloquinone. The compound was green, as Scott and his collaborators had predicted it would be. The 1,2-quinone had UV/ visible maxima at 594 nm and 386 nm. The U.S. workers had calculated maxima at 572 nm and 397 nm. In Seattle, Scott's graduate student, Christopher M. Adams, described work supported by the National In stitutes of Health to make the 1,5and 1,7-compounds. The Nevada workers obtained a properly substi tuted azulene intermediate by pho tolysis of hydrocinnamoyldiazomethane. The 1,5-azuloquinone is yellow and the 1,7-isomer is yellow with an orange tinge, as expected. The longest 7r-to-7r* transition had been calculated to lie at 371 nm for the 1,5-quinone and at 394 nm for the 1,7-derivative. Adams and Scott found these at 373 nm and 384 nm, tailing off into the visible region to give the colors. Scott is encouraged by the successful color predictions. He says that making other members of the series will be easier if chemists know what colors to expect.
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Future work at Nevada will in clude measuring relative rates of re actions with nucleophiles, DielsAlder reactions, and dimerizations; reduction potentials; and ultimately calorimetry to determine heats of formation, if the required 1-g amounts of the azuloquinones can be spared. As an index of electrophilicity, Scott reacted isolated azuloquinones with 1-diethylaminopropyne to get 4-diethylamino-3-methyl-l,7- and 1,9-heptaloquinones. These product structures indicate that the more negative part of the reagent adds to the carbon atom calculated to be the more electrophilic carbon to yield a tricyclic intermediate, 5-diethylamino - 4 - methyltricyclo[5.5.03'6]dodeca -4,7,10,12-te traene-2,9-dione, in the case of 1,5-azuloquinone. The reaction also makes heptaloquinones available for study. Scott could not isolate 1,4- or 1,6azuloquinones. Working with post doctoral student Peter Grutter and graduate student Raymond E. Chamberlain III, he carried out the last reactions to form these com pounds in the presence of cyclopentadiene. These gave adducts with the exposed double bonds of the cyclopentadienone moieties of the qui nones. D
Metal catalysts snared in synthetic vesicles Put simply, when catalytic metalcolloid particles are made smaller and more uniform, they work better. Speaking at the national meeting of the American Chemical Society in Seattle, members of several research groups, including that of Janos H. Fendler—this year's recipient of the Kendall Award—described their ef forts to use micelles and vesicles to achieve this goal. Metal catalysts can be trapped readily in micrpemulsions and in synthetic vesicles made of surfactant molecules, according to Fendler, chemistry professor at Clarkson College of Technology, Potsdam, N.Y. "I prefer the vesicles because they allow a greater degree of orga nization/' he says. Moreover, the way they're formed about the metal helps to ensure greater stability of the complex. Thus, Fendler and his colleagues have devised a method whereby, si multaneously, the included metal is photoreduced and the styrene-containing surfactant monomers of the vesicle are photopolymerized. This leads to "enhanced stability," he notes. Because such vesicles remain freely permeable to gases, the whole unit can be used for carrying out cat alytic hydrogénations, for example. The question of whether such vesicles can be adapted for other catalytic purposes involving reactions in liquid phase is still largely unanswered, Fendler notes. It ought to be possible to freeze-dry such vesicles for use in fluidized beds. Alternatively, channels in vesicle surfaces might be formed to allow reactants to enter and products to leave without losing the catalyst. Pursuing such possibilities could prove well worth the effort. Thus, for example, J. B. Nagy and his colleagues at Facultés Universitaires Notre-Dame de la Paix in Namur, Belgium, are studying iron and nickel borides enclosed in reversed micelles. Such structures improve on catalytic efficiency, Nagy reported at the ACS meeting. Though Fendler hasn't yet tested the catalytic efficiency of his vesicles, he's encouraged by Nagy's results. D April 18, 1983 C&EN 57
