Dedicated to Prof. A. Jerry Kresge on the occasion of his 75th birthdayThe equilibrium between 10H-anthr-9-one and 9-anthrol favors the ketone, which ionizes as a carbon acid in aqueous base. Rates of equilibration were measured over the pH range 1 ± 13 in aqueous solution (258, ionic strength I 0. m). Five independent thermodynamic and kinetic parameters were determined by analysis of the pH-rate profile: the equilibrium constant of enolization, pK E 2.17, the ionization quotient of anthrol, pQ E a 7.84, and the rate constants of enolization catalyzed by acid, k E H 2.2 ¥ 10 À4 m À1 s À1 , base, k E HO À 51.0 m À1 s À1 , and water, k E 0 1.21 ¥ 10 À5 s À1 . Structure-reactivity relationships strongly support the view that pH-independent enolization of anthrone in water proceeds by rate-determining ionization of the C-acid.Introduction. ± KetoÀenol tautomerism is a cornerstone of organic reactivity. Ninety years ago, Meyer [1] achieved the separation of solid 9-anthrol 2 ) (E) from its more stable tautomer 10H-anthr-9-one 3 ) (K). He also determined the equilibrium constant of enolization in EtOH solution,. Subsequent studies have dealt with the solvent [3 ± 9] and temperature [10] dependence of the anthroneanthrol equilibrium. Apolar solvents favor the ketone, hydrogen-bond acceptor solvents such as DMSO favor the enol. Kinetic data were reported for the enolization of anthrone induced by base catalysts in acetonitrile solution [6] and in apolar solvents [5]. The photophysical properties and photochemical reactions of anthrone were also investigated [11 ± 18].Over the last two decades, accurate equilibrium constants of enolization covering thirty orders of magnitude have been determined kinetically, i.e., as ratios of enolization and ketonization rate constants in aqueous solution [19]. Few data are available for compounds with K E close to unity [20,21]. Such data are of interest for free-energy relationships and to determine the intrinsic barrier to proton transfer involving C-atoms. To fill the gap between ketones (pK E % 8) and carboxylic acids or esters (pK E % 18), which strongly favor the keto form, and phenol at the other extreme {pK E (cyclohexa-2,4-dienone) À 12.7 [22]}, we have determined the kinetic and thermodynamic parameters of the anthrone-anthrol equilibrium in H 2 O.

The first structure-activity study involving the 1,2-dithiin class of compounds (1,2-dithiacyclohexadienes) is herein reported. A series of 3,6-disubstituted 1,2-dithiins was synthesized from dithiins 1d and 1e and evaluated as antifungal agents. A new and versatile synthesis of dithiins 1d and 1e is reported which is amenable to scale-up at the kilogram level. The novelty of the process derives from the use of beta-mercaptopropionitrile as the thiophile, relying on a beta-elimination strategy and subsequent oxidation to create the 1,2-dithiin ring. Optimal geometries of dithiins 1d, 18i, and 45 and model dithiin 61 were determined by molecular mechanics and Hartree-Fock molecular orbital calculations. Two possible mechanisms of action are presented for the 1,2-dithiin class of compounds to explain their observed antifungal activities against Candida albicans, Cryptococcus neoformans, and Aspergillus fumigatus.

The syntheses and biological activities of some nitrostyrene derivatives of adenosine 5'-glutarates, a novel class of selective, bi-substrate-type inhibitors of the EGF receptor protein tyrosine kinase, are described. The most interesting compounds (14-16) were able to inhibit the EGF-R tyrosine kinase with IC,, values around 1 p~. Only marginal inhibition of the tyrosine kinases u-ubl and c-src and of the serine/threonine kinase PKC was observed. Compounds 8, 9, 11, and 12 ~ lacking the adenosine moiety -were ten times less active than the most potent derivatives, whereas 17 lacking the nitrostyryl part . -showed no inhibitory activity at all. Most of the compounds showed potent antiproliferative activity against an EGF-dependent mouse keratinocyte cell line.

B-Nitrostyrene derivatives of adenosine 5'-glutarates are potent and selective bisubstrate-type inhibitors of the epidermal growth factor receptor protein tyrosine kinase (EGF-R PTK). In an attempt to improve the inhibitory activity, this type of compounds was modified with alkyl spacers of varying length between the nitrostyrene and the glutaryl units. The spacers consisted of 1, 3,4, and 5 atoms to give compounds of the benzyl, oxyethyl, oxypropyl, and oxybutyl series, respectively (Schemes 1 and 2). Adenosine 5'-esters were prepared in the benzyl and oxypropyl series only. Compared to the compounds in the parent series without spacer (ICs0 = 0.7-12 p~) , most of the modified compounds inhibited the EGF-R PTK only marginally or were inactive (K5, 2 100 VM). The only exceptions were the free acids 19 and 20 with IC,, values of ca. 5 PM. It is noteworthy that esterification of these two hydrogen glutarates with either MeOH or adenosine yielded inactive compounds, which is in contrast to the corresponding substances without spacers.

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