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Ripostatins are polyene macrolactones isolated from the myxobacterium Sorangium cellulosum. They exhibit antibiotic activity by inhibiting bacterial RNA polymerase (RNAP) through a binding site and mechanism that are different from those of current antibacterial drugs. Thus, the ripostatins serve as starting points for the development of new anti-infective agents with a novel mode of action. In this work, several derivatives of ripostatins were produced. 15-Desoxyripostatin A was synthesized by using a one-pot carboalumination/cross-coupling. 5,6-Dihydroripostatin A was constructed by utilizing an intramolecular Suzuki cross-coupling macrolactonization approach. 14,14'-Difluororipostatin A and both epimeric 14,14'-difluororipostatins B were synthesized by using a Reformatsky type aldol addition of a haloketone, Stille cross-coupling, and ring-closing metathesis. The RNAP-inhibitory and antibacterial activities are presented. Structure-activity relationships indicate that the monocyclic keto-ol form of ripostatin A is the active form of ripostatin A, that the ripostatin C5-C6 unsaturation is important for activity, and that C14 geminal difluorination of ripostatin B results in no loss of activity.

The palladium-catalysed α-chloro ketone methoxycarbonylation and allylic alkylation reactions can be efficiently combined to provide a new catalytic domino reaction. The first, carbonylative, step generates the β-keto ester, which acts as the nucleophile in a subsequent allylation step. The use of allyl phenates in combination with Xantphos ligand are the key features allowing one to obtain the allylated β-keto esters in good yields.

Reactions of electron-poor α-haloketones with (N-isocyanimino) triphenylphosphorane in the presence of aromatic carboxylic acids proceed smoothly at room temperature and in neutral conditions to afford disubstituted 1,3,4-oxadiazole derivatives in high yields. © 2010 Wiley Periodicals, Inc. Heteroatom Chem 21:368–372, 2010; View this article online at wileyonlinelibrary.com. DOI 10.1002/hc.20626

Several [18F]-labeled α-trifluoromethyl ketones have been synthesized. Reactions of 2,2-difluoro-1-aryl-1-trimethylsiloxyethenes (1a–d) with [18F]-F2 at low temperature produced [18F]-labeled α-trifluoromethyl ketones (2a–d). Radio-labeled products were isolated by purification with column chromatography in 22–28% yields, decay corrected (d.c.) in three runs per compound. Radiochemical purity was >99% with specific activities 15–20 GBq/mmol at the end of synthesis (EOS). The synthesis time was 35–40 min from the end of bombardment (EOB). This one-step simple method is highly useful for the radiochemical synthesis of potential biologically active [18F]-labeled α-trifluoromethyl ketones for PET imaging. Copyright © 2003 John Wiley & Sons, Ltd.

Carbon-14 labeled 4-[4-[2-[2-[bis(4-chlorophenyl)methoxyethylsulfonyl] [1-14C]ethoxy]phenyl]-1,1,1-trifluoro-2-butanone was prepared in a six step radioactive synthesis from 2-bromo[1-14C]acetic acid. The overall radiochemical yield was 2.2%. The specific activity of the final product was found to be 42μCi/mg with a radiochemical purity of >98%. Copyright © 2002 John Wiley & Sons, Ltd.

To assess the potential of intermolecular hydroacylation reactions as a new fluorine-18 labeling method, model reactions of [18F]fluorobenzaldehyde with three different olefins (1-hexene (2a), allylbenzene (2b), and 3-phenoxypropene (2c)) in the presence of Wilkinson's catalyst were performed. The procedure gave high radiochemical yields (38–62%) of [18F]fluorophenylketones with short reaction times (15 min). The intermolecular hydroacylation reaction provides a new method for the preparation of fluorine-18 labeled compounds. Copyright © 2002 John Wiley & Sons, Ltd.

An efficient synthesis of [4-14C]-5α-Androstan-16α-bromo-3β-ol-17-one (1) via the intermediate [4-14C] testosterone (8) is described. This compound targets cellular metabolic pathways and clinical trials to HIV-viral pathogenicity are promising. Copyright © 2000 John Wiley & Sons, Ltd.

Using a combination of solid phase synthesis for the preparation of N-substituted-N-acylglycines 7 followed by solution-phase ring transformation of trifluoromethylacyl munchnone intermediate 8, a library of 200 trisubstituted-5-trifluoromethylketo (TFMK) imidazoles 9 was prepared. In a sublibrary, bromoacetate resin 4 was treated with 5 amines in parallel to give N-substituted glycines 5 followed by acylation with 12 acid chlorides to provide, upon cleavage from the resin, 60 individual N-substituted-N-acylglycines 7. The glycines 7 were converted to munchnones 8 by treatment with trifluoroacetic anhydride followed by reaction with benzamidine to give trisubstituted-5-TFMK-imidazoles 9. The structural content of the library was analyzed using PlateView of the LCMS results, and individual members were isolated by automated preparative LCMS.

The 1,2-dithiolanes 1 and 2 and the 1,2-dithianes 3–5 were prepared from the dibromoalkanones 14–18 and Li2S2. Whereas the five-membered systems 1 and 2 were readily formed, the six-membered derivatives 3–5 occurred always together with various amounts of the monothiacyclopentanes 11–13. The 1,3-dithia compounds 6–10 were prepared from the dibromoalkanes 19, 20, 14–16 and HSCH2SH in pyridine. The synthesis of the precursors 14–20 is described. Flavour evaluation showed that particularly 2, but also 1 and 3–8 (previously isolated from meat flavour model systems) should contribute with their fatty, spicy, roasty, mushroom and sulphury notes to the total meat flavour complex. © 1998 John Wiley & Sons, Ltd.

Side-chain fluorinated 15-ketosterols are potent regulators of sterol synthesis. For investigations of their metabolism, we have prepared 3β-hydroxy-25,26,26,26,27,27,27-heptafluoro-5α-cholest-8(14)-en-15-one and its 7α-methyl and 8(14)-saturated derivatives with one deuterium or tritum atom at C-23. The isotopic hydrogen was introduced by reduction of 23-iodo-15-ketosterols with tributyltin deuteride or tritide. Mass spectral analyses of the deuterated sterols showed incorporation of one deuterium in the side chain, and 2H and 13C NMR showed that deuterium was present only at C-23. The tritiated sterols had specific activities of 82-179 mCi/mmol and showed high radiochemical purities. © 1998 John Wiley & Sons, Ltd.

The protease inhibitor (S)-1-chloro-3-[(p-tolylsulfonyl)amino]-7-amino-2-[5,5,6,6-3H]heptanone ([ 3 H]TLCK) was prepared in an overall 41% radiochemical yield with a specific activity of 1.6 Ci/mmol in a'one-pot' 3 step sequence beginning with (S)-6-[[(1,1-dimethylethyl)oxy]carbonyl]-2-(p-tolylsulfonyl)amino[4,4,5,5- 3 H]hexanoic acid. The latter was prepared with a specific activity of 123 Ci/mmol in a 3 step sequence beginning with the stereospecific enzymatic hydrolysis of the commercially available racemic 2-acetylamino-6-[[(1,1-dimethylethyl)-oxy]carbonyl]aminohexan-4-ynoic acid, followed by tosylation and then palladium catalyzed reduction of the triple bond under tritium.

Ro41-0960 (3,4-dihydroxy-5-nitro-2′-fluorobenzophenone) is a potent, fluorine containing COMT inhibitor. In order to map catechol-O-methyltransferase (COMT) in vivo with PET, no-carrier-added [18F]Ro41-0960 was synthesized by the nucleophilic aromatic substitution of [18F]fluoride for 2′-nitro on 3,4-dimethoxy-5,2′-dinitrobenzophenone, followed by hydrolysis with HBr. During the course of this study it was found that [18F]fluoromethane ([18F]CH3F) was generated as the side product of nucleophilic aromatic substitution reaction. Various precursors with different hydroxyl protecting groups were then investigated for the effects on this side reaction. © 1997 John Wiley & Sons, Ltd.

Aromatic aldehydes or ketones which have electron-withdrawing groups on the benzene ring were selectively reduced to the corresponding alcohols in good yields by sodium hydrogentelluride; common aldehydes such as benzaldehyde and tolualdehyde were inert.

Sonication of a zinc/copper couple, N,O-bis(trimethylsilyl)-acetamide (BSA) and α,α'-oligobromo ketones in benzene gives rise to oxyallyl intermediates which cycloadd to anthracene. Starting from 1,1,3,3-tetrabromoacetone (2a) and anthracene (1a), we obtained 11,11,13-tribrominated adduct 4 as the major product (42%). The expected 11,13-dibrominated adduct trans-3 was formed as a minor product (5%), but it became the main product when the known oxyallyl methodology was applied. Dibenzohomobarrelenes 9 and 17 were prepared by short routes.

The selective bromination with copper(II) bromide of the pyrrole ring in 2-(2'-hydroxybenzoyl)pyrrole (II) in the heterogeneous phase is des- cribed giving in almost quantitative yield the 4,5-dibromo derivative (VI). The subsequent introduction of halogen into the phenol moiety was observed when the reaction was perfomed in the homogeneous phase with an excess of halogenating agent. The pentabromo derivative (IX), a com- pound very active against Staphylococcus aureus (mic=17 nmoles per dm -3 ), was obtained by exhaustive bromination of the title compound. Poor yields of chloro derivatives of (II) were obtained by reaction of the parent compound with copper(II) chloride

An azido-125iodo-ansamycin (1) in the geldanamycin family was prepared in two steps in one reacton vessel from 17-amino-22-(4′-aminophenacyl)-17-demethoxygeldanamycin (3). The title compound was suitable for photoaffinity labeling proteins that interacted with ansamycins. A alternative synthesis is reported for preparation of unlabeled title compound in order to afford practical amounts of (1) for conventional biochemical studies.

The preparation of hitherto unknown trifluoromethyl substituted 2-amino-3,4,6-triarylbenzophenones 3 by a 2,5-[C4+C2] rins transformation of 2,4,6-triarylpyrylium salts 1 with trifluoromethylbenzyl cyanides 2 in the presence of sodium methanolate in methanol is reported. Spectroscopic data of the benzophenones 3 and the mode of their formation are discussed.

A versatile synthetic method for preparing 1-substituted 3-nitroquinolin-4(1H)-ones from corresponding 2-fluoro-α-nitroacetophenones is demonstrated by the synthesis of 6,7-difluoro derivatives 7a-c. The method involves sequential treatment of the starting nitroacetophenone with triethyl orthoformate and the appropriate amine, followed by a nucleophilic cyclization reaction under mild conditions. The C-7 fluorine atom of 7 can be displaced by cyclic amines. Substituted 6-fluoro-7-(4-methyl-1-piperazinyl)-3-nitroquinolin-4(1H)-ones 8a-c were prepared in this way.

Conformation and Bromination of Bicyclo[3.3.1]nonane-2,6-dione and Dehydrobromination of the Bromo Ketones. – Improved Synthesis of Bicyclo[3.3.1]nona-3,7-diene-2,6-dione Bromination by copper(II) bromide of bicyclo[3.3.1]nonane-2,6-dione (1) affords the epimeric α-bromo diketones exo-and endo-5 and, eventually, the α, α′-dibromo diketones exo- and endo-7 (3:7) in high yield. Dehydrobromination of the mixtures of bromo diketones by calcium carbonate in dimethylacetamide yields the unsaturated diketones 6 (30%) and 2 (72%), respectively. Bromination of 1 by molecular bromine is less selective and furnishes mixtures of brominated diketones consisting of exo- and endo-7, 8 and the tetrabromo diketone 10. An excess of bromine yields pure 10. – The ethylene acetal 12 is brominated by pyridinium perbromide to produce the α,α′-dibromo acetal 13 which is very reluctant towards 1,2-dehydrobromination by potassium tert-butoxide. Thus, with an excess of potassium tert-butoxide in tetrahydrofuran, 1,2-dehydrobromination is achieved only on one side to afford 14. In contrast, potassium tert-butoxide in dimethyl sulphoxide induces a transannular dehydrobromination leading to the diacetal 15 of 3-bromonoradamantane-2,6-dione. – The conformations of 1,10, and 13 in the solid state are determined by X-ray diffraction analyses. From torsional angles, vicinal proton coupling constants are calculated with the aid of the Karplus equation and compared to those determined from solutions by high-field NMR spectroscopy. The reasonable agreement provides the basis for the assessment of the configuration and conformation for exo- and endo-7.

exo-7-Chloro-endo-7-phenylbicyclo[3.2.0]hept-2-en-6-one (5) undergoes cine substitution reactions with methoxide anions and with dialkylamines to give 5-methoxy or 5-dialkylamino derivatives 13, 14, 16–19 in high yield. While attempts directed to an acetalization have failed, the addition of Grignard reagents to the methoxy derivatives proceeds stereoselectively in high yield. Hydrochlorides 20/21 lose amine at 110°C to form 2-phenyltropone (22). Thermolysis of diethylamino derivative 24 at 170°C (temperature determined by DSC) results in the formation of the dienaminone 25.

A convenient approach to aryl 3-pyridazinyl ketones (4), (7-10) bearing various O-, N-, or C-substituents at C-6 of the diazine nucleus via oxidative decyanation of appropriate aryl-heteroaryl- acetonitriles is proposed

Stereoselective Synthesis of 3-Substituted Cyclobutanols and Products Derived Therefrom 3-Substituted cyclobutanones 2 are prepared by alkene/dichloroketene cycloadditions and subsequent dehalogenation. Reduction with LiAlH(OtBu)3 furnishes cis-cyclobutanols 3 in 95–100% selectivity. Mitsunobu inversion turned out to be the only practical method to get trans isomers 4 in high selectivity. A stereoselective cyclobutanolbromocyclobutane conversion could be achieved only by a modified Mitsunobu reaction. Cross coupling between zinc derivatives of bromocyclobutanes 9 and aromatic bromides is not stereoselective.

Diastereomeric 5α-cholestane-3,3′-spiro-2′,2′-dichlorocyclobutanones 1 and 2 served as starting materials for the synthesis of related heterocyclic spirane derivatives. Thus, diastereomeric 5α-cholestane-3,3′-spiropyrrolidin-5′-one (10, 11), -3′-spiro-γ-lactone (12, 16), and -3′-spirotetrahydrofuran (14, 18) are described. The spirocyclobutanone oximes (E)-4 and (Z)-5 and their O-acetyl and O-benzoyl derivatives 6, 7 and 8, 9 are also prepared. It has been shown that the Beckmann rearrangement of the spirocyclobutanone oximes 4 and 5 proceeds stereospecifically with exclusive anti migration. The stereochemistry of the spiro compounds is assigned on the basis of the 1H- and 13C-NMR spectral data.

Syntheses of (+/-)-2-exo-cyano-1-methyl-7-oxabicyclo[2.2.1]hept-5-en-2-endo-yl acetate (1) and of (+/-)-1-methyl-7-oxabicyclo[2.2.1]hept-5-en-2-one (2) are reported. The additon of PhSeCl to 1 afforded (+/-)-5-endo-chloro-2-exo-cyano-1-methyl-6-exo-(phenylselenenyl)-7-oxabi cyclo[2.2.1]hept-2-endo-yl acetate (6), whereas 2 added to PhSeCl with the opposite regioselectivity giving (+/-)-6-endo-chloro-1-methyl-5-exo-(phenylselenenyl)-7-oxabicyclo[2.2.1] heptan-2-one (7). These adducts were converted into 5-chloro-1-methyl-7-oxabicyclo[2.2.1]hept-5-en-2-one (9) and 6-chloro-1-methyl-7-oxabicyclo[2.2.1]hept-5-en-2-one (10), respectively.

The investigation reported here describes an attempt to establish the structure of the intermediate that undergoes ring-opening in the chlorination of resorcinol and its chloro-derivatives in a nucleophilic solvent such as H2O or CH3OH. The evidence suggests that the pentachloride and not the tetrachloride is the intermediate that reacts with the nucleophiles. Chlorination reactions were conducted in CH3OH/H2O. The structures of the “early-generation” products from incorporation of CH3OH were sufficiently stable to be characterized. These products implicated the pentachloride. Resorcinol, di- and trichlororesorcinol, and the pentachloride gave the same products. The mechanisms of the ring-opening and the reactions leading to the products are described in detail. The assumption is made that the same or similar reactions are involved in the aqueous chlorination of resorcinol, but that decarboxylation and solvolysis reactions rapidly degrade the products immediately following ring-opening.

The acid-catalyzed cyclization of a pseudogeminally substituted acetyl group and a chloromethyl group of tri-bridged cyclophane 7, followed by reduction of the carbonyl group afforded [3 4 ](1,2,3,5)cyclophane 3. One-step TosMIC coupling reaction of tetrabromide 12 and subsequent reduction of the carbonyl groups provided an isomer of 3, [3 4 ](1,2,4,5)cyclophane 4

The endocyclic replacement of a nitrogen atom at the 1-position of quinolone antibacterial nucleus with a sulfur atom was investigated. A series of 1-benzothiopyran-4-one-3-carboxylic acids 14-16 and isothiazolo[5,4-b][1]benzothiopyran-3,4-diones 22-24, suitably functionalized with a fluorine atom at C-6 and heterocyclic base at C-7, were prepared. The antibacterial evaluation of the target compounds showed an activity comparable to that of nalidixic acid for compounds 14-16, while an increased activity against gram-positive bacteria was observed for compounds 22-24

Diastereomeric [(3S)-5α]- and [(3R)-5α]-2′,2′-dichlorospiro-[cholestane-3,1′-cyclobutan]-3′-ones (1 and 2), prepared by cycloaddition reaction of dichloroketene with 3-methylene-5α-cholestane, served as starting material for the synthesis of the related spirane derivatives. Thus, the synthesis of spiro-cyclopentane (3–6), spirocyclobutane (9, 11, 13, 17–20) and spirocyclopropane steroids (12, 14, 15) is described. The sterically dependent reaction of spiro-α,α-dichlorocyclobutan-3-ones with an excess of sodium methanolate in methanol is reported. Thus, the reaction of 1 with sodium methanolate gives 9, the product of the double cine substitution, while the corresponding reaction of compound 2, which is sterically more hindered for similar nucleophilic attack, gives mainly the spirocyclopropane 12. The stereochemistry of the spiro compounds is assigned on the basis of 1H- and 13C-NMR spectra.

(tert1-Butylisonitrile)copper(I) Complexes with Acetylacetonato-or η51-Cyclopentadienyl Ligands Copper(I) complexes of the type acacCu(CNtBu) (1) and CpCu(CNtBu) (2) are accessible by the reaction of [ClCu-(CNtBu)]4 with M(β1-diket) or MCp (MLi, Na, K, Tl), respectively. hfacCu(CNtBu)2 (3) and hfacCu(CNtBu)3 (4) are prepared by adding molar amounts of tBuNC to hfacCu(CNtBu) (1b).

3H-mometasone furoate was synthesized by a six step procedure. The label was introduced via the reduction and re-oxidation of the 1,2 double bond in the A ring. The remaining 4 steps were accomplished with on overall radiochemical yield of 28%. Analysis by 3H nmr indicated that most of the label (≈95%) was located in the 2-position and the remainder in the 1-position.

To develop new radioligands labelled with radioiodine (125I, 131I and 121I) for in vitro and in vivo dopamine receptor studies, three iodinated butyrophenones (2′-iodospiperone, 2′-iodotrifluperidol and 2′-iodohaloperidol) were designed, synthesized and labelled with 125I.

10 ist ein β-Carbolin-Analogon des Neuroleptikums Flutrolin2a,b) mit deutlich geringerer Affinitat zum Dopamin D2-Rezeptor. Verschiedene Synthesewege zu 10 und die Molekulstruktur im Kristall von 8 werden beschrieben, Struktur-Wirkungsbeziehungen, insbesondere die Bedeutung der “S-shape” - und rigidisierten Dopamin-Konformation diskutiert. Indoles X: Synthesis, Structure and D2-Affinity of the β-Carboline-Analogue of Flutroline 10 is a β-carboline analogue of the neuroleptic flutroline2a,b) with significant lower affinity at the dopamine D2 binding site. Various synthetic routes to 10 and the solid state structure of 8 are described, structure activity relations, in particular the importance of the “S-shape” and the rigid dopamine conformation are discussed.

Reactions of electron-poor α-haloketones with (N-isocyanimino) triphenylphosphorane in the presence of aromatic carboxylic acids proceed smoothly at room temperature and in neutral conditions to afford disubstituted 1,3,4-oxadiazole derivatives in high yields. © 2010 Wiley Periodicals, Inc. Heteroatom Chem 21:368–372, 2010; View this article online at wileyonlinelibrary.com. DOI 10.1002/hc.20626

N-protected α-amino epoxides of erythro configuration, derived from α-amino acids, were synthesized in a stereoselective manner. The erythro (2S,3S) configu- ration was achieved by the synthetic sequence: amino acid → haloketone → halohydrin → epoxide. A mechanistic explanation for the observed stereoselectivity is presented. This stereoselective synthetic approach was applied to the synthesis of a variety of short peptidyl epoxides, bearing a predefined absolute configuration of the chiral epoxide moiety.

Erythro N-protected α-amino epoxides, derived from α-amino acids bearing functionalized side chains, were synthesized. The key synthetic step is a stereoselective reduction of the corresponding haloketone either to the halohydrin or directly to the epoxide. The side chains include ester, ether and alcohol, nitro guanidine, carbamate and amine functional groups, derived from aspartate and glutamate, serine, arginine, and lysine, respectively. The epoxides derived from lysine and Nϖ-nitro-arginine exhibited selective inactivation of the cysteine proteases papain and cathepsin B, while they failed to inactivate the serine protease trypsin.

A study for determining the scope and limitations of a procedure for synthesising ethylene acetals from haloketones is presented. The method uses 1,2-bis(trimethylsilyloxy)ethane, BTSE, as reagent and Nafion®-TMS as catalyst. Two procedures have been tested: (A) stoichiometric amounts of the haloketone and BTSE and a catalytic amount of Nafion®-TMS were heated to reflux in chloroform solution, and (B) stoichiometric amounts of the reactants and a catalytic amount of Nafion®-TMS were heated to 90–100 °C in the absence of solvent. The following ketones have been tested: 2-bromo-1-phenyl-1-ethanone, 2-bromo-cyclopentenone, 3-bromo-3-methyl-2-butanone, 3-chloro-3-methyl-2-butanone, 1-bromo-3,3-dimethyl-2-butanone, 1-chloro-3,3-dimethyl-2-butanone, 2-bromocyclohexanone, 2-chloro-1-cyclohexyl-1-ethanone, 1,1-dibromo-3,3-dimethyl-2-butanone, 1,3-dibromo-3-methyl-2-butanone, 1,3-dibromo-2-butanone, 1,3-dibromo-2-propanone, 2-chloro-1-phenyl-1-ethanone, and endo-2-bromocamphor. Yields were in the range 57–100% with the exceptions of endo-2-bromocamphor which afforded

A variety of 9,10–dihydro–9,10–propanoanthracen–12–ones 1–11 has been prepared from anthracenes 15–23, α,α′-dibromo ketones 12–14 and zinc/copper couple by using dioxane as solvent and ultrasonication at 15–20°C. 2,2,4,4–Tetrabromoacetone (12) afforded cycloadducts, in which the two bromine atoms at C–11 and C–13 are introduced stereoselectively cis and adopt a syndiaxial instead of a cis-diequatorial position (5 examples). Even the cis-configurated methyl groups in adducts 8, 9 and cis-11 adopt syndiaxial positions preferentially.

2-Bromo-3-substituted-inden-1-ones 2 reacted with L-cysteine or 2-aminobenzenethiol to produce 2,3-dihydro-5-phenylindeno[2,1-b][1,4]thiazine in moderate yield or 6-substituted-indeno[2,1-b][1,4]benzothiazines in good yield. The debrominated oxime and the phenylhydrazone of 2 were separated into their respective E- and Z-conformers by column chromatography and their E- and Z-configurations were obtained from the 1 H nmr spectra

Reactions of tetrasulfur tetranitride (S 4 N 4 ) with aryl and alkyl bromomethyl ketones 1 in chlorobenzene at reflux temperature gave 3,5-diaroyl- and 3,5-diacyl-1,2,4-thiadiazoles 2 in 17-60% yields. No 1,2,5-thiadiazoles were detected. By heating of the two reactants at 115° without the solvent were also obtained 2 in 5-13% yields. Hydrolysis of 2 with sodium hydroxide in a mixture of ethanol, ethyl acetate, and water (v:v, 4:2:1) at 75 o to 85 o afforded the heretofore inaccessible 3-aroyl- and 3-acyl-1,2,4-thiadiazoles 5 in 17-79% yields

(Thiazolylethenyl)phenols were prepared as potential antiinflammatories by reaction of thiazole 4- and 5-acetic acid derivatives with 3,5-di-tert-butyl-4-hydroxybenzaldehyde. Alternatively, an arylethenyl methyl ketone was brominated and the bromoketone product reacted with methyl dithiocarbamate, ammonium dithiocarbamate, or thiourea.

Aromatic ketones react with 3-mercapto-1,2-propanediol (1) in refluxing benzene under the catalytic influence of a sulfonic acid and with azeotropic removal of water to yield a mixture comprised predominantly of cis- and trans-2-alkyl-2-aryl-1,3-oxathiolane-5-methanols 7, accompanied by lesser amounts of cis- and trans-2-alkyl-2-aryl-1,3-dioxolane-4-methanethiols 8 (up to 30%). It was discovered that 8 is the kinetic product and is isomerized by 4-toluenesulfonic acid in hot benzene to the thermodynamically more stable 7. Under these conditions, ortho- and α-substituted aromatic ketones tend to produce more of 8, which can be attributed to steric hindrance encountered by the thiol as it attacks the ketone. Ketalizations of 1-aryl-2-(1H-imidazol-1-yl)-1- as well as 1-aryl-2-(1,H-1,2,4-triazol-1-yl)-1-ethanones by 1 fail under these conditions, even after 24 hours of reflux in toluene. However, 1-(4-chlorophenyl)-3-(1H-imidazol-1-yl)-1-propanone and 1-(4-bromophenyl)-4-(1H-imidazol-1-yl)-1-butanone are ketalized by 1 as expected. Interestingly, the reaction of 2-bromo-4′-chloroace-tophenone with 1 produces 1-(4-chlorophenyl)-2,8-dioxa-6-thiabicyclo[3.2.1]octane. Characterization of all isomers and separation of some diastereomers is described. Nuclear Overhauser enhancement experiments are utilized to establish the stereochemistry of 1,3-oxathiolanes.

The reactions of 4-amino-2-phenylcycloheptimidazole with alkyl iodides and α-bromoketones gave respectively 1-alkyl- and 1-acetonyl- (or 1-phenacyl)-substituted cycloheptimidazol-4(1H)-ones, while the reactions with acyl chlorides gave 4-arylamino-2-phenylcycloheptimidazoles. On the other hand, 2,4-diaminocycloheptimidazole were benzoylated with benzoyl chloride on the amino group at the 2- and/or 4-position and reacted with α-haloketones to give tricyclic 2-substituted 9-aminocyclohept[d]imidazo[1,2-a]imidazoles.

A series of antiinflammatory agents, based on the structural integration of fentiazac and lonazolac, was synthesized.

3-Aryl-4-amino-δ2-1,2,4-oxadiazolines 3 and their N-chloroacetyl derivatives 4, upon treatment with chloroacetic anhydride in refluxing toluene, afford 2-chloromethyl-5-aryl-1,3,4-oxadiazoles 5, suggesting the conversion sequence 3 → 4 → 5. The generality of the new ring transformation 4 → 5 is supported similar conversion of other 4-(acylamino)-1,2,4-oxadiazolines 8 to 1,3,4-oxadiazoles 9.

Reaction of 1-(3-bromo-2-oxopropyl)pyridazin-6-ones 1 and 2 with sodium azide at room temperature gave the corresponding 1-(3-azido-2-oxopropyl)pyridazin-6-ones 3 and 4, whereas reaction of 1-(1-bromo-2-oxo-propyl)pyridazin-6-ones 5 and 6 with excess sodium azide afforded 4-azido-5-chloropyridazin-6-one 7 and 4,5-diazido-3-nitropyridazin-6-one 8 by dealkylation. Some 1-(2-hydroxypropyl)pyridazin-6-ones 9, 10, 11 were synthesized from the corresponding 1-(2-oxopropyl) derivatives 1, 2, 3. 4,5-Dichloro-1-(2,3-dihydroxypropyl)-pyridazin-6-one 13 was also prepared from compound 9 via the corresponding 2,3-epoxypropyl derivative 12. Treatment of compound 5 with thiourea gave 4,5-dichloro-1-(2-amino-4-methylthiazol-5-yl)pyridazin-6-one 14. Reaction of compounds 1 and 2 with thiourea at 20° afforded the corresponding 3-formamidinylthio-2-oxo-propyl derivatives 15 and 16, whereas treatment of compound 1 with thiourea at 45° gave 4,5-dichloro-1-[(2-aminothiazol-5-yl)methyl]pyridazin-6-one 17. Compound 17 was also prepared from compound 15 by refluxing in ethanol.

Starting from cholesterol the three possible stereoisomeric 1,4-benzodioxanes 24, 31, 32 and a series of analogues with 2βH,3βH configuration (25–27, 29, 30) have been synthesized. The α band of the 1,4-benzodioxane chrompohore has been unequivocally identified in the CD spectra between 325–300 nm. For its Cotton effect the same helicity rule is valid as for homochirally analogous tetralins: the P/M helicity of the heteroring leads to a positive/negative CD within the α-band. The (2′R,3′R) configuration of 6 has been established by a comparison of its CD data with those of 39 and with the help of the above-mentioned helicity rule. This allows the assignement of the (2S,2′R,3′R) configuration of (−)-silandrin (3).

The intramolecular cyclizations of ω-haloenolate anions, −CαH2C(O)(CH2)n−3CωH2X with X = F, Cl and Br and n = 3–7, were investigated by the AM1 method. In most cases, cycloketone formation proceeds more favourably than cycloether formation, as predicted by the HSAB principle. The reactivity increases in the order X = F < Br < Cl for both processes, and for cycloether formation it is in the order n = 3 < 4 < 7 < 6 < 5 for all X but the relative order for n = 5 and 6 reverses in favour of n = 6 for cycloketone formation with X = Cl and Br. The softness of the acid centre, Cω, decreases for a harder X( = F) whereas it increases for a softer X( = Br). Thus the reactivity order with respect to X suggests that the softness of the base centres O and Cα belongs to the borderline class. The transition state (TS) structures indicate that the BEP principle is obeyed in all cases, and a less reactive process has a more product-like TS.