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We report the synthesis of 9-CD3-9-cis-retinal via a six-step procedure from β-ionone. The steps involve an initial deuteration of the methyl ketone of β-ionone followed by two consecutive Horner-Wadsworth-Emmons (HWE) coupling reactions and their corresponding DIBAL reductions. A final oxidation of the allylic alcohol of the retinol leads to the target compound. This deuterium labeled retinoid is an important cofactor for studying protein-retinoid interactions in isorhodopsin.

Plane tree belongs to Platanaceae family. There is a widespread belief that Platanus orientalis leaves (POLs) have beneficial effects on joint disorders. Therefore, many people consume POLs as tea. To our knowledge, as there is no study on volatile compounds (VCs) of POLs, we objected to determine the VCs in POLs obtained from Platanus orientalis trees grown in Hatay province, Turkey. The VCs were extracted using solid phase micro-extraction (SPME) and analyzed by gas chromatography-mass spectrometry (GC-MS). A total of 140 VCs were found in POLs. Aldehydes, alcohols, ketones, terpenes and alkenes were determined in POLs as major VCs groups, which accounted for 32.40 %, 23.51 %, 18.08 %, 10.24 % and 4.82 % of total VCs identified, respectively. Trans, trans-2,4-heptadienal (6.62 %), nonanal (6.46 %), benzaldehyde (6.42 %), cis-3-hexen-1-ol (6.32 %), benzenemethanol (6.13 %) were the most abundant VCs identified in POLs. Trans-2-hexenal (3.46 %), 3-phenyl-2-butanone (2.87 %), trans-3,5-dimethyl-1,6-octadiene (2.80 %), 6-methyl-5-hepten-2-one (2.56 %), octan-1-ol (2.43 %), trans-geranyl acetone (2.17 %), trans-4,8-dimethyl-1,3,7-nonatriene (1.98 %), phenyl methyl ketone (1.69 %), 6-methyl-3,5-heptadiene-2-one (1.57 %) were the second most plentiful compounds found in POLs. 11H-dibenzo[b,e][1,4]diazepin-11-one,5,10-dihydro-5-[3-(methylamino)propyl] (1.38 %), benzeneethanol (1.36 %) and β-ionone (1.02 %) were found as the third most abundant VCs. The above-mentioned VCs were accounted for about 57 % of total VCs identified in POLs. The remaining VCs were below 1.00 % that is, found at trace levels. According to the VCs profiles of POL, its beneficial effects on health may be due to aldehydes, alcohols, ketones and terpenes., Planetree belongs to Platanaceae family. There is a widespread belief that Platanus orientalis leaves (POLs) have beneficialeffects on joint disorders. Therefore, many people consume POLs as tea. To our knowledge,as there is no study on volatile compounds (VCs) of POLs, we objected to determinethe VCs in POLs obtained from Platanus orientalistrees grown in Hatay province, Turkey. The VCs were extracted using solid phasemicro-extraction (SPME) and analyzed by gas chromatography-mass spectrometry (GC-MS).A total of 140 VCs were found in POLs. Aldehydes, alcohols, ketones, terpenes andalkenes were determined in POLs as major VCs groups, which accounted for 32.40 %,23.51 %, 18.08 %, 10.24 % and 4.82 % of total VCs identified, respectively. Trans, trans-2,4-heptadienal (6.62 %), nonanal (6.46 %), benzaldehyde (6.42%), cis-3-hexen-1-ol (6.32 %), benzenemethanol(6.13 %) were the most abundant VCs identified in POLs. Trans-2-hexenal (3.46 %), 3-phenyl-2-butanone (2.87 %), trans-3,5-dimethyl-1,6-octadiene (2.80 %),6-methyl-5-hepten-2-one (2.56 %), octan-1-ol (2.43 %), trans-geranyl acetone (2.17 %), trans-4,8-dimethyl-1,3,7-nonatriene(1.98 %), phenyl methyl ketone (1.69 %), 6-methyl-3,5-heptadiene-2-one (1.57 %)were the second most plentiful compounds found in POLs. 11H-dibenzo[b,e][1,4]diazepin-11-one,5,10-dihydro-5-[3-(methylamino)propyl](1.38 %), benzeneethanol (1.36 %) and β-ionone (1.02 %) were found as the thirdmost abundant VCs. The above-mentioned VCs were accounted for about 57 % of totalVCs identified in POLs. The remaining VCs were below 1.00 % that is, found at tracelevels. According to the VCs profiles of POL, its beneficial effects on health maybe due to aldehydes, alcohols, ketones and terpenes.

Wacker-type reactions of terminal alkenes mainly lead to methyl ketones rather than aldehydes. The selective formation of aldehydes usually requires alkenes containing a suitable coordinating fragment. A few procedures however provide fair to high aldehyde/methyl ketone ratios in the absence of a directing group. This review, which is focused on the formation of aldehydes, summarizes the methods reported since 2007 and, with personal comments, the mechanisms and intermediates proposed to rationalize the regioselectivity.

Iodine-catalyzed the reaction of substituted methyl ketone N-tosylhydrazones with elemental sulfur has been developed. The cyclizations of the ester-substituted N-tosylhydrazone substrates proceeded smoothly under optimal reaction conditions, and the corresponding products 4-alkyl-1, 2, 3-thiadiazoles are obtained. For the reaction of 4-arylbutan-2-one of N-tosylhydrazone substrates, (E)-4-styryl-1, 2, 3-thiadiazole derivatives were obtained with high selectivity through the control of reaction conditions. In addition, gram-scale synthesis and further transformation of the product were also investigated.

Reactions of Cp2TiMe2, with the ester derivatives of organometallic sandwich compounds (ɳ5-RC5H4)Fe(ɳ5-C5H5) and (ɳ5-RC5H4)Co(ɳ4-C4Ph4) (R=ester groups) gave products having R=C(CH2)Me, instead of the expected vinyl ethers indicating conversion of the ester units by Cp2TiMe2 to methyl ketones followed by methylenation. A reaction of Cp2TiMe2 with the diester (ɳ5-RC5H4)Co(ɳ4-C4Ph3R)(R C(O)OMe) also gave similar results. The study has also been successfully extended to metal sandwich derived amides, thio and seleno esters. By controlling the amount of Cp2TiMe2, the reactions were also stopped at the methyl ketone stage and the methyl ketones were isolated in good yields and characterized. The method provides an easy and direct access to convert organometallic sandwich derived esters and related compounds to 1-methylvinyl derived products.

The development of tandem radical Csp3-H functionalization/cycloaddition of methyl ketone, tert-butyl nitrite, and maleimide has been reported herein. A variety of pyrrolo[3,4-d]isoxazolines have been successfully synthesized under metal-free conditions with excellent functional group compatibility. X-ray crystallography of the pyrrolo[3,4-d]isoxazoline was obtained and the reaction mechanism was proposed.

vi CHAPTER ONE: GENERAL INTRODUCTION 1 I. Dependence on Petroleum Products 1 II. Alternative Fuels from Biorenewable Sources 1 III. Alternative Chemicals from Biorenewable Sources 3 CHAPTER TWO: LITERATURE REVIEW 5 I. Fatty Acid Production Methods 6 II. Methyl Ketone Production 14 CHAPTER THREE: FERMENTATIVE PRODUCTION OF SHORT-CHAIN 16 FATTY ACIDS IN ESCHERICHIA COLI I. Abstract 16 I

A reliable three-step synthesis of ortho-substituted 4-pyrazolyl-2-ethylamines starting from a pyrazole methyl ketone and N-tert-butanesulfinylamine is described. Strongly dehydrating conditions were required to form the N-tert-butanesulfinyl ketimines, but these intermediates were stable to aqueous work-up and chromatography. Reduction of N-tert-butanesulfinyl ketimines with L-selectride®, or Super-hydride®, in THF afforded excellent yields and diastereoselectivities of the sulfinamides, which were converted into chiral amines with methanolic HCl. The 4-pyrazolyl-2-ethylamines from these investigations are attractive building blocks for medicinal chemists, as they exhibit low molecular weight, and low calculated octanol-water partition coefficient (c Log P values), while disrupting planarity with three-dimensional character. For example, the amine products were utilized in structure-activity studies of the human transient receptor potential vanilloid 1 (TRPV1/VR1).

The tumorigenic activity of upregulated Mcl-1 is manifested by binding the BH3 α-helical death domains of opposing Bcl-2 family members, neutralizing them and preventing apoptosis. Accordingly, the development of Mcl-1 inhibitors largely focuses on synthetic BH3 mimicry. The condensation of α-pyridinium methyl ketone salts and α,β-unsaturated carbonyl compounds in the presence of a source of ammonia, or the Krohnke pyridine synthesis, is a simple approach to afford highly functionalized pyridines. We adapted this chemistry to rapidly generate low-micromolar inhibitors of Mcl-1 wherein the 2,4,6-substituents were predicted to mimic the i, i + 2 and i + 7 side chains of the BH3 α-helix.

n . The latter compounds were supposedly formed by free-radical reactions, followed by spontaneous benzilic acid rearrangement and esterification. Furthermore, extraction of M. perennis with aqueous Me2CO produced an aldol condensation product, the known alkaloid speranskatine A (9a), which was identified by NMR after chromatographic purification. In a similar manner, a CH2 homolog of speranskatine A (10a) was obtained as a novel compound when ethyl methyl ketone (¼ butan-2-one; EtCOMe) instead of Me2CO was used for extraction. Consequently, 1 easily undergoes artefact formation upon extraction of plant material with polar or slightly polar solvents.

An I2–DMSO promoted novel and efficient method is described for the synthesis of isatins from 2-aminoaryl methyl ketone. A series of alkyl or aryl isatin derivatives were successfully synthesized under the optimized reaction conditions.

The chemical composition of the essential oil of Perilla frutescens (L.) Britt. aerial parts and its insecticidal activity against Tribolium castaneum and Lasioderma serricorne were investigated. The essential oil of P. frutescens was obtained by hydrodistillation and a total of 34 components in the essential oil were identified with GC–MS. It was found that the main compounds included 2-furyl methyl ketone (71.83 %), decahydro-1-methyl-2-methylene-naphthalene (10.47 %), limonene (5.16 %) and caryophyllene (1.66 %). With a further isolation, the two active constituents were obtained from the essential oil and identified as 2-furyl methyl ketone, limonene. In the progress of assay, it showed that the essential oil and 2-furyl methyl ketone exhibited stronger contact and fumigant activities against the two stored product insects than limonene. Moreover, the essential oil and its constituents exhibited the comparable repellency against the two stored product insects, relative to the positive control, DEET. The results indicate that the essential oil of P. frutescens aerial parts and its isolated compounds have potential for development into natural insecticides or fumigants as well as repellents for control of insects in stored grains.

A series of β-disubstituted N-sulfinyl β-amino isoxazolyl ketones has been prepared by addition of tert-butanesulfinyl ketimines with the n-BuLi-generated enolates of isoxazolyl methyl ketones.

A novel mode of achieving site selectivity between C-2 and C-4 positions in the indole framework by altering the property of the ketone directing group is disclosed. Methyl ketone, as directing group, furnishes exclusively C-2 alkenylated product, whereas trifluoromethyl ketone changes the selectivity to C-4, indicating that the electronic nature of the directing group controls the unusual choice between a 5-membered and a 6-membered metallacycle. The screening of other carbonyl-derived directing groups reveals that strong and weak directing groups exhibit opposite selectivity. Experimental controls and deuteration experiments lend support to the proposed mechanism.

A formal asymmetric synthesis of the marine natural product apratoxin D, a highly potent inhibitor of H-460 human lung cancer cell growth (IC 50 value of 2.6 nM), is described. The key feature of the synthesis is an advanced-stage asymmetric ACC α,α-bisalkylation of a chiral nonracemic methyl ketone to provide access to an advanced intermediate as a single diastereomer that has previously been advanced to apratoxin D.

A highly stereocontrolled total synthesis of the cytotoxic marine macrolide aplyronine C is described. The route exploits aldol methodology to install the requisite stereochemistry and features a crucial boron-mediated aldol coupling of an N-vinylformamide-bearing methyl ketone with a macrocyclic aldehyde to introduce the full side chain. The synthesis of two novel C21–C34 side chain analogs is also reported.

A new method for the tunable synthesis of 1,4-enedione directly from aromatic methyl ketone is described. This tandem reaction enables the construction of symmetric and unsymmetric 1,4-enediones with complete E-selectivity. Moreover, the resulting E-1,4-enedione could be transformed into a Z-isomer by irradiation with 23 W of white light.

A highly efficient method for the synthesis of 1,2,3-triaroylindolizines has been established from readily available methyl ketones and pyridines in the presence of iodine. This reaction also examplified the self-division of labor strategy in convergent domino synthesis.

Densities, ρ, and viscosities, η, of binary mixtures of 2-methyl-2-propanol with acetone (AC), ethyl methyl ketone (EMK) and acetophenone (AP), including those of the pure liquids, were measured over the entire composition range at 298.15, 303.15 and 308.15 K. From these experimental data, the excess molar volume $V_{\mathrm{m}}^{\mathrm{E}}$ , deviation in viscosity Δη, partial and apparent molar volumes ( $\overline{V}_{\mathrm{m},1}^{\,\circ }$ , $\overline{V}_{\mathrm{m},2}^{\,\circ }$ , $\overline{V}_{\phi ,1}^{\,\circ}$ and $\overline{V}_{\phi,2}^{\,\circ} $ ), and their excess values ( $\overline{V}_{\mathrm{m},1}^{\,\circ \mathrm{E}}$ , $\overline{V}_{\mathrm{m,2}}^{\,\circ \mathrm{ E}}$ , $\overline {V}_{\phi \mathrm{,1}}^{\,\circ \mathrm{ E}}$ and $\overline{V}_{\phi \mathrm{,2}}^{\,\circ \mathrm{ E}}$ ) of the components at infinite dilution were calculated. The interaction between the component molecules follows the order of AP > AC > EMK.

Edessa meditabunda is a secondary pest within the piercing-sucking stink bug complex that attacks soybean crops in Brazil. The behavioral responses of males and females to aeration extracts from conspecifics suggested the presence of a male-produced sex pheromone. Gas chromatographic (GC) analysis of male and female aeration extracts revealed the presence of two male-specific compounds in a ratio of 92:8. Gas chromatographic -electroantennographic detection (GC-EAD) assays indicated that the major component is bioactive for females, supporting the behavioral data. Analysis of the mass and infrared spectra of the male-specific compounds suggested that they were both methyl-branched long-chain methyl esters. On the basis of the mass spectra of the respective hydrocarbons obtained by micro derivatizations, the structures of these methyl esters were proposed to be methyl 4,8,12-trimethylpentadecanoate (major) and methyl 4,8,12-trimethyltetradecanoate (minor). An 11 step synthetic route that was based on a sequence of Grignard reactions, starting from cyclopropyl methyl ketone, was developed to obtain synthetic standards with a 7.9 % overall yield for the major compound and a 9.9 % yield for the minor. The synthetic standards co-eluted with the natural pheromones on three different GC stationary phases. Y-tube olfactometer assays showed that the synthetic standards, including the major compound alone and a mixture of the major and minor compounds in the proportion found in natural extracts, were strongly attractive to females.

Geometric parameters, vibrational frequencies, conformer energy difference, and barriers to internal rotation for the cyclopropyl methyl ketone (CPMK, c -С 3 H 5 C(O)CH 3 ) molecule in the ground electronic state were obtained by performing MP2, MP4(SDQ), CCSD, and CCSD(T) calculations and VFPA. Ab initio one-dimensional and two-dimensional potential functions corresponding to the rotations of the acetyl C(O)CH 3 and methyl CH 3 tops were used to calculate torsion transition energies by the variational method. Two torsion motions were found to be strongly coupled in the region of the near-trans conformer of CPMK.

The reactions of 5-pyrrolyl-pyrimidinyloxyacetaldehyde or methyl ketone with primary amines yielded hydroxymethylpyrrolopteridine derivatives via a cascade of iminium cyclization and O–N Smiles rearrangement. The present cascade exhibited a different profile compared to the previously reported ones, which consisted of N–N Smiles rearrangement. Lewis acid (TiCl4) under carefully controlled conditions was employed to suppress the competing formation of imine dimers to give the desired heterocycles. A plausible mechanism involving the iminium cyclization and Smiles rearrangement is proposed. This methodology has been used to generate a series of 6-hydroxymethylpyrrolo[1,2-f]pteridine derivatives with potential biological activities.

A new method for the construction of the eight-membered carbocyclic ring in the taxane skeleton is described. The palladium-catalyzed intramolecular α-alkenylation of a methyl ketone effectively constructed the eight-membered carbocyclic ring in the taxol model compound. To the best of our knowledge, this reaction is the first example of forming an eight-membered carbocyclic ring by the palladium-catalyzed intramolecular α-alkenylation of a ketone.

Synthesis of the C1-C23 fragment in spirastrellolide A is described, featuring a cyclic acetal-tethered RCM for stereoselective constructions of spiroketal, and a 1,3- anti aldol involving methyl ketone enolate and Mukaiyama conditions.

The application of microwave heating to a silica-assisted solution-phase synthesis technique has been utilized to develop a rapid and efficient two-step protocol for the preparation of pyrazoles from aryl methyl ketone and aryl hydrazine monomers.

A facile two-step synthesis of natural germination inhibitor 5-butyl-3-oxo-2,3-dihydrofuran-2-yl-acetic acid [(+)-erigeronic acid A, 1] has been described via highly regioselective ring opening of (R)-acetoxysuccinic anhydride with the primary enolate of butyl methyl ketone, followed by an enzymatic hydrolysis and an in situ dehydrative cyclization pathway with 77% overall yield. On the basis of the present chemoenzymatic approach, (R)-configuration has been assigned to the C-2 chiral centre of the natural erigeronic acid.

Amine boranes bearing hydrophobic substituents were used to reduce aryl ketones in competition with a methyl ketone. Their high stability in protic solvents combined with their ease of preparation made amine boranes useful compounds in the study of hydrophobically directed selective reductions. Several characteristics of the reducing agent were found to be important in determining the reaction selectivity, including available hydrocarbon surface area, degree of fluorination, and proximity of the hydrophobic group to the active hydrides.

13C1-pinonaldehyde is prepared in seven steps from cis-pinonic acid. In the key sequence, the introduction of labeled carbon is accomplished by Lieben degradation of a methyl ketone followed by treatment of the resultant carboxylic acid with 13C-methyl lithium. Copyright © 2005 John Wiley & Sons, Ltd.

[reaction: see text] An efficient synthesis of the C(11)-C(29) fragment 31 of amphidinolide F has been accomplished via a diastereoselective [3 + 2]-annulation reaction of allylsilane 5 and ethyl glyoxylate to prepare the key tetrahydrofuran 15 and a highly stereoselective methyl ketone aldol reaction to generate the C(11)-C(16) segment.

In sausage, Staphylococcus carnosus increases the levels of methyl ketones which could arise from incomplete β-oxidation of fatty acids followed by a decarboxylation. The objective of this work was to characterize the β-decarboxylase activities in cell-free extract. By using different substrates, at least two kinds of β-decarboxylase activities were shown: an acetoacetate-like and an oxaloacetate-like. The first one leads to the production of ketones from ethylbutyryl acetate or acetoacetic acid. The activity was optimal at pH 6.0, stimulated by pyridoxal phosphate but ethylenediamine tetraacetic acid (EDTA), NaCl, iodoacetate and curing additives were inhibitory. The second decarboxylase activity leads to the production of pyruvic acid from oxaloacetic acid. This activity was optimal at pH 5.0 and stimulated by divalent ions and biotin. Fil: Fadda, Silvina G.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina. Institut National de la Recherche Agronomique; Francia Fil: Leroy Sétrin, Sabine. Institut National de la Recherche Agronomique; Francia Fil: Talon, Régine. Institut National de la Recherche Agronomique; Francia

[structure: see text] Non-aldol aldol rearrangement of the epoxy silyl ether 13b afforded the expected anti methyl ketone 14, while the diastereomeric epoxy silyl ether 13a afforded the syn methyl ketone 8b via an unprecedented syn hydride migration. Calculations suggest that this unusual reaction proceeds via the carbocation, which cannot easily rotate due to steric hindrance.

The reaction of (2,4,6)-tri-isopropylphenyl methyl ketone with tri-phenylaluminium was investigated. [Ph 2 AlO(2,4,6-tri- i Pr-C 6 H 2 )CCH 2 ] 2 was found to be formed exclusively. The title compound has been characterised by NMR and its crystal structure determined by X-ray diffraction study.

The addition of triphenylphosphine to methyl propiolate, ethyl propiolate, or ethynyl methyl ketone in the presence of a strong NH-acid, such as 5-nitro-2,4-dihydro-3 H -1,2,4-triazol-3-one, leads to stable 1,6-diionic organophosphorus compounds in excellent yields.

Chiral trichlorosilyl enolates bearing a remote stereogenic center were employed in the phosphoramide-catalyzed aldol reaction. The additions of the methyl ketone enolates proceeded with only moderate diastereoselectivities. The addition of the Z-enolate to various aldehydes selectively produced the syn relative diastereomers. In both cases, the effect of the beta-silyloxy stereogenic center was modest, and the internal diastereoselection was mainly controlled by the catalyst. [reaction: see text]

Staphylococcus carnosus strain 833, inoculated into sausage, increased the levels of methyl ketones which contributed to the cured aroma. These ketones were predicted to arise from incomplete β-oxidation followed by a decarboxylation. To check this hypothesis, we measured the β-decarboxylase activity in resting cells of S. carnosus grown in complex or in synthetic medium, using as substrate a β-ketoacid, which can be an intermediate of the β-oxidation pathway. This activity was present throughout the growth period. The enzyme appeared to be constitutive because no induction was observed. High aeration, a pH of 5 and the presence of nitrate promoted the production of methyl ketones. Fil: Fadda, Silvina G.. Institut National de la Recherche Agronomique; Francia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina Fil: Lebert, André. Institut National de la Recherche Agronomique; Francia Fil: Leroy Sètrin, Sabine. Institut National de la Recherche Agronomique; Francia Fil: Talon, Régine. Institut National de la Recherche Agronomique; Francia

The Baeyer–Villiger reaction of a series of compounds related to an intermediate in our synthesis of (+)-dactylol showed a pattern of regioselectivity which could be varied to a small extent as a function of substitution on the precursor. A very unusual Baeyer–Villiger reaction of a methyl ketone resulted in a product from apparent insertion of an oxygen atom into between the carbonyl carbon and the methyl group of the acetyl functionality.

We report an improved procedure for the synthesis of phenyl glyoxal and a series of para-substituted aryl glyoxals by microwave-assisted selenium dioxide oxidation. The reaction time has been reduced from several hours to three minutes for activated aryl methyl ketone substrates and 18 min for deactivated substrates, with all reactions affording quantitative conversion into the corresponding aryl glyoxals.

A new approach for tethering of bioactive molecules via arginine is proposed and validated on collagen 2D matrices. The method involves the introduction of a methyl ketone on arginine side-chains, followed by reaction with model alkoxyamino derivatives. This journal is © the Partner Organisations 2014.

Secondary allylic alcohols with 10 mol% of Grubbs catalyst in refluxing toluene/1,2-dichloroethane undergo isomerisation to ethyl ketones whereas with 100 mol% of Grubbs catalyst at room temperature, a net fragmentation reaction with the loss of a carbon atom occurs, to provide a methyl ketone. Probable mechanisms are described.

Two spirobicyclic sesquiterpenoids, (−)-erythrodiene (1) and (+)-7-epispirojatamol (30), were synthesized in enantiomerically pure form via an intramolecular allylzincation process. The allylzinc species were formed in the presence of Et2Zn via transmetallation of a catalytically generated allylpalladium intermediate. Several Pd catalysts were tested for this transformation, and [Pd(OAc)2]/Bu3P (1 equiv.) was found to be, by far, the most effective. Whereas the preparation of 1 involved allylzincation of a tethered terminal olefin, 30 was formed via a novel intramolecular allyl zincation of a methyl ketone. Both reactions showed the same stereochemical preference, yielding the spirobicyclic products in 95 : 5 and 4 : 1 diastereoisomer ratios, respectively.

[structure: see text]. The tetracyclic ketal 24, a suitable intermediate for the synthesis of antitumor pentacyclic quassinoids, has been efficiently prepared from communic acids (5a-c), via methyl ketone 9. The synthetic sequence from 9 to 24 consists of 15 steps in 12% overall yield.

A highly stereoselective synthesis of the C(13)–C(25) fragment of scytophycin C is described, along with stereochemical studies of the key fragment assembly methyl ketone aldol reaction.

[formula: see text] A highly diastereoselective synthesis of 3, corresponding to the C(5)-C(21) segment of tedanolide, has been accomplished by a route utilizing the aldol reaction of aldehyde 4 and the beta,gamma-unsaturated methyl ketone 5.

1-(6′-Methoxy-2′-naphthyl)ethanol is asymmetrically carbonylated to the methyl ester of ( S )-naproxen in a PdCl 2 CuCl 2 -DDPPI (DDPPI: 1,4:3,6-dianhydro-2,5-dideoxy-2,5-bis(diphenylphosphino)- L -iditol) catalytic system with a chemical yield of 90% and an optical yield of 81% e.e.. The reaction was carried out in ethyl methyl ketone under 100°C and 8 MPa of CO for 24–48h.

The addition of the metalated 1,4-dimethoxybenzenes 17a-c to the methyl ketone 14 was investigated in connection with the construction of the C-glycosidic part of nogalamycin. In most reactions, a selectivity towards the undesired (S)-isomer 16a was observed. However, the reaction of the lithiated aromate 17c with 14 at low temperatures in THF favored the formation of the desired (R)-alcohol 15a (15a:16a = 4.8:1) in accordance with the chelate model A. The selectivity was considerably enhanced in the addition of the more hindered lithiated naphthalene 18 yielding the (R)-isomer 15b exclusively. Reduction of 15b afforded the dimethylamino compound 19b, a direct precursor of the CDEF-ring system of nogalamycin.

The tricyclic derrivative ( 10d ) has been prepared by intramolecular Reformatsky addition of α-bromopropionate ( 8b ) in the presence of diethylaluminum chloride and activated Zn. Transformation of ( 10d ) into the tricyclic methyl ketone ( 12a ) was accomplished by dehydration followed by oxidation under Wacker conditions with 75% overall yield.

Wacker oxidation reaction of terminal olefins bearing one or two fluorine atoms at a homoallylic position led to a ratio aldehyde/methyl ketone much higher than that observed with their non-fluorinated analogues. This regioselectivity can be ascribed to a specific interaction between fluorine atoms and palladium, or to a peculiar influence of the halogens on the double bond.

Several substituted methyl ketone derivatives of tripeptides with a C-terminal arginyl residue were synthesized as active site inhibitors of human α-thrombin. The most active compound among this series was the pyridinium methyl ketone D-Cha-Pro-Arg-PMK, which was characterized as a slow-binding inhibitor with a Ki of 0.19 nM.

Two coupling strategies for (−)-pre-swinholide A were devised based on the analysis in Scheme 1. In the first route, a boron-mediated aldol reaction between the ethyl ketone 19 and the aldehyde 3 was used to construct the C15-C16 bond with moderate diastereoselectivity. In the second route, a Mukaiyama aldol reaction between the methyl ketone 54 and the aldehyde 4 introduced the C18-C19 bond with complete stereocontrol.