The Synthesis of Olefins from Carbonyl Compounds and Phosphonic Acid Bisamides

Corey, E. J.; Kwiatkowski, G. T.

doi:10.1021/ja00975a055

Cited by 56 publications

(21 citation statements)

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“…A 15-mL 3-necked flask containing 3.7 mL of THF and diethyl methylphosphonate (0.40mL, 2.7 mmol) under a dry, nitrogen atmosphere was placed into a -78 OC bath. After cooling, 2.5 M n-butyllithium (1 .O mL, 2.5 mmol) was added dropwise with stirring (Corey & Kwiatkowski, 1966). The solution was allowed to stir for 5 min at -78 OC, and then it was transferred via syringe to a 25-mL three-neck flask containing 7 (597 mg, 1 mmol) in 3.0 mL of THF under a dry, nitrogen atmosphere at -78 OC.…”

Section: Experimentalproceduresmentioning

confidence: 99%

A transition state in pieces: major contributions of entropic effects to ligand binding by adenosine deaminase

Kati

Acheson²,

Wolfenden³

1992

Biochemistry

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Nebularine undergoes hydration at the active site of adenosine deaminase, in a reaction analogous to a partial reaction in the displacement of ammonia from adenosine by water, to generate an inhibitory complex that captures much of the binding affinity expected of an ideal transition-state analogue. Enzyme affinities of several compounds related to nebularine 1,6-hydrate, and to its stable analog 2'-deoxycoformycin, were compared in an effort to identify the structural origins of strong binding. Binding of the stable transition-state analog inhibitor 2'-deoxycoformycin was rendered 9.8 kcal/mol less favorable by removal of substituent ribose, 9.7 kcal/mol less favorable by inversion of the 8-hydroxyl substituent of the diazepine ring, and 10.0 kcal/mol less favorable by removal of atoms 4-6 of the diazepine ring. Binding of the unstable transition-state analog nebularine hydrate was rendered at least 9.9 kcal/mol less favorable by removal of the 6-hydroxyl group and 10.2 kcal/mol less favorable by removal of atoms 1-3 of the pyrimidine ring. In each case, the enzyme exhibited only modest affinity (Kd greater than or equal to 10(-2) M) for the "missing piece", indicating that incorporation of 2 binding determinants within a single molecule permits an additional 7-12 kcal/mol of intrinsic binding energy to be manifested as observed binding energy. These results are consistent with earlier indications that adenosine deaminase may use 10.5 kcal/mol of the intrinsic free energy of binding of the two substrates to place them in positions appropriate for reaction at the active site, overcoming the unfavorable entropy change of -35 eu for the equilibrium of 1,6-hydration of purine ribonucleoside and reducing the equilibrium constant for attainment of the transition state in deamination of adenosine. Thus, adenosine deaminase may achieve up to 8 orders of magnitude of its catalytic power by converting the nonenzymatic, bimolecular, hydration reaction to a monomolecular reaction at its active site. Several new 6-substituted 1,6-dihydropurine ribonucleosides, prepared by photoaddition of formate and by low-temperature addition of organolithium reagents to a derivative of purine ribonucleoside, exhibited Ki values of 9-1400 microM against adenosine deaminase, in accord with the active site's considerable tolerance of bulky leaving groups in substrates. Inhibition by one diastereomer of 6-carboxy-1,6-dihydropurine ribonucleoside was found to be time-dependent, progressing from a weakly bound to a more strongly bound complex.

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Section: Experimentalproceduresmentioning

confidence: 99%

A transition state in pieces: major contributions of entropic effects to ligand binding by adenosine deaminase

Kati

Acheson²,

Wolfenden³

1992

Biochemistry

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“…The organic extracts were washed with aqueous sodium hydroxide ( 1 ~) until the washings were colourless, washed with water, dried, and evaporated to give the title compound as an oil ( 9 6,6.54(1 H, s, ArH), 3.93 (3 H, s, OMe), 3.82 (3 H, s, OMe), 3.78 (3 H, s, OMe), and 2.22 (3 H, s, ArMe). 4-Chloro-1 -dibromomethyl-2,3,5-trimethoxybenzene (36).-N-Bromosuccinimide (1.22 g) was added to a solution of 4-chloro-2,3,5-trimethoxytoluene (35) (0.7 1 g) in carbon tetrachloride (40 ml) and the mixture was heated under reflux while being irradiated with a tungsten lamp for 1.5 h; it was then allowed to cool. The precipitated succinimide was removed and the solvent evaporated off.…”

Section: -Chloro-35-dimethoxytoluene-2-ol (34)mentioning

confidence: 99%

Synthesis of 2,3,5-trihydroxyphenylprop-1-ene and its 4-chloro-, 6-chloro-, and 4,6-dichloro- derivatives

Hill¹,

Macaulay²,

MacLachlan³

1987

J. Chem. Soc., Perkin Trans. 1

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“…Therefore, the preparation and reaction of these species possessing two α-alkyl substituents have been the subjects of little synthetic work. Only isopropylidene- and cycloalkylidene-phosphoranes and similar α-phosphoryl- and α-silyl-carbanions, whose substituents present minimal steric hindrance to the approaching carbonyl compound, are prepared and employed for carbonyl olefination. Although Aguero et al reported the olefination of carbonyls using tungsten−alkylidene complexes, only the cyclopentylidene complex was employed for the preparation of tetrasubstituted olefins .…”

Section: Introductionmentioning

confidence: 99%

Carbonyl Olefination by Means of a gem-Dichloride−Cp₂Ti[P(OEt)₃]₂ System

1998

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The preparation of highly substituted olefins by carbonyl olefination using a gem-dichloride-Cp(2)Ti[P(OEt)(3)](2) system was studied. The treatment of organotitanium species, formed by reaction with titanocene(II) species from gem-dichlorides having two alkyl substituents, with an aldehyde or ketone afforded tri- or tetrasubstituted olefins in good yields. Acyclic or cyclic trisubstituted vinyl ethers were also obtained by a similar reaction using carboxylic esters or lactones as carbonyl components.

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The Synthesis of Olefins from Carbonyl Compounds and Phosphonic Acid Bisamides

Cited by 56 publications

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A transition state in pieces: major contributions of entropic effects to ligand binding by adenosine deaminase

A transition state in pieces: major contributions of entropic effects to ligand binding by adenosine deaminase

Synthesis of 2,3,5-trihydroxyphenylprop-1-ene and its 4-chloro-, 6-chloro-, and 4,6-dichloro- derivatives

Carbonyl Olefination by Means of a gem-Dichloride−Cp₂Ti[P(OEt)₃]₂ System

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The Synthesis of Olefins from Carbonyl Compounds and Phosphonic Acid Bisamides

Cited by 56 publications

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A transition state in pieces: major contributions of entropic effects to ligand binding by adenosine deaminase

A transition state in pieces: major contributions of entropic effects to ligand binding by adenosine deaminase

Synthesis of 2,3,5-trihydroxyphenylprop-1-ene and its 4-chloro-, 6-chloro-, and 4,6-dichloro- derivatives

Carbonyl Olefination by Means of a gem-Dichloride−Cp2Ti[P(OEt)3]2 System

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Carbonyl Olefination by Means of a gem-Dichloride−Cp₂Ti[P(OEt)₃]₂ System