Synthesis methyl ketones

Ketone body synthesis occurs only in the mitochondrial matrix. The reactions responsible for the formation of ketone bodies are shown in Figure 24.28. The first reaction—the condensation of two molecules of acetyl-CoA to form acetoacetyl-CoA—is catalyzed by thiolase, which is also known as acetoacetyl-CoA thiolase or acetyl-CoA acetyltransferase. This is the same enzyme that carries out the thiolase reaction in /3-oxidation, but here it runs in reverse. The second reaction adds another molecule of acetyl-CoA to give (i-hydroxy-(i-methyl-glutaryl-CoA, commonly abbreviated HMG-CoA. These two mitochondrial matrix reactions are analogous to the first two steps in cholesterol biosynthesis, a cytosolic process, as we shall see in Chapter 25. HMG-CoA is converted to acetoacetate and acetyl-CoA by the action of HMG-CoA lyase in a mixed aldol-Claisen ester cleavage reaction. This reaction is mechanistically similar to the reverse of the citrate synthase reaction in the TCA cycle. A membrane-bound enzyme, /3-hydroxybutyrate dehydrogenase, then can reduce acetoacetate to /3-hydroxybutyrate. 

The ability of 1,2 (or l,6)-dihydropyridines to undergo a Diels-Alder reaction with dienophiles such as methyl vinyl ketone, methyl acrylate, and acrylonitrile has been utilized in the synthesis of polyfunctional isoquinuclidine as a key intermediate in the synthesis of aspidosperma- and iboga-type alkaloids (66JA3099). 

In the partial synthesis shown, there are two reagents, the a,P-unsaturated ketone methyl vinyl ketone and the 1,3-diketone 2-methylcyclohexa-1,3-dione. 

The first two reactions in the cholesterol synthetic pathway are siri lar to those in the pathway that produces ketone bodies (see Figure 16.22, p. 194). They result in the production of 3-hydroxy-3-methyl-glutaryl CoA (HMG CoA, Figure 18.3). First, two acetyl CtA molecules condense to form acetoacetyl CoA. Next, a third molecule of acetyl CoA is added, producing HMG CoA, a six-carbon compound. [Note Liver parenchymal cells contain two isoenzymes of HMG CoA synthase. The cytosolic enzyme participates in cholesterol synthesis, whereas the mitochondrial enzyme Urc tions in the pathway for ketone body synthesis.]... 

Problem 21.11 The aldol condensation of unsymmetrical ketones (methyl ethyl ketone, for example) is usually of little value in synthesis. Why do you think this is so ... 

Kerosene, purified, 24, 7 Ketene, 21, 13, 64 Ketene diethylacetal, 23, 45 Ketene, diethyl ketal, 23, 45 Ketene dimer, 21, 4, 64 Ketene lamp, 21, 65 Keto acid, 20, 2 -Ketoglutaric acid, 26, 42 Ketone, 2-Fluorenyl methyl, 28,3,63 Ketone, methyl 9-phenanthryl, 28,6 Ketone, methyl 2-thienyl, 28,1 Knoevenagel condensation, 23, 60 24, 92 25, 42, 51 27, 24 28, 24 Kolbc synthesis of an alkyl a,a>-dicar-boxylatc, 21, 48... 

Beilstein Handbook Reference) Aceto-cinnamone AI3-00944 Benzalaceton Benzalacetone Benzilidene acetone Benzilideneacetone Benzylidene-acetone BRN 0742046 3-Buten-2-one, 4-phenyl- CCRIS 5319 EINECS 204-555-1 FEMA No. 2881 Ketone, methyl styryl Methyl 2-phenylvinyl ketone Methyl styryl ketone Methyl (3-styryl ketone NSC 5605 4-Phenylbutenone 4-Phenyl-3-buten-2-one 2-Phenylvinyl methyl ketone Styryl methyl ketone. Used in organic synthesis and perfumery used as a fixative and in flavors. Solid mp = 41.5°. Lancaster Synthesis Co. Penta Mfg. Raschig GmbH. 

Hydroxyphenyl methyl ketone Methyl p-hydroxyphenyl ketone NSC 3698 p-Oxyacetophenone Phenol, p-acetyl- Piceol USAF KF-15. Used in organic synthesis. Needles mp = 109.5° bp3 = 147-148° d 5 = 1.1090 Pimo 220, 275 nm (MeOH) slightly soluble In H2O, DMSO, very soluble in EtOH, Et20. Greeff R.W. i Co. Hoechst Celanese Janssen Chimica Lancaster Synthesis Co,... 

Beilstein Handbook Reference) AI3-03075 BRN 1209331 t-Butyl methyl ketone tert-Butyl methyl ketone EINECS 200-9204 HSDB 5210 Ketone, t-butyl methyl Ketone, tert-butyl methyl Methyl t-butyl ketone Methyl tert-butyl ketone NSC 935 Pinacolin Pinacoline Pinacolone Pinakolin. Used in chemical synthesis, manufacture. Liquid mp = -52.5° bp = 106.1° d = 0.7229 slightly soluble in H2O (2.5 g/100 ml), more soluble in organic solvents LD50 (rat orl) = 610 mg/kg. Lancaster Synthesis Co. Mallinckrodt inc. Sigma-Aldrich Fine Chem. 

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