Claisen condensation decarboxylation following

Step 5 of Figure 29.5 Condensation The key carbon-carbon bond-forming reaction that builds the fatty-acid chain occurs in step 5. This step is simply a Claisen condensation between acetyl synthase as the electrophilic acceptor and malonyl ACP as the nucleophilic donor. The mechanism of the condensation is thought to involve decarboxylation of malonyl ACP to give an enolate ion, followed by immediate addition of the enolate ion to the carbonyl group of acetyl... 

The low-energy tandem mass spectra of the deprotonated molecular ions of acylglycerol contain a type of ion whose formal mass-based composition corresponds to a ketone obtained by the combination of two fatty acid chains with a carbonyl group, minus a proton. The ketone contains mainly the chains of the central fatty acid combined with one of the two external fatty acids, even if the ketone containing the two external fatty acids is present with a much weaker intensity. The formation of these ions may be explained by an internal Claisen condensation followed by a fragmentation induced by a nucleophile substitution and then by a decarboxylation, as shown in Figure 8.64. 

This synthesis uses a Claisen condensation, followed by a p-keto ester decarboxylation. 

Which of the following steps doesn t occur in the synthesis of isopentenyl diphosphate (a) Claisen condensation (b) oxidation (c) aldol condensation (d) decarboxylation... 

The alkylation of p-keto ester enolates followed by decarboxylation affords substituted ketones (acetoacetic ester synthesis). The ester group acts as a temporary activating group. Retro-Claisen condensation can be a serious problem during hydrolysis of the ester, particularly in basic solution if the product has no protons between the carbonyl groups. In these cases, the hydrolysis should be carried out under acidic conditions or using one of the methods of decarbalkoxylation described in the next section. 

Intramolecular Claisen condensation of triester (119) gave the ketopyrrolizine (120), which, following saponification and decarboxylation was reduced to (121) or (122). Dihydropyrrolizines such as (121) are metabolites of highly toxic pyrrolizidine alkaloids <71HCA449>. 

Recently Y. Tanabe published a one-pot synthesis starting from methyl dec-9-enoate. [187,188] Key steps are a Lewis acid-catalysed Claisen condensation and a ring-closing metathesis. It is noteworthy that the metathesis proceeds in presence of a titanium enolate complex. Decarboxylation follows spontaneously and gives the product in 48 % yield. 

Recall from Section 14.3C that the hydrolysis of an ester in aqueous sodium hydroxide (saponification), followed by acidification of the reaction mixture with HCl or other mineral acid, converts an ester to a carboxylic acid and an alcohol. Recall also from Section 13.8 that )3-ketoacids and )3-dicarboxylic acids readily undergo decarboxylation (lose CO2) when heated. The following equations illustrate the results of a Claisen condensation, followed by saponification, acidification, and decarboxylation ... 

Claisen condensation between diethyl phthalate and ethyl acetate, followed by saponification, acidification, and decarboxylation, forms a diketone, C9H6O2. Propose structural formulas for compounds A, B, and the diketone (See Example 15.9)... 

We have described what is commonly known as the acetoacetic ester synthesis and have illustrated the use of ethyl acetoacetate as the starting reagent. This same synthetic strategy is applicable to any j8-ketoester, as, for example, those that are available by the Claisen (Section 19.3A) and Dieckmann (Section 19.3B) condensations. For example, following are structural formulas for two jS-ketoesters available from Dieckmann and Claisen condensations that can be made to tmdergo (1) formation of an enolate anion, (2) alkylation or acylation, (3) hydrolysis followed by (4) acidification, and finally (5) decarboxylation just as we have shown for ethyl acetoacetate. 

The general case of a Claisen condensation followed by saponification, acidification, and decarboxylation gives a symmetrical ketone product. 

CHS (Fig. 2), the most studied member of the type III PKS family, is a ubiquitous enzyme in plants that catalyzes the first committed step in flavonoid biosynthesis, the elongation of the starter molecule 4-coumaroyl-CoA by addition of three acetate units derived from three molecules ofmalonyl-CoA [19]. After binding ofthe 4-coumaroyl moiety to the active site Cysl64, sequential polyketide chain elongation is initiated by the decarboxylation of malonyl-CoA to form an acetyl-CoA carbanion, followed by an intramolecular Claisen condensation step and subsequent cyclization and aromatization, yielding chalcone [20]. 

These prodncts are formed through nucleophiUc attack followed by Claisen condensation (intermediate A), intramolecular cyclization and dehydration (intermediate B), and then by aromatization (after hydrolysis and decarboxylation) through involvement of the phenolic hydroxy group. At the same time, chromone 130a reacts with cyanoacetamide, A-methyl cyanoacetamide, and cyanoacetohydrazide in the presence of sodium ethoxide, affording 2-pyridones 212 in good yields [104] (Scheme 68). 

After subsequent Claisen condensation with a second equivalent acetyl-CoA, 4-(l-methyl-pyrrolidin-2-yl)-3-oxobu-tanoyl-CoA 25a/b is formed, the link between pyrrolidine and tropane alkaloid biosynthesis. From this intermediate, characteristic pyrrolidine alkaloids, such as hygrine (26) and cuscohygrine (27), two alkaloids commonly found in coca leaves [9], are formed either directly by hydrolysis and subsequent decarboxylation (for 26) or via an additional Mannich reaction with the aforementioned IV-methyl-A -pyrrolinium cation (23) followed by hydrolysis and decarboxylation (27). 

To accommodate this new finding and the previous results, we considered a new pathway (Scheme 3), in which acetate or its derivative condenses with arginine followed by decarboxylation. Such Claisen-type condensation on alpha-amino acid has some precedent in biochemical systems (6). To prove this hypothesis, we synthesized [2- C, 2-arginine and ornithine and fed to A, flos-aquae (5). 

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