Carboxylic acid debenzylation

Poly(malic acid) is a biodegradable and bioadsorbable water-soluble polyester having a carboxylic acid in the side chain. The chemoenzymatic synthesis of poly(malic acid) was achieved by the lipase-catalyzed polymerization of benzyl (3-malolactonate, followed by the debenzylation. The molecular weight of poly(benzyl (3-malolactonate) increased on copolymerizafion with a small amount of (3-PL using lipase CR catalyst. ... 

Benzyl esters of carboxylic acids are frequently used in organic synthesis for the protection of carboxyl groups. The C-O bond in benzyl esters can be cleaved more easily than the corresponding benzyl ether bond. The hydrogenolysis of an ester leads to carboxylic acid and toluene. Examples of debenzylation of benzyl esters of carboxylic acids on Pd/C catalysts are summarized in Table 4.4. 

Miki et al. reported the total synthesis of ellipticine (228) starting from N-benzylindole-2,3-dicarboxylic anhydride (852) (714,715). Reaction of (3-bromo-4-pyridyDtriisopropoxyltitanium (1232) with 852 gave 2-acylindole-3-carboxylic acid 1233 in 86% yield. Decarboxylation and debenzylation of 1233 led to the ketone 1234. Wittig olefination of the ketone 1234, followed by catalytic hydrogenation. 

The treatment of 4-oxo-4Z/-pyrido[ 1,2-a]pyrimidine-3-carboxylic acid 429 with phosphorus pentachloride in dichloromethane at 0°C gave acid chloride 430, which reacted with amine 431 in tetrahydrofuran in the presence of /V-methyl-TV-trimethylsilyl trifluoroacetamide at room temperature overnight to give /-substituted 3-carboxamide 432 (88USP4777252). After catalytic debenzylation, the 3-substituent of 4//-pyrido[l, 2-a]py-rimidin-4-one 433 was involved in different reactions to give antibacterial derivative 434 (see Scheme 25). 

The absolute stereochemistry of the trinem 15 has been established and its debenzylated derivative shown to have interesting biological activity in contrast to its 5/3-methoxy epimer <1995BML2535>. The absolute stereochemistry of the amidinium salt 16 was established by X-ray crystallography. This technique of salt formation has been used by several workers to obtain suitable crystalline derivatives from carboxylic acids <1999T3427>. 

In order to introduce the carboxylic function, azide 30 was regioselectively debenzylated at the primary hydroxyl group by controlled treatment with acetic anhydride and trifluoroacetic acid, (14) followed by saponification of the acetate at C-5. The product 31 was finally converted into the carboxylic acid 32 by Jones oxidation. 

Fig. 13.66. Acylation of two different malonic diester enolates with carboxylic acid chlorides. Transformation of the acylation products into ketones by heating after debenzylation (see variant 1) or just heating (variant 2).

Piperidine 141 was synthesized from the Barton-McCombie reaction <75JCSP11574> of 142 which gave the expected amido-ester (96 %) as a 3 2-mixture of diastereomers. The mixture was hydrolyzed to the corresponding carboxylic acid which, upon thermal decarboxylation, gave the desired /V-bcnzyl lactam (85% overall yield) as a single diastereomer whose structure was unequivocally established by a single-crystal X-ray analysis. Reduction of the lactam with LiAlH4 (81%) followed by debenzylation via... 

During a synthesis of the protein kinase C inhibitor Balanol. Lampe and co-workers77 found that deprotection of the tert-butyl ester 30.1 [Scheme 6.30] with trifluoroacetic or formic acid was accompanied by substantial quantities of a debenzylated by-product. The same side reaction accompanied thermolytic cleavage of the terf butyl ester in neutral solvents presumably due to add catalysis by the carboxylic acid product 30.2. Thermolysis in quinoline at 205 °C led cleanly to the desired benzophenone carboxylic acid 30.2 in 68% yield. 

An enantioselective synthesis of TIQ-1-carboxylic acids 91a,b has recently been reported (279). Hydrolysis of the optically active methyl ether enantiomer of hydantoin 103 was accomplished by 20% sodium hydroxide in refluxing methyl cellosolve and led to the dimethyl ether analog of 91a, which was used to establish the absolute configuration of the products. Amino acids 91a,b have also been prepared by chemical resolution of the N,0-benzylated acid 108 with optically active 1-phenylethylamines. Catalytic debenzylation of enantiomer 109a gave... 

The total synthesis of the lichen diphenyl ether epiphorellic acid 1 was achieved in the laboratory of J.A. Elix using the Smiles rearrangement as the key step. The diaryl phenolic ester substrate was heated in dry DMSO in the presence of potassium carbonate, which brought about the rearrangement. The resulting carboxylic acid was converted to the methyl ester with diazomethane and was debenzylated under catalytic hydrogenation conditions. 

The major isomer (1 R,2S,3 R)-79 (39% yield, i.e. 78% of the theoretical maximum) was crystallized, subjected to hydrogenolysis (Pd-mediated N-debenzylation), then hydrolysis to afford (lR,2S,3R)-3-methyl-2-aminocyclopentane carboxylic acid (ds-pentacin) 80 in >98% ee. Epimerization of 79 under basic (t-BuOK/t-BuOH) conditions and subsequent deprotection gave the (1S,2S,3R)-3-methyl-2-aminocyclopentane carboxylic acid (traus-pentacin). 

Preferential debenzylation of carboxylic acid esters s. 16,621 COOCHgCeHs COOH... 

Fluorinated indoles reveal very similar properties in comparison to their non-fluorinated analogues. However, it should be noted that the chemistry of monofluori-nated indoles (with fluorine atom attached to both 2 and 3 position) is scarcely studied. For example, 3-fluoroindole derivative 19a was debenzylated to give indole carboxylic acid ester 157 quantitatively the latter one was converted into amide 159 by hydrolysis followed by reaction with the corresponding amine in the presence of BOP reagent [9a]. Nitrogen atom in case of 3-fluorosubstituted indole derivatives has usual nucleophilicity and can participate in standard indole reactions, for example reaction with tosyl chloride provided V-sulfonylation product in 61 % yield [15]. 

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