Decarboxylative fragmentation

The key intermediate is the hydrofuroxan (122) which facilitates decarboxylative fragmentation in the same manner as in a /3-bromo acid anion. 

Conjugate addition of radicals generated by decarboxylative fragmentation of (diacyloxyiodo)benzene 564 to dehydroamino acid derivatives 563 has been used in the synthesis of diaminopimelic acid analogues 565 (Scheme 3.223) [612]. 

This is the branch-poiat differentiatiag phenylalanine (25, R = H) from tyrosiae (25, R = OH). Both phenylalanine and tyrosiae contain an aryl ring, a three-carbon side chain (a Cg—Cg fragment), and a nitrogen. Decarboxylation yields a two-carbon side chain (a Cg—Cg fragment), eg, 2-phenethylamine (59, R = H) from phenylalanine and tyramine (59, R = OH) from tyrosiae, although it is not certain that ia all cases decarboxylation must precede use ia alkaloid constmction. 

Earlier sections have already provided several examples of radical fragmentation reactions, although this terminology was not explicitly used. The facile decarboxylation of acyloxy radicals is an example. 

Acyl radicals can fragment with toss of carbon monoxide. Decarbonylation is slower than decarboxylation, but the rate also depends on the stability of the radical that is formed. For example, when reaction of isobutyraldehyde with carbon tetrachloride is initiated by t-butyl peroxide, both isopropyl chloride and isobutyroyl chloride are formed. Decarbonylation is competitive with the chlorine-atom abstraction. 

A number of lyases are known which, unlike the aldolases, require thiamine pyrophosphate as a cofactor in the transfer of acyl anion equivalents, but mechanistically act via enolate-type additions. The commercially available transketolase (EC 2.2.1.1) stems from the pentose phosphate pathway where it catalyzes the transfer of a hydroxyacetyl fragment from a ketose phosphate to an aldehyde phosphate. For synthetic purposes, the donor component can be replaced by hydroxypyruvate, which forms the reactive intermediate by an irreversible, spontaneous decarboxylation. 

First, these copolymers undergo decarboxylation more readily than any of the homopolymers. Second, decarboxylation involves the units of acrylic add at temperatures which do not affect homopolymers of acrylic acid. In our view, the first phenomenon is accounted for by the effect of separation of conjugation blocks exemplified by this particular chemical reaction. As to the second observation, we believe that decarboxylation under relatively mild conditions (160—170 °C) affects, apparently, the fragments of acrylic acid located at the junctions of the blocks. 

Aliphatic acyloxy radicals undergo facile fragmentation with loss of carbon dioxide (Scheme 3,69) and, with few exceptions,428 do not have sufficient lifetime to enable direct reaction with monomers or other substrates. The rate constants for decarboxylation of aliphatic acyloxy radicals are in the range l 10xl09 M 1 s at 20 °C.429 lister end groups in polymers produced with aliphatic diacyl peroxides as initiators most likely arise by transfer to initiator (see 3.3.2.1,4). The chemistry of the carbon-centered radicals formed by (3-scission of acyloxy radicals is discussed above (see 3.4.1). 

At elevated temperatures, methylene carbons cleave from aromatic rings to form radicals (Fig. 7.44). Further fragmentation decomposes xylenol to cresols and methane (Fig. 7.44a). Alternatively, auto-oxidation occurs (Fig. 1.44b ). Aldehydes and ketones are intermediates before decarboxylation or decarbonylation takes place to generate cresols and carbon dioxide. These oxidative reactions are possible even in inert atmospheres due to the presence of hydroxyl radicals and water.5... 

The cationic pathway allows the conversion of carboxylic acids into ethers, acetals or amides. From a-aminoacids versatile chiral building blocks are accessible. The eliminative decarboxylation of vicinal diacids or P-silyl carboxylic acids, combined with cycloaddition reactions, allows the efficient construction of cyclobutenes or cyclohexadienes. The induction of cationic rearrangements or fragmentations is a potent way to specifically substituted cyclopentanoids and ring extensions by one-or four carbons. In view of these favorable qualities of Kolbe electrolysis, numerous useful applications of this old reaction can be expected in the future. 

Malonic acid or cyanoacetic acid can also be used as the nucleophile. With malonic acid or cyanoacetic acid as reactants, the products usually undergo decarboxylation. This may occur as a concerted fragmentation of the adduct.214... 

Among the most useful radical fragmentation reactions from a synthetic point of view are decarboxylations and fragmentations of alkoxyl radicals. The use of (V-hydroxy-2-thiopyridine esters for decarboxylation is quite general. Several procedures and reagents are available for preparation of the esters,353 and the reaction conditions are compatible with many functional groups.354 f-Butyl mercaptan and thiophenol can serve as hydrogen atom donors. 

Following the enzymatic cleavage, azaquinone methide was rapidly eliminated and decarboxylation occurred, leading to internal cyclization that released a urea derivative and phenol 35. The latter was disassembled as previously described to generate two equivalents of phenol 36, which was further fragmented to release the four reporter groups. 

Barondeau DP, Kassmann CJ, Tainer JA, Getzoff ED (2006) Understanding GFP posttrans-lational chemistry structures of designed variants that achieve backbone fragmentation, hydrolysis, and decarboxylation. J Am Chem Soc 128 4685-4693... 

As predicted, l,2,3,4-13C-labeled acetone dicarboxylate (15) provided an intact three-carbon chain into lycopodine. It also helped to explain why two molecules of pelletierine (12) were not incorporated (Scheme 6.3) [12]. As before, lysine (6) is converted to piperideine (8) via a decarboxylation. Then a Mannich reaction of labeled 15 with 8 provides pelletierine 12. The other half of the molecule to be incorporated must be pelletierine-like (12-CC>2Na), still containing one of the carboxylates. An aldol reaction of the two pelletierine fragments and a series of transformations leads to phlegmarine 9. Oxidation of 9 involving imine formation between N-C5, isomerization to the enamine and then cyclization onto an imine (at N-C13), provides lycopodine 10. Phlegmarine 9 and lycopodine 10 are proposed as... 

The only problem for the matrix-isolation of 21 consisted in the non-availability of a reasonable diazo precursor molecule suited for this technique. But since we already had experience with the preparation of 2,3-dihydrothiazol-2-ylidene46 (see below) by photofragmentation of thiazole-2-carboxylic acid we tried the same method with imidazole-2-carboxylic acid (20). Indeed, irradiation of 20 with a wavelength of 254 nm leads to decarboxylation and the formation of a complex between carbene 21 and CO2. This is shown by the observation that the experimental IR spectrum fits only with the calculated spectrum of complex 21-CC>2 (calculated stabilization energy relative to its fragments 4.3 kcal mol-1). The type of fixation of CO2 to 21 is indicated in the formula S-21 C02. 

The detailed mechanism of inhibition of TEM-2 (class A) enzyme with clavulanate has been established (Scheme 1) [23,24], The inhibition is a consequence of the instability of the acyl enzyme formed between the /1-lactam of clavulanate and the active site Ser-70 of the enzyme. In competition with deacylation, the clavulanate acyl-enzyme complex A undergoes an intramolecular fragmentation. This fragmentation initially provides the new acyl enzyme species B, which is at once capable of further reaction, including tautomeriza-tion to an entity C that is much less chemically reactive to deacylation. This species C then undergoes decarboxylation to give another key intermediate enamine D, which is in equilibrium with imine E. The imine E either forms stable cross-linked vinyl ether F, by interacting with Ser-130 or is converted to the hydrated aldehyde G to complete the inactivation. 

For identification of AEC, two different strategies for substance-specific identification are amenable in API-FIA-MS-MS [22]. The application of CID in the positive mode led to a destructive ionisation that resulted in the loss of C02, as also observed with other anionic AE derivatives. Under these conditions, the precursor parent ions from a commercial blend subjected to API-CID(+) resulted in a characteristic pattern of product ions containing alkyl as well as ethoxy fragments (m/z 57, 71 and 113 or 89, 133 and 177) slightly different from MS-MS(+) spectra observed with conventional AE compounds. Nevertheless, the presence of AE compounds was imagined because of decarboxylation of AEC. Therefore, the analysis of the mixture of AECs was performed in the ESI-LC-MS-MS mode because of interferences of AE in FIA mode. The ESI-LC-MS-MS(+) spectrum of the decarboxylated parent ion at m/z 558 ([C8H17-0-(CH2-CH2-0)9-CH2-H NH4]+) as also observed... 

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