Decarboxylating condensation

Decarboxylative condensations of this type are sometimes carried out in pyridine, which cannot form an imine intermediate, but has been shown to catalyze the decarboxylation of arylidene malonic acids.215 The decarboxylation occurs by concerted decomposition of the adduct of pyridine to the a, 3-unsaturated diacid. 

The regio- and stereochemical outcome of the intermolecular 1,3-dipolar cycloaddition of an azomethine ylide generated by the decarboxylative condensation of an isatin with an a-amino acid was unambiguously determined by a single-crystal X-ray study of the spirocyclic heterocycle 49 (R1 =4-Br, R2 = H, X = CH2) <1998TL2235>. 

When ethyl (3-methyleneoxindole)acetate was used as the dipolarophile in the decarboxylative condensation between isatin 432 and iV-benzylglycine, double spiro compounds 52 and 53 were obtained. These have the same configurations as some related molecules that were reported by Casaschi et al. <1994H(37)1673>. 

The six-membered aromatic A ring originates from three units of malonyl-CoA, produced from citrate precursors through the activity of a cytosolic acetyl-CoA carboxylase (ACC) (Fatland and others 2004) (see Fig. 5.1). These three malonyl-CoA units are added through sequential decarboxylation condensation reactions and actually represent the first committed step toward flavonoid biosynthesis. 

Sphingolipids are biosynthesized by adding head groups to the ceramide moiety. Sphinganine, also termed dihy-drosphingosine, is biosynthesized by a decarboxylating condensation of serine with palmitoyl-CoA to form a keto intermediate, which is then reduced by NADPH (Fig. 3-9). 

In the synthesis of fatty acids the acetyl irnits are condensed and then are reduced to form straight hydrocarbon chains. In the oxo-acid chain elongation mechanism, the acetyl unit is introduced but is later decarboxylated. Tlius, the chain is increased in length by one carbon atom at a time. These two mechanisms account for a great deal of the biosynthesis by chain extension. However, there are other variations. For example, glycine (a carboxylated methylamine), under the influence of pyridoxal phosphate and with accompanying decarboxylation, condenses with succinyl-CoA (Eq. 14-32) to extend the carbon chain and at the same time to introduce an amino group. Likewise, serine (a carboxylated ethanolamine) condenses with... 

Various approaches have been used to prepare pyrroles on insoluble supports (Figure 15.1). These include the condensation of a-halo ketones or nitroalkenes with enamines (Hantzsch pyrrole synthesis) and the decarboxylative condensation of N-acyl a-amino acids with alkynes (Table 15.3). The enamines required for the Hanztsch pyrrole synthesis are obtained by treating support-bound acetoacetamides with primary aliphatic amines. Unfortunately, 3-keto amides other than acetoacetamides are not readily accessible this imposes some limitations on the range of substituents that may be incorporated into the products. Pyrroles have also been prepared by the treatment of polystyrene-bound vinylsulfones with isonitriles such as Tosmic [28] and by the reaction of resin-bound sulfonic esters of a-hydroxy ketones with enamines [29]. 

The polyketide synthases responsible for chain extension of cinnamoyl-CoA starter units leading to flavonoids and stilbenes, and of anthraniloyl-CoA leading to quinoline and acridine alkaloids (see page 377) do not fall into either of the above categories and have now been termed Type TTT PKSs. These enzymes differ from the other examples in that they are homodimeric proteins, they utilize coenzyme A esters rather than acyl carrier proteins, and they employ a single active site to perform a series of decarboxylation, condensation, cyclization, and aromatization reactions. 

Many desirable meat flavor volatiles are synthesized by heating water-soluble precursors such as amino acids and carbohydrates. These latter constituents interact to form intermediates which are converted to meat flavor compounds by oxidation, decarboxylation, condensation and cyclization. 0-, N-, and S-heterocyclics including furans, furanones, pyrazines, thiophenes, thiazoles, thiazolines and cyclic polysulfides contribute significantly to the overall desirable aroma impression of meat. The Maillard reaction, including formation of Strecker aldehydes, hydrogen sulfide and ammonia, is important in the mechanism of formation of these compounds. 

The chalcone synthase (CHS) (EC 2.3.1.74) superfamily of type III Polyketide synthases (PKSs) are pivotal enzymes in the biosynthesis of plant polyphenols. They are structurally and mechanistically different from the modular type I and the dissociated type II PKSs of bacterial origin the simple homodimer of 4CM-5 kDa proteins performs a complete series of decarboxylation, condensation, cyclization,... 

Aromatic polyketides are structurally diverse, often polycyclic molecules that are derived from unreduced polyketone chains. This group of compounds is produced with the help of type II polyketide synthase (PKS), a complex of enzymes that catalyzes the iterative decarboxylative condensation of malonyl-CoA extender units with an acyl starter unit [70], The carbon framework of aromatic polyketides is further decorated with different functionalities, and carbohydrates are often one of them. Their presence has profound effects on physico-chemical and biological properties of aromatic polyketides. For example, anthracycline aglycones are stable and unpolar, while polyglycosylated anthracyclines are quite polar and often... 

Most of the bimolecular absolute asymmetric syntheses are limited to 2+2 cyclobutane formation or polymerization of olefins. Koshima et al. reported a unique example of bimolecular reaction whereby acridine 20 and diphenylacetic acid are assembled in a 1 1 molar ratio by hydrogen bonding, and crystallized in a chiral space group, P2i2i2i.[18] Irradiation of the crystals caused stereospecific decarboxylating condensation to give chiral 21 in 33-39% ee. 

The preparation of ketones by dehydrogenation of secondary alcohols over zinc and copper catalysts and the decarboxylation condensation of acids over manganous oxide or thoria have been adequately covered by standard reference books on catalysis. However, the more complete but equally serviceable catalytic syntheses involving either an aldol or a Tischenko ester type of condensation have been virtually ignored. 

The oxidation of coke molecules begins by their hydrogen atoms with formation of oxygenated compounds which can undergo various reactions decarbonylation, decarboxylation, condensation. The greater the density of the acid sites the faster the oxidation of coke. Radical cations formed through reaction of molecular oxygen with coke molecules adsorbed on protonic sites would be intermediates in coke oxidation on acid zeolites. 

Fig. 4. X-ray determined protein crystal structures of multienzyme ensembly lines, (a) Mammalian fatty acid synthase at 4.5 A resolution (PDB 2cf2). Domain organization A starter substrate, acetyl-CoA or malonyl-CoA, gets loaded onto the acyl-carrler protein (ACP/absent in the structure) via the malonyl-CoA-/acetyl-CoA-ACP transacylase (MAT). Then, the ketoacyl synthase (KS) catalyzes a decarboxylative condensation reaction and forms the B-ketoacyl-ACP. This is followed from a reduction reaction catalyzed by the B-ketoacyl reductase (KR). Subsequently, the Intermediate gets dehydrated by a dehydratase (DH) and additionally reduced by a B-enoyl reductase (ER). The product gets released from the ACP by a thloesterase (absent in the structure), (b) Module 3 of 6-deoxyerthronolide B synthase at 2.6 A resolution (PDB 2qo3) bound to the inhibitor cerulin. The ketosynthase (KS) - acyltransferase (AT) di-domain is part of the large homodimeric polypeptide involved in biosynthesis of erythromycin from Saccharopolyspora erythraea...

Figure 2 (A) Decarboxylative condensation during polyketide synthesis. (B) Reductive steps in type 1PKS...

Type III PKSs are found widely among plants and bacteria. They consist of a homodimer ketosynthase that iteratively condenses malonyl-CoA to give relatively smaller aromatic polyketides than those discussed in the last section (Figure 10). Type III PKS differs from Type II PKS in two important aspects (1) the KS directly recraits mal-onyl-CoA in the absence of an acyltransferase or an AGP and (2) the KS active site catalyzes decarboxylative condensation and chain elongation, and also defines the regioselectivity of intramolecular cyclization. The relatively simple mode of chain assembly has made Type III PKSs attractive targets for engineered biosynthesis. 

Following loading of acetyl and malonyl groups onto the P subunit of the enzyme, additional intramolecular transfers must occur to prepare the substrates for the decarboxylative condensation reaction which is catalyzed by the -ketoacyl synthase domain of the a subunit. The end result of these transfers is the thio-esterification of malonate by the phosphopantetheine thiol and of acetate by Cys-1305(a) of the -keto synthase active site. This cysteine has been shown to have a dramatically lowered pK (<5), which would encourage its reactivity [65]. 

Decarboxylative condensation of the malonyl-ACP onto the -ketosynthase-bound growing acyl chain is likely to be analogous to the corresponding reaction catalyzed by the E. coli -ketoacyl synthase. Once formed, the acetoacetyl derivative remains attached to the phosphopantetheine cofactor during subsequent steps of ketoreduction, dehydration, and enoyl reduction, before the growing fatty acid is transferred to the Cys-1305 thiol in preparation for another round of elongation. 

The basic assembly cycle for both polyketide and fatty acid biosynthesis is shown in Fig. 1 in which a starter unit, normally acetate is transferred to the ketosynthase (KS) or condensing enzyme which catalyzes a decarboxylative condensation with... 

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