Acyl transfer, pathway

In this sense, Persson et al. carried out the first DYKAT process of symmetrical diols via coupled Shvo s catalyst 2 and CALB catalysis. Thus, 1 1 mixtures of meso-and R,S-diols were transformed to enantiomerically pure diacetates in moderate yields and high ee values (Figure 14.12a), although undesired meso-diacetates were formed by an intramolecular acyl-transfer pathway [26]. 

Steps 1-2 of Figure 29.5 Acyl Transfers The starting material for fatty-acid synthesis is the thioesteT acetyl CoA, the ultimate product of carbohydrate breakdown, as we ll see in Section 29.6. The synthetic pathway begins with several priming reactions, which transport acetyl CoA and convert it into more reactive species. The first priming reaction is a nucleophilic acyl substitution reaction that converts acetyl CoA into acetyl ACP (acyl carrier protein). The reaction is catalyzed by ACP transacyla.se. 

Acetoxymethyl carbamates of primary amines behaved differently from the pathway depicted in Fig. 8.19, the predominant reaction being intramolecular acyl transfer to generate the A-acetylated amine as the major product [209]. This parasitic reaction was observed in buffer and proportionally less in plasma, disqualifying (acyloxy)methyl carbamates for use as prodrugs of primary amines. However, this type of derivative appears well suited for the preparation of prodrugs of secondary amines, as documented below. 

Figure 7.12 The process of p-oxidation of fatty acyl-CoA in mitochondria. This cycle of reactions converts all the carbon atoms in fatly acyl-CoA to acetyl-CoA which is oxidised in the Krebs cycle. In the first oxidation, hydrogen atoms are transferred to FAD and in the second to NAD. Both reduced coenzymes are oxidised via the electron transfer pathway.

The above types of catalysis function by stabilizing the transition state of the reaction without changing the mechanism. Catalysts may also involve a different reaction, pathway. A typical example is nucleophilic catalysis in an acyl transfer or hydrolytic reaction. The hydrolysis of acetic anhydride is greatly enhanced by pyridine because of the rapid formation of the highly reactive acetylpyridinium ion (equation 2.12). For nucleophilic catalysis to be efficient, the nucleophile... 

In discussing possible mechanisms for the reactions catalyzed by E. coli glutaminase in Section I, it was concluded that either a two-step acylation-deacylation pathway or a one-step route, displacement by the ultimate nucleophile, could be accommodated by the results. It may be noted that any single displacement mechanism for a group transfer reaction requires that both incoming and outgoing substituent groups associate with the enzyme at the same time... 

Better for the lateral lithiation of phenols are the N,N-dialkylcarbamate derivatives 444. These may be lithiated with LDA, allowing complete selectivity for the lateral position, presumably because this is the thermodynamic product.192 With s-BuLi ortholithiation is the predominant reaction pathway. If the lateral organolithium 445 is warmed to room temperature, an acyl transfer from O to C takes place, analogous to the anionic ortho-Fries (see section 2.3.2.1.4), giving amide 446.365... 

Further impetus for consideration of the role of proton transfer came with the discovery of the mechanism for acyl-transfer involving proton transfer to 0-2. This led to consideration of the possibility that glycoside formation under neighboring-group participation conditions might be triggered by an analogous pathway of proton... 

The most prevalent pathway for acyl transfer catalyzed by acids, bases, or enzymes in condensed phase is an addition-elimination sequence involving the formation of tetrahedral intermediates, I (Scheme I) (6). A similar... 

Other acyl group donors include thioesters and esters. As we will see in the final section of this chapter, acyl transfer reactions are very important in nature, particularly in the pathways responsible for breakdown of food molecules and harvesting cellular energy. 

Fig. 9. Biosynthesis of platelet-activating factor (PAF) via the remodeling pathway. Lyso-PAF, the immediate precursor of PAF, can be formed from l-alkyl-2-acyl-sn-glycero-3-phosphocholine through the direct action of (I) PLAj or (II) CoA-independent transacylase. The lysoplasmenylethanolamine (or other potential ethanolamine- and choline-containing lysoglycerophospholipids) is thought to be generated by (III) a PLAj that exhibits a high degree of selectivity for substrates with an atachidonoyl moiety at the sn-2 position. The transacylase (II) appears to possess both acyl transfer and PLAj hydrolytic activities. Lyso-PAF produced by either the transacylation (II) or direct PLAj (I) action can be acetylated to form PAF by (IV) an acetyl-CoA acetyltransferase.

In principle, reaction of an oxazole, e.g., 15 with 2 could yield triamides 693 and/or 696 via two reasonable pathways (Scheme 1.194). In the first case, path A, [4 + 2] cycloaddition of 02 to 15 would yield an oxazole-2,5-endoperoxide 691. Rearrangement of 691 to an imino-anhydride 692 by a Bayer-Villiger-like reaction and subsequent O-acyl to A/-acyl transfer would produce triamide 693. Alternatively, [2 + 2] cycloaddition of 02 to 15 would produce the dioxetane 694, cleavage of which would then yield a second imino-anhydride 695, which could also undergo an O-acyl to /V-acyl transfer reaction to produce triamide 696. 

A simple example of an acyl transfer is the reaction of an acid chloride with an alcohol (Scheme 10.21). No catalysis is necessary due to the high reactivity of an acid chloride. The alcohol performs a direct nucleophilic attack on the electron deficient carbonyl carbon. The reaction is therefore very sensitive to the nucleophile. For example, the Swain-Scott s value for acyl transfer from benzoyl chloride is 1.43, indicating that the reaction is more sensitive to the nucleophile than is the 5 2 reaction on methyl iodide. Elimination of the chloride follows a typical 1,2-elimination pathway. The proton is removed from the intermediate either prior to or subsequent to chloride departure. 

---