Amino aldol cleavage

MECHANISM FIGURE 22-18 Tryptophan synthase reaction. This enzyme catalyzes a multistep reaction with several types of chemical rearrangements. An aldol cleavage produces indole and glyceraldehyde 3-phosphate this reaction does not require PLP. Dehydration of serine forms a PLP-aminoacrylate intermediate. In steps and this condenses with indole, and the product is hydrolyzed to release tryptophan. These PLP-facilitated transformations occur at the /3 carbon (C-3) of the amino acid, as opposed to the a-carbon reactions described in Figure 18-6. The /3 carbon of serine is attached to the indole ring system. Tryptophan Synthase Mechanism... 

Vicinal effects can also play a part in the course of the reaction utilizing Oppenauer conditions. 1,3-Diols or / -amino alcohols may not react, presumably on account of formation of an aluminum complex.5 5 46b> If oxidation were to take place it would probably be followed by dehydration to give an unsaturated ketone. Retro-aldol cleavage has been found to occur with a 17,21-dihydroxy steroid.32 The 11 -hydroxyl group which is generally inert to Oppenauer oxidation will react if a hydroxyl group is present on the... 

Pyridoxal-5 -phosphate promotes decarboxylations, racemizations, transaminations, aldol cleavages, and elimination reactions of amino acid substrates. 

The reactions catalyzed by transaminases are anergonic as they do not require an input of metabolic energy. They are also freely reversible, the direction of the reaction being determined by the relative concentrations of the amino acid-keto acid pairs. Pyridoxal phosphate is not just used as the coenzyme in transamination reactions, but is also the coenzyme for several other reactions involving amino acids including decarboxylations, deaminations, racemizations and aldol cleavages. 

Transamination is just one of a wide range of amino acid transformations that are catalyzed by PLP enzymes. The other reactions catalyzed by PLP enzymes at the a-carbon atom of amino acids are decarboxylations, deam-inations, racemizations, and aldol cleavages (Figure 23.12). In addition, PLP enzymes catalyze elimination and replacement reactions at the P-carbon atom (e.g., tryptophan synthetase Section 24.2.11) and the y-carbon atom (e.g., cytathionine P-synthase, Section 24.2.9) of amino acid substrates. Three common features of PLP catalysis underlie these diverse reactions. 

Transaldolase transfers a 3-carbon keto fragment from sedoheptulose 7-phos-phate to glyceraldehyde 3-phosphate to form erythrose 4-phosphate and fructose 6-phosphate (Fig. 29.9). The aldol cleavage occurs between the two hydroxyl carbons adjacent to the keto group (on carbons 3 and 4 of the sugar). This reaction is similar to the aldolase reaction in glycolysis, and the enzyme uses an active amino group, from the side chain of lysine, to catalyze the reaction. 

Decarboxylases are known for their roles in a wide variety of catabolic and anabolic pathways, including decarboxylation of a- and p-keto acids, amino acid conversions, and carbohydrate biosynthesis. Mechanistically, a decarboxylation has parallels to retro-aldol cleavage reactions (Figure 1.32). 

The versatile reactivity of the minor isomer 13 has been further explored by Fleet s group. When the azide is reduced and the acetal removed, dte resulting amino compound 17 presumed to be less susceptible to reversible aldol reaction) is opened to give the anticipated 18, but a minor product 19 is obtained via reversible aldol cleavage of the C2-C3 bond. The isomeric amino compound 20 undergoes lactone hydrolysis to 16 and 21, with 21 as the major product derived from retroaldol-reclosure (Scheme 4). 

From the observation of Dakin (i) that phenylserine is oxidized in the body to benzoic acid, Knoop (40) had the insist to propose that the catabolism of jS-hydroxy-a-amino adds leads to the formation of glycine. This has been proven correct by more recent investigations and a number of enzymes have been discovered that catalyze an aldol cleavage of these amino acids which is reversible, as shown in Eq. (4) below. 

By retro-aldol cleavages of the 1-deoxyosone short-chain dicarbonyls like diacetyl, methylglyoxal or hydroxydiacetyl are formed which - like the deoxyosones - may participate in the Strecker degradation of amino acids, thus creating volatile flavor components 17,18). On the other hand, the 1-deoxyosone undeigoes several cyclization reactions yielding e.g. acetylfiiran, maltol, isomaltol, furaneol and 5-hydroxy-5,6-dihydromaltol (DHM) (75). 

Photochemical transformations of the hydroxy-substituted amino acids serine 1 and threonine have been described, and mechanistic outHnes based on an electron or a hydrogen transfer key-step have been discussed. The broad spectrum of photoproducts obtained from the C-unprotected serine derivative 1 originated from both reactive sites of the molecule the carboxyl and the hydroxy group (Scheme 1 Table 84.1). Product 4 derived from primary a-photodecarboxylation, and further 5-elimination led to the olefinic compound 2. N-Methylphthalimide 3 was formed via initial extrusion of formaldehyde foUowed by rapid a-photodecarboxylation vide infra). When this a-photodecarboxylation site was blocked, as for the corresponding methyl ester, solely retro-Aldol cleavage occurred. Although azomethine... 

The biologically active form of vitamin Bg is pyridoxal-5-phosphate (PEP), a coenzyme that exists under physiological conditions in two tautomeric forms (Figure 18.25). PLP participates in the catalysis of a wide variety of reactions involving amino acids, including transaminations, a- and /3-decarboxylations, /3- and ") eliminations, racemizations, and aldol reactions (Figure 18.26). Note that these reactions include cleavage of any of the bonds to the amino acid alpha carbon, as well as several bonds in the side chain. The remarkably versatile chemistry of PLP is due to its ability to... 

This chapter deals mainly with the 1,3-dipolar cycloaddition reactions of three 1,3-dipoles azomethine ylides, nitrile oxides, and nitrones. These three have been relatively well investigated, and examples of external reagent-mediated stereocontrolled cycloadditions of other 1,3-dipoles are quite limited. Both nitrile oxides and nitrones are 1,3-dipoles whose cycloaddition reactions with alkene dipolarophiles produce 2-isoxazolines and isoxazolidines, their dihydro derivatives. These two heterocycles have long been used as intermediates in a variety of synthetic applications because their rich functionality. When subjected to reductive cleavage of the N—O bonds of these heterocycles, for example, important building blocks such as p-hydroxy ketones (aldols), a,p-unsaturated ketones, y-amino alcohols, and so on are produced (7-12). Stereocontrolled and/or enantiocontrolled cycloadditions of nitrones are the most widely developed (6,13). Examples of enantioselective Lewis acid catalyzed 1,3-dipolar cycloadditions are summarized by J0rgensen in Chapter 12 of this book, and will not be discussed further here. 

Dipolar cycloaddition reactions between nitrile oxides and aUcenes produce 2-isoxazolines. Through reductive cleavage of the N—O bond of the 2-isoxazohnes, the resulting heterocycles can be readily transformed into a variety of important synthetic intermediates such as p-hydroxy ketones (aldols), p-hydroxy esters, a,p-unsaturated carbonyl compounds, y-amino alcohols, imino ketones and so forth (7-12). 

Aliphatic nitro compounds are versatile building blocks and intermediates in organic synthesis,14 15 cf. the overview given in the Organic Syntheses preparation of nitroacetaldehyde diethyl acetal.16 For example, Henry and Michael additions, respectively, lead to 1,2- and 1,4-difunctionalized derivatives.14 18 1,3-Difunctional compounds, such as amino alcohols or aldols are accessible from primary nitroalkanes by dehydration/1,3-dipolar nitrile oxide cycloaddition with olefins (Mukaiyama reaction),19 followed by ring cleavage of intermediate isoxazolines by reduction or reduction/hydrolysis.20 21... 

Except for some vitamin B12-dependent reactions, the cleavage or formation of carbon-carbon bonds usually depends upon the participation of carbonyl groups. For this reason, carbonyl groups have a central mechanistic role in biosynthesis. The activation of hydrogen atoms (3 to carbonyl groups permits (3 condensations to occur during biosynthesis. Aldol or Claisen condensations require the participation of two carbonyl compounds. Carbonyl compounds are also essential to thiamin diphosphate-dependent condensations and the aldehyde pyridoxal phosphate is needed for most C-C bond cleavage or formation within amino acids. 

N-Methylated y-amino-p-hydroxy acids are accessible by the usual synthetic sequences, i.e. aldol condensation or y-amino-P-oxo ester reduction, starting from the corresponding N-methylated a-amino acids, but are obtained with low diastereoselectivity. 61-63 Alternatively, Brown allylboration of the ALBoc-ALMe amino aldehyde 16 (R1 = Bzl, X=Boc, Y = Me) gives the allyhc N-methylated intermediate 27 in 64% yield and 90% de (Scheme 12). 64 Oxidative cleavage of the alkenol is performed using the two-step ozonolysis and sodium chlorite oxidation sequence. 

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