Retroaldol cleavage

The base-catalyzed cleavage of B-hydroxynitrosamines occurs as is shown in equation 4 to produce a smaller fragment nitrosamine and the carbonyl compound. This reaction is formally analogous to the retroaldol cleavage of a B-hydroxyaldehyde or ketone and as we will see below, appears to be mechanistically related to this transformation. We have demonstrated that this reaction occurs with a wide range of structurally variant B-hydroxynitrosamines 5). Table 1 lists the structure, yield, and reactivity estimate of the compounds that we have studied so far under the same conditions. A variety of conditions have been used to in-... 

Although our investigation of the mechanism of this transformation is incomplete at present, our data are consistent with the view that the fragmentation is an example of the retroaldol cleavage of a B-hydroxynitrosamine as depicted in Scheme 2. Such a hypothesis requires that the a-nitrosamino carbanion possess a stability similar to that of an enolate ion. Keefer and Fodor s discovery of the acidity of the a-hydrogen of the nitrosamino function ( ) and Seebach and Ender s extensive utilization of this fact in organic synthesis (7 ) adequately substantiate this point. 

If the fragmentation of the alkoxide is rate-determining and endothermic, one would expect the transition state structure to resemble the products and thence be influenced by the relative stability of the carbonyl fragment. A transformation similar to the retroaldol cleavage of B-hydroxynitrosamines has been observed. Kruger reported that the treatment of 2-ketopropylpropylnitrosa-mine with refluxing potassium hydroxide in alcohol led to the production of methyl propylnitrosamine as is illustrated in equation 6 (10). This transformation is also under study in our laboratory. 

CH3 to Br to N02. The product / -diketones (largely enolic) were susceptible to hydrolytic retroaldol cleavage, a result which affected the UV spectrum of the reacting solutions. Only when this process occurred at a rate similar to that of the enamine hydrolysis, was the first-order behavior of the time course compromised, and in these cases correction for loss of dione was made. 

Steinmeyer and Neef (92TL4879) have used nitrile oxide cycloaddition, followed by ring-opening of the cycloadduct (138), to give the j8-hydroxy ketone (139), and subsequent retroaldol cleavage to the ketone... 

A mechanistic rationalization is given in Scheme 7 (HMPA additive) and Scheme 8 (2iiCl2 additive) respectively. In both Schemes analogous adducts (218) and (223) are formed stereoselectively, which rearrange to the 7-lactone alkoxides (219) and (224). In the presence of HMPA, retroaldol cleavage to... 

Retroaldol cleavage of 20-methyl-20-hydroxy-l 7a-pregnan-16-ones (526 R = Me, R = P-H) to afford androstan-16-ones occurs more readily than with the 17 -epimer. Similar base treatment of the 20a-hydroxypregnane (526 R = H, R = a-H) resulted only in dehydration to the 17-ene (527) which, only after prolonged refluxing with methanolic base, yielded the androstan-16-one. 

Figure 13 Retroaldol cleavage of serine (a), followed by condensation between formaidehyde and H4PteGiu (b).

Figure 15 Modified, concerted retroaldol cleavage mechanism proposed for the SHMT reaction.

The action of hot aqueous alkali on heteratisine or oxoheteratisine causes only hydrolytic opening of the lactone ring. With the corresponding ketones, however, profound degradation occurs under-these conditions. The products lack lactone or carboxyl groups (no IR absorption for S-lactone insoluble in alkali) and may be formed by decarboxylation of the j8-keto acids CDX and CDXI, respectively, which are formed by retroaldol cleavage of the corresponding j8-hydroxy ketone system (CDVIII, CDIX). 

The intermediate 3 may also be decarboxylated, as shown in Scheme 2, and the decarboxylated imine 8, on protonation followed by hydrolysis, will yield the amine 9 and PLP I. This process is catalyzed by amino acid decarboxylases. Retroaldol cleavage of a suitable ) -hydroxy amino acid would be encouraged by the electron sink in a similar manner. 

A -peptide sequence containing ACHC residues in combination with -homolysine (j0 -hLys) residues was synthesized in order to catalyze the retroaldol cleavage of /i-hydroxyketone 135 through amine catalysis (Figure 50a). The mechanism shown in Figure 50(a)... 

Condensation of formaldehyde with D-[ C]glucose catalysed by 3—5 M calcium hydroxide at 100 °C gave D-fructose, D-mannose, D-arabinose, dihydroxyacetone, glyceraldehyde, and glycolaldehyde. Isotope studies confirmed that the rate of retroaldol cleavage of the aldose was considerably less than the rate of carbohydrate synthesis. The pH changes and the complex formation of the same reaction with either calcium hydroxide or lead hydroxide have been investigated. ... 

The stable secondary products of the Maillard reaction, that are isolated from many different reaction mixtures and have known structures, can be generally assigned to a definite deoxyosone by a series of plausible reaction steps (enolization, elimination of water, retroaldol cleavage, substitution of an amino function for a hydroxy function etc.). 

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