Retro-aldol cleavage

This cleavage is a retro aldol reaction It is the reverse of the process by which d fruc tose 1 6 diphosphate would be formed by aldol addition of the enolate of dihydroxy acetone phosphate to d glyceraldehyde 3 phosphate The enzyme aldolase catalyzes both the aldol addition of the two components and m glycolysis the retro aldol cleavage of D fructose 1 6 diphosphate... 

The reactions that accomplished the conversion of intermediate 16 into intermediate 23 have taken place very smoothly. It is worth acknowledging that the //-hydroxy lactam moiety did not, at any stage, participate in any undesirable side reaction processes. The stability of the //-hydroxy lactam substructure in the presence of basic reagents is particularly noteworthy since a destructive retro-aldol cleavage reaction could have conceivably occurred on several occasions. The stability of this potentially labile moiety permits all of the desired transformations leading from 16 to 23 to be conducted without prior protection of the C-8 hydroxyl group. 

The most convenient method is the formation of two equivalents of (25) by retro-aldol cleavage from commercially available (26) by the combined action of FruA and triose phosphate isomerase (Figure 10.18 inset) [84]. This scheme has been extended into a highly integrated, artificial metabolism for the efficacious in situ preparation of (25) from inexpensive feedstock such as glucose and fructose (two equivalents of... 

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... 

While the lyases that transfer a pyruvate unit form only a single stereogenic center, the group of dihydroxyacetone-phosphate-(DHAP, 41)-dependent aldolases create two new asymmetric centers, one each at the termini of the new C-C bond. A particular advantage for synthetic endeavors is the fact that Nature has evolved a full set of four stereochemically-complementary aldolases [189] (Scheme 6) for the retro-aldol cleavage of diastereoisomeric ketose 1-phosphates— D-fructose 1,6-bisphosphate (42 FruA), D-tagatose 1,6-bisphosphate (43 TagA), L-fuculose 1-phosphate (44 FucA), and L-rhamnulose 1-phosphate (45) aldolase (RhuA). In the direction of synthesis this formally allows the... 

Methylation of alcohols1 (6,406). The sensitive aldol product 1 was converted to the corresponding methyl ether in 83% yield by reaction with methyl triflate (15 equiv.) and 2,6-di-r-butylpyridine (30 equiv.) in CHC13 at 80° without retro-aldol cleavage or epimerization. 

It was evident that the aldol reaction had reached equilibrium after 16 hours incubation because the product distribution changed very little after this time. Evidence that the enzyme does indeed catalyze both aldol formation and cleavage on the timescale used was demonstrated by reequilibrating a mixture of sialic acid and D-mannose in the presence of the NANA aldolase. After incubation overnight the mixture contained, in addition to the initial components, KDN and sodium pyruvate, which could only arise through a retro-aldol cleavage of sialic acid followed by aldol formation of KDN. 

The surprising rearrangement of an aminocycloheptenone to the aminoacylcyclo-pentenone skeleton321 is achieved by a nucleophilic attack of the hydroxide ion at the -position of an enaminone, a special reaction known only for a-ketoenamines. This step is followed by a retro-aldol cleavage of the cycloheptanone ring and a subsequent aldol cyclization yields the cyclopentane derivative (equation 240). 

---