Retro-aldol reactions

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... 

Cleavage reactions of carbohydrates also occur on treatment with aqueous base for prolonged periods as a consequence of base catalyzed retro aldol reactions As pointed out m Section 18 9 aldol addition is a reversible process and (3 hydroxy carbonyl com pounds can be cleaved to an enolate and either an aldehyde or a ketone... 

A number of other valuable aroma chemicals can be isolated from essential oils, eg, eugenol from clove leaf oil, which can also, on treatment with strong caustic, be isomerked to isoeugenol, which on further chemical treatment can be converted to vanillin (qv). Sometimes the naturally occurring component does not requke prior isolation or concentration, as in the case of cinnamaldehyde in cassia oil which, on dkect treatment of the oil by a retro-aldol reaction, yields natural ben2aldehyde (qv). This product is purified by physical means. 

In E. coli GTP cyclohydrolase catalyzes the conversion of GTP (33) into 7,8-dihydroneoptetin triphosphate (34) via a three-step sequence. Hydrolysis of the triphosphate group of (34) is achieved by a nonspecific pyrophosphatase to afford dihydroneopterin (35) (65). The free alcohol (36) is obtained by the removal of residual phosphate by an unknown phosphomonoesterase. The dihydroneoptetin undergoes a retro-aldol reaction with the elimination of a hydroxy acetaldehyde moiety. Addition of a pyrophosphate group affords hydroxymethyl-7,8-dihydroptetin pyrophosphate (37). Dihydropteroate synthase catalyzes the condensation of hydroxymethyl-7,8-dihydropteroate pyrophosphate with PABA to furnish 7,8-dihydropteroate (38). Finally, L-glutamic acid is condensed with 7,8-dihydropteroate in the presence of dihydrofolate synthetase. 

Fructose 1,6-bisphosphate undergoes ring opening and is cleaved by a retro-aldol reaction into glyceraldehyde 3-phosphate and dihydroxyacetone phosphate (DHAP). 

In his first independent work, Helferich prepared y-hydroxyvaleral-dehyde (4-hydroxypentanal) by reduction and ozonolysis of methylhep-tenone, readily available from citral by a retro-aldol reaction. He was able to show that, similarly to the saccharides, this hydroxyaldehyde exists in... 

Quinone methides formed during, for example, alkaline pulping reactions may have other mechanisms for rearomatization. Most commonly, in 8-0-4-, 8-5-, and 8-8-quinone methides QM1-QM3 (Fig. 12.2), retro-aldol elimination of formaldehyde to give styryl aryl ethers or stilbenes is common.40 Retro-aldol reactions using a strong base, for example, diazabicycloundecene (DBU) in CH2CI2 can also provide these compounds conveniently at room temperatures.41 3... 

The Henry (nitroaldol) reaction was reported under very mild reaction conditions, in aqueous media using a stoichiometric amount of a nitroalkane and an aldehyde, in NaOH 0.025 M and in the presence of cetyltrimethylammonium chloride (CTAC1) as cationic surfactant (Eq. 8.94) 240 Good to excellent yields of (i-nitroalkanol are obtained. Under these conditions several functionalities are preserved, and side-reactions such as retro-aldol reaction or dehydration of 2-nitroalcohols are avoided. 

Enzyme Catalyzed. The enzyme aldolases are the most important catalysts for catalyzing carbon-carbon bond formations in nature.248 A multienzyme system has also been developed for forming C-C bonds.249 Recently, an antibody was developed by Schultz and co-workers that can catalyze the retro-aldol reaction and Henry-type reactions.250 These results demonstrate that antibodies can stabilize the aldol transition state but point to the need for improved strategies for enolate formation under aqueous conditions. 

Ring D inversion seems to be a crucial step in biogenetic transformations of protoberberines to related alkaloids such as rhoeadine, retroprotoberberine, spirobenzylisoquinoline, and indenobenzazepine alkaloids. 8,14-Cyclober-bin-13-ol 478 derived from berberine (15) was successively treated with ethyl chloroformate, silver nitrate, and pyridinium dichromate (PDC) in dimethyl-formamide to give the keto oxazolidinone 479 (Scheme 98). Heating of 479 with 10% aqueous sodium hydroxide in ethanol effected hydrolysis, retro-aldol reaction, cyclization, and dehydration to provide successfully the... 

A remarkable combination of a photochemical [2+2] cycloaddition with a retro-aldol reaction and cyclization is the so-called de Mayo reaction. Biichi and coworkers have used this method for the total synthesis of loganin (5-35). Thus, reac-... 

The reduction of P-nitro alcohols with LiAlH4 results in low yields of P-amino alcohols due to the occurrence of a retro-aldol reaction. This problem is resolved by protecting of OH of P-nitro alcohols, as shown in Eq. 6.53."... 

Treatment of all four diasteromers of 72 with sodium or potassium bases yielded stilbenes with high stereoselectivity (Scheme 15) <2003T255>. Two of the diastereomers gave rise to some retro-aldol products. In two cases, hexacoordinate species were identified by the upheld 31P chemical shift (5—112 ppm). It was noted that phosphoranes that ring-closed to form hexacoordinate tricyclic species were the ones that did not undergo the retro-aldol reaction to produce aldehydes. The ring closure was disfavored for intermediates with steric repulsion between trifluoromethyl and phenyl groups. 

Unfortunately, upon treating hydroxy ketone 56 with MeLi for extended reaction times, some sort of fragmentation reaction appeared to occur (Scheme 8.15). While the desired addition product 63 was not seen, the fragmentation that took place may be attributed to a retro-aldol reaction through intermediates such as 60 and 61. The tentatively assigned structure of final product 62 is shown, although it was not fully... 

A total synthesis of functionalized 8,14-seco steroids with five- and six-membered D rings has been developed (467). The synthesis is based on the transformation of (S)-carvone into a steroidal AB ring moiety with a side chain at C(9), which allows the creation of a nitrile oxide at this position. The nitrile oxides are coupled with cyclic enones or enol derivatives of 1,3-diketones, and reductive cleavage of the obtained cycloadducts give the desired products. The formation of a twelve-membered ring compound has been reported in the cycloaddition of one of the nitrile oxides with cyclopentenone and as the result of an intramolecular ene reaction, followed by retro-aldol reaction. 

Ring Opening by Acid, Base, Electrophiles or Nucleophiles 2.1 Retro-aldol Reaction... 

Irradiation of a 12 % solution of acetylacetone in cyclohexene afforded the diketone (2), which should go through the intermediate (7) following a retro-aldol reaction 5 6). This reaction is best known as the de Mayo reaction 7>, which enables the... 

It is noteworthy to point out that the rate of retro-aldol reaction is enhanced by ring strain. Thus, suitably substituted 3-oxygenated carbonyl cyclobutanes would... 

The reduction of (32) with NaBH4 also induced the retro-aldol reaction which would give the syn-compound (33) and finally an epimerization reaction j ould convert (33) to the anti-compound (34)... 

The key step in Biichi s total synthesis of loganin (5i)23 made use of the expansion of a four-membered ring to an oxygen-containing heterocycle by retro-aldol reaction. This strategy was later exploited by Tietze in his total synthesis of hydroxyloganin (54) as well as hydroxyloganic acid (55) 24). 

A solution of the ester (56) and the tetrahydropyranyl ether (57) was irradiated to form the intermediate compound (58), which would rearrange through a retro-aldol reaction and a hemiacetal formation route to the less strained six-membered heterocycle (59). The hemiacetal (59) could be converted to loganin (55) in several steps Z3>. 

Treatment of the ketone (105) with methanolic KOH led to hydrolysis of the acetate group, retro-aldol reaction and aldol cyclization, which eventually afforded a mixture of epimeric alcohols (106) 33). This strategy was used to construct the basic skeletons of various alkaloids, e.g. talatisamine 34), atisine 35) and chasmanine36). 

The combination of the carbonyl group and a / -hydroxyl group allows also the sugar to (a) dissociate in two smaller aldehydes, via the retro-Aldol reaction, or (b) eliminate the OH, via a retro-Michael reaction. 

The peculiar reactivity of epoxides of 5-vinylbarbiturates (10.65, Fig. 10.17) has been discussed in Sect. 10.5.3. Here, we note that hexobarbital epoxide (10.9) shows the same reactivity and decomposes via the same retro-aldol reaction to form 5-(l-methylbutyl)barbiturate [193]. 

Figure 20 Aldolization and retro-aldolization reactions catalyzed by antibodies raised against hapten 31.

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