Retroaldolization

There are at least two routes currently being used to produce natural benzaldehyde. Principal flavor houses are reported to market a product which is derived from cassia oil. The chief constituent of cassia oil is cinnamic aldehyde which is hydrolyzed into its benzaldehyde and acetaldehyde constituents. This is a fermentative retroaldol reaction. Whether this hydrolysis allows the final benzaldehyde product to be considered natural is of great concern. The FDA has reportedly issued an opinion letter that benzaldehyde produced from cassia oil is not natural (15). 

A second example of this strategy is the retrosynthetic simplification of 184 via the equivalent 185 by subsequent application of the tactical combination of retroaldol and [2 + 2] photocycloaddition transforms.50 Various targets which are structurally related to 184 have also... 

Scheme 8.51 Construction of the tricyclic core of phomactin A through a retroaldol reaction.

A 11011-addition procedure based on a tandem retroaldol/epoxide-opening/cycli-zation sequence has been utilized for the elaboration of the dihydrofuran ring of the reduced furanochroman subunit of phomactin A. The strategy utilizes the O-TBS-protected 3-epoxy-(3 -hydroxy ketone 201. Cleavage with TBAF starts the retro-... 

A retroaldol fragmentation subsequent to the addition of p-TsOI I and a small amount of water to epoxide 206, obtained by oxidation of enol ether 205 with DMDO, resulted in the direct formation of dialdehyde hydrate 208, possessing the spirostructure necessary for the construction of the fused-rings core of ( )-ginkoli-de B. Apparently, hydrolysis of the epoxide produces the hemiacetal 207, which undergoes retroaldol fragmentation of the cydobutane to afford the dialdehyde, which forms the stable hydrate 208 (Scheme 8.52) [94]. 

Conventional kinetic resolution of diastereomer mixtures by retroaldolization for preparation of enantiopure arylserines and for a synthetic intermediate of an antiparkinsonism drug (b). 

These results support our hypothesis that there is a retroaldol like cleavage of 3-hydroxynitrosamines which occurs in biological systems. Our results agree with the data of Kruger, Preussmann, and Blattmann. The fact that the tertiary nitros-aminoalcohols undergo the cleavage as well as their secondary counterparts demonstrates that oxidation to a ketone is not a... 

C. Schwarzinger, On the mechanism of thermally assisted hydrolysis and methylation of carbohydrates the contribution of aldol and retroaldol reactions, J. Anal. Appl. Pyrol., 68 69, 137 149 (2003). 

An equilibrium mixture of the cyclohexane- 1,3-dione (42) and its enol form (43) was irradiated in the presence of cyclopentene in MeOH to afford the intermediate (44), which was readily transformed to the tricyclic intermediate (45) and subsequently followed an retroaldolization sequence to give the cyclooctanedione (46) in 90 % yield. When refluxed with titanium trichloride and K metal in THF for 5 min., compound (46) gave the diol (47) 21K... 

Photo-addition of allene to the enone (90) yield adduct (91) in 75 % yield, which was subjected to ketalization in 77% yield. Epoxidation of (92) with perbenzoic acid followed by chromatography on alumina afforded two expoxides (93) and (94). Both (93) and (94) could be converted separately through (95) and (96) respectively which was the common intermediate leading to isoishwarane (98) and ishwarane following a deketalization-retroaldol-aldol process to furnish the keto-alcohol (97) (99) 30>. 

The deketalization-retroaldol-aldol procedure was applied to compound (100). Acid catalyzed deketalization, followed by the retroaldol-aldol process afforded (101), which could be transformed to the diterpene trachylobane (102)31>. 

The key steps in the synthesis of the stemodane-type diterpenoids are again the retroaldol-aldol procedure. This was best demonstrated by the rearrangement of the ketal (103) to the epimeric alcohol (104), upon treatment with acid, in 60%... 

The empimeric alcohol (107) again underwent the deprotection-retroaldol-aldol process to afford the product 108), which was used as a key intermediate in the total synthesis of 12-epi-lycopodine 109)37). 

A new method, reported by Pearlman (262), for the preparation of Woodward s key building block also constitutes a new synthesis of reserpine as well as deserpidine. In the key step of the synthesis an internal (2ir + 2-tt] photocycliza-tion of dienone 518 gave cyclobutane derivative 519 with the established stereochemistry. Methanolysis and subsequent peracid treatment of 520 yielded lactone ester 521. Repeated methanolysis and retroaldol fission of the cyclobutane... 

It has been demonstrated that beta-hydroxynitrosamines such as NDE1A may undergo retroaldol-type reactions in strongly alkaline medium to form nitrosamlnes of lower molecular weight (19, 20). In some cases the nitrosamlnes formed from the retroaldol reaction are more potent animal carcinogens than is NDE1A. 

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