A Hydroxyacid

As shown in equation 12, the chemistry of this developer s oxidation and decomposition has been found to be less simple than first envisioned. One oxidation product, tetramethyl succinic acid (18), is not found under normal circumstances. Instead, the products are the a-hydroxyacid (20) and the a-ketoacid (22). When silver bromide is the oxidant, only the two-electron oxidation and hydrolysis occur to give (20). When silver chloride is the oxidant, a four-electron oxidation can occur to give (22). In model experiments the hydroxyacid was not converted to the keto acid. Therefore, it seemed that the two-electron intermediate triketone hydrate (19) in the presence of a stronger oxidant would reduce more silver, possibly involving a species such as (21) as a likely reactive intermediate. This mechanism was verified experimentally, using a controlled, constant electrochemical potential. At potentials like that of silver chloride, four electrons were used at lower potentials only two were used (104). 

Figure A8.18 A racemic mixture of a-hydroxyacids (like L, D-lactate) can be transformed via the corresponding a-ketoacid (pyruvate) to the desired L-amino acid (L-alanine) with cofactor recycling.

Optically active tertiary a-hydroxyacids are useful starting materials for insect pheromones33, prostaglandin analogs34 and other important products. 

Racemic a-amino amides and a-hydroxy amides have been hydrolyzed enantio-selectively by amidases. Both L-selective and o-selective amidases are known. For example, a purified L-selective amidase from Ochrobactrum anthropi combines a very broad substrate specificity with a high enantioselectivity on a-hydrogen and a,a-disubstituted a-amino acid amides, a-hydroxyacid amides, and a-N-hydroxya-mino acid amides [102]. A racemase (a-amino-e-caprolactam racemase, EC 5.1.1.15) converts the o-aminopeptidase-catalyzed hydrolysis of a-amino acid amides into a DKR (Figure 6.38) [103]. 

Further experiments by Huber and Wachtershauser on chemoautotrophic biogenesis under hydrothermal conditions have shown that a number of a-amino acids and a-hydroxyacids could have been formed, subsequent to the binding of carbon (in the form of CO and CN ) to catalytically active transition metal precipitates. The general structure of such compounds is R-CHA-COOH, with R = H, CH3, C2H5 or HOCH2 and A = OH or NH2. 

Starting from ethanolamines 72, benzoxazepinones 73 [84—86], benzodiazepi-nones 74 [47, 86] and diazepanones 75 [47] have been produced depending on the starting carboxylic components. In the last case, classical Mitsunobu conditions gave unsatisfactory yields, and the conditions developed by Hanessian (SDI and NaH) were used instead. Using a-hydroxyacids 76, both benzoxazinones 69 [55] and benzoxazepinones 77 [55] have been accessed. The same compounds can also... 

Consider the reversible condensation polymerization reaction of a hydroxyacid A to form a polyester polymer,... 

Hydrazine hydrate reacts with a-hydroxyacids to give the A -aminodihydrotriazole which is diazotised with sodium nitrite in HCl to the 3,5-disubstituted triazole enantiomer (Scheme 24) <87H(26)989>. These triazoles were converted to macrocyclic derivatives (see Section 4.02.12.3). The ketals of a-oxoesters undergo the same series of reactions to give, after hydrolysis, the 3,5-dicarbonyl derivatives (Scheme 25) <92S398>. 

Problem 16.26 (a) When heated, 2 mol of an a-hydroxyacid (n = 0) lose 2 mol of H 0 to give a cyclic diester (a lactide). Give the structural formulas for two diastereomers obtained from lactic acid, CH,CHOHCOOH, and select the diastereomer which is not resolvable. (6) Synthesize lactic acid from CH,CHO. ... 

Ru/SILIA CAT TEMPO-MEDIATED OXIDATION OF ALKENES TO a-HYDROXYACIDS... 

The procedure is easily reproduced and can be applied to a variety of readily available olefins to afford valuable a-hydroxyacids (Table 6.3). The method offers a practical alternative to the use of cyanohydrins currently employed in industrial processes and further demonstrates the synthetic benefit of entrapping the TEMPO catalyst inside the nanocages of hydrophobized porous silica, where the radical catalytic molecules are highly protected from degradation. " Silia Cat TEMPO is a trademark of SdiCycle Inc., Quebec City, Canada. 

A naive look at the product suggests an oxidation to a ketone followed by a Baeyer-Villiger like reaction. The product is best explained by a fragmentation from an intermediate chromate ester, resulting on an aldehyde and a stabilized tertiary carbocation that is transformed into a tertiary alcohol by reaction with water. The hydroxyaldehyde so obtained may evolve to the final lactone either via a lactol or a hydroxyacid. 

Oxidation of the primary alcohol with PDC in DMF leads to a hydroxyacid that cyclizes ... 

In fact, natural tartaric acid (R,R) reacts easily at room temperature with phosphorus trichloride. The main products of the reaction are spirophosphoranes with a P-H bond formed from the a-hydroxyacid linkage (scheme (A)). 

Peptolide SDZ-214-103 is a cyclosporin-related undecapeptide lactone produced by the fungus Cylindrotrichum oligospermum [63], It differs from the cyclosporins mainly at position 8. Because of the presence of a hydroxyacid (D-Hiv) instead of an amino acid (D-alanine in the natural cyclosporins [82]), one ester bond results in the ring system. 

Bowser, P., Evenson, A., and Rawlings, A.V. 1997. Cosmetic Composition Containing a Lipid and a Hydroxyacid, European Patent Appl. EP058788B1. 

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