A, 0-Hydroxy acid

Acetone cyanhydrin (a-Hydroxy sobutyronitrile) By this method, the nitrile of an a-hydroxy acid U necessarily obtained. 

Mandelic acid. This preparation is an example of the synthesis of an a-hydroxy acid by the cyanohydrin method. To avoid the use of the very volatile and extremely poisonous hquid hydrogen cyanide, the cyanohydrin (mandelonitrile) is prepared by treatment of the so um bisulphite addition compound of benzaldehj de (not isolated) with sodium cyanide ... 

Analysis The a-hydroxy acid can best be made from an aldehyde and, then we can cany on as usual with a 1,3-dicarbonyl disconnection ... 

Here is a more difficult example based also on a-hydroxy acids. Use the two phenyl groups as a clue for your first disconnetion in designing a synthesis for TM 135 ... 

A variety of a-amino acid derivatives, including the acids themselves, haUdes, esters, and amides can be transformed iato hydantoias by coadeasatioa with urea (67). a-Hydroxy acids and thek nitriles give a similar reaction (68) ... 

Reactions and Uses. The common reactions that a-hydroxy acids undergo such as self- or bimolecular esterification to oligomers or cycHc esters, hydrogenation, oxidation, etc, have been discussed in connection with lactic and hydroxyacetic acid. A reaction that is of value for the synthesis of higher aldehydes is decarbonylation under boiling sulfuric acid with loss of water. Since one carbon atom is lost in the process, the series of reactions may be used for stepwise degradation of a carbon chain. 

The two complementary functional groups that react to form condensation polymers may also occur in a single monomer, eg, a hydroxy acid,... 

Oxahc acid behaves as an a-hydroxy acid, yielding crystalline ammonium or potassium salts from either aqueous titanium(IV) solutions or tetraalkyl titanates (86). These are written as ... 

A broad selection of Ti(III) compounds coordinated to a-hydroxy acids, dibotic acids, and 8-hydroxyquinoline has been prepared by the reaction... 

In order to become useful dmg delivery devices, biodegradable polymers must be formable into desired shapes of appropriate size, have adequate dimensional stability and appropriate strength-loss characteristics, be completely biodegradable, and be sterilizahle (70). The polymers most often studied for biodegradable dmg delivery applications are carboxylic acid derivatives such as polyamides poly(a-hydroxy acids) such as poly(lactic acid) [26100-51-6] and poly(glycolic acid) [26124-68-5], cross-linked polyesters poly(orthoesters) poly anhydrides and poly(alkyl 2-cyanoacrylates). The relative stabiUty of hydrolytically labile linkages ia these polymers (70) is as follows ... 

The outstanding chemical property of cyanohydrins is the ready conversion to a-hydroxy acids and derivatives, especially a-amino and a,P-unsaturated acids. Because cyanohydrins are primarily used as chemical intermediates, data on production and prices are not usually pubUshed. The industrial significance of cyanohydrins is waning as more direct and efficient routes to the desired products are developed. Acetone cyanohydrin is the world s most prominent industrial cyanohydrin because it offers the main route to methyl methacrylate manufacture. 

Reaction of cyanohydrins with absolute ethanol in the presence of HCl yields the ethyl esters of a-hydroxy acids (3). A/-substituted amides can be synthesized by heating a cyanohydrin and an amine in water. Thus formaldehyde cyanohydrin and P-hydroxyethylamine lead to A/- (P-hydroxyethyl)hydroxyacetamide (4). 

Cyanohydrin Synthesis. Another synthetically useful enzyme that catalyzes carbon—carbon bond formation is oxynitnlase (EC 4.1.2.10). This enzyme catalyzes the addition of cyanides to various aldehydes that may come either in the form of hydrogen cyanide or acetone cyanohydrin (152—158) (Fig. 7). The reaction constitutes a convenient route for the preparation of a-hydroxy acids and P-amino alcohols. Acetone cyanohydrin [75-86-5] can also be used as the cyanide carrier, and is considered to be superior since it does not involve hazardous gaseous HCN and also virtually eliminates the spontaneous nonenzymatic reaction. (R)-oxynitrilase accepts aromatic (97a,b), straight- (97c,e), and branched-chain aUphatic aldehydes, converting them to (R)-cyanohydrins in very good yields and high enantiomeric purity (Table 10). 

Although alcohol dehydrogenases (ADH) also catalyze the oxidation of aldehydes to the corresponding acids, the rate of this reaction is significantly lower. The systems that combine ADH and aldehyde dehydrogenases (EC 1.2.1.5) (AldDH) are much more efficient. For example, HLAD catalyzes the enantioselective oxidation of a number of racemic 1,2-diols to L-a-hydroxy aldehydes which are further converted to L-a-hydroxy acids by AldDH (166). 

RUFF - FENTON Degradation Oxidative degradation of aldoses via a-hydroxy acids to lower chain aldoses. 

The 2-alkyl derivatives have been prepared to protect the stereogenic center of the a-hydroxy acid during alkylations. ... 

The use of carbohydrates as SM s has greatly expanded in recent years, and many cases have been summarized in a text by Hanessian.33 Several examples of such syntheses are indicated in Chart 15. Other commercially available chiral molecules such as a-amino acids or a-hydroxy acids have also been applied widely to the synthesis of chiral targets as illustrated by the last two cases in Chart 15. 

A wide vanety of nucleophiles, such as 1-alkylpyrroles, furans, thiophenls [51], phenols [52], anilmes [55, 54], indoles [55], CH-acidic compounds [56, 57], as well as organolithium [56], Gngnard [57, 59], organocadmiura, and organozmc compounds [56], undergo C-hydroxyalkylation with trifluoropynivates to yield derivatives of a-trifluoromethyi a-hydroxy acids. 

Oxazolidines are prepared to allow selective protection of the a- or co-COjU groups in aspartic and glutamic acids and a-hydroxy acids. 

From a hydroxy acid pivaldehyde, acid catalyst. ... 

Two reactions for the production of L-phenylalanine that can be performed particularly well in an enzyme membrane reactor (EMR) are shown in reaction 5 and 6. The recently discovered enzyme phenylalanine dehydrogenase plays an important role. As can be seen, the reactions are coenzyme dependent and the production of L-phenylalanine is by reductive animation of phenylpyruvic add. Electrons can be transported from formic add to phenylpyruvic add so that two substrates have to be used formic add and an a-keto add phenylpyruvic add (reaction 5). Also electrons can be transported from an a-hydroxy add to form phenylpyruvic add which can be aminated so that only one substrate has to be used a-hydroxy acid phenyllactic acid (reaction 6). 

Tin/lithium exchange on the a-alkoxy stannanes and subsequent addition of carbon dioxide led to optically active (7-protected a-hydroxy acids 18 with retention of configuration and without any loss of stereochemical information11. 

Drug treatment of photoaged skin can be categorized as antioxidants, a-hydroxy acids and topical retinoids. Of these three approaches only topical retinoids, particularly retinaldehyde and alWrans-retinoic acid, have a well documented ability to restorethe repair... 

---