2.4- Dihydroxybutyrate

Several years ago, we introduced a method for the preparation of optically pure 3,4-dihydroxybutyric acids and their y-lactones based on the alkaline oxidation of 4-linked hexoses (2-4). 

Chiral 3-carbon synthons from optically pure 3,4-dihydroxybutyric acids. 

The general availability of optically pure 3,4-dihydroxybutyric acids has opened up several new routes to chiral 3-carbon fragments with a wealth of functionality. The (S)- and (R)-enantiomers of 3-amino-1,2-dihydroxypropane (15 and 19 respectively) are among the most useful chiral 3-carbon synthons. 

Cativiela, C., Diaz-de-Villegas, M. D., Galvez, J. A., Garcia, J. L. Diastereoselective Strecker reaction of D-glyceraldehyde derivatives. A novel route to (2S,3S)- and (2R,3S)-2-amino-3,4-dihydroxybutyric acid. Tetrahedron 1996, 52, 9563-9574. 

Dhamankar, H., Tarasova, Y., Martin, C.H., and Prather, K.L.J. (2014) Engineering E. coli for the biosynthesis of 3-hydroxy-y-butyrolactone (3HBL) and 3,4-dihydroxybutyric acid (3,4-DHBA) as value-added chemicals from glucose as a sole carbon source. Metab. Eng.,... 

Four-carbon Meta accharinic Acid DL-(3-Deoxytetronic acid), [dl-(2,4-dihydroxybutyric acid)] ... 

The acid components required for the synthesis of the ester alkaloids, (+)-trachelanthic and viridifloric acids, were synthesised by stereospecific routes, since the relative stereochemistry of the asymmetric centres in these acids was still uncertain. Eventually they were obtained by appropriate stereospecific icis or trans) hydroxylation of trans-2-isopropylcrotonic acid (34), and its cis-isomer obtained by photochemical isomerisation. After resolution, (+)-trachelanthic acid was identified as the t/irco-2-isopropyl-2,3-dihydroxybutyric acid (35) the corresponding erythro-isomet was identified as viridifloric acid. 

That these two acids are identical has not been established. Macro-tomine gives trachelanthamidine and 2,3-dihydroxybutyric acid (quinine salt, mp 173°-174°, [a] j —104.4°) with sodium hydroxide at 100°C. The same acid forms less readily from heliosupine (149), and a similar structure has been assigned to the acid in the optically inactive cynoglossophine (150). 

We will focus here on a simple hydroxylation process of enolate radicals generated from ester enolates via SET oxidation. Ferrocenium ion was used as the oxidizing agent, and the radical intermediate was trapped with TEMPO [48]. In a second step, the alkoxylamine was reduced with zinc to the corresponding a-hydroxyester. The hydroxylation of ethyl 3-hydroxybutyrate gave the ethyl 2,3-dihydroxybutyrate with moderate stereocontrol (Scheme 17). 

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