GABOB

The silatropic ene pathway, that is, direct silyl transfer from an silyl enol ether to an aldehyde, may be involved as a possible mechanism in the Mukaiyama aldol-type reaction. Indeed, ab initio calculations show that the silatropic ene pathway involving the cyclic (boat and chair) transition states for the BH3-promoted aldol reaction of the trihydrosilyl enol ether derived from acetaldehyde with formaldehyde is favored [60], Recently, we have reported the possible intervention of a silatropic ene pathway in the catalytic asymmetric aldol-type reaction of silyl enol ethers of thioesters [61 ]. Chlorine- and amine-containing products thus obtained are useful intermediates for the synthesis of carnitine and GABOB (Scheme 8C.26) [62],... 

M. E. Jung and T. Shaw, Total synthesis of (R)-glycerol acetonide and the antiepileptic and hypotensive drug (-)-y-amino-/l-hydroxybutyric acid (GABOB) use of vitamin C as a chiral starting material, J. Am. Chem. Soc., 102 (1980) 6304-6313. 

A new class of GABAb receptor modulators was discovered simultaneously by replacing the carboxylic acid groups of GABA, GABOB (i.e. y-amino-p-hydroxy-... 

C4 chiral synthetic units are also important for the syntheses of pharmaceuticals and their intermediates. For example, optically active 4-chloro-3-hydroxybutyrate (CHB) and 4-chloro-3-hydroxybutyronitrile (BN) are key compounds as C4 chiral building blocks for the syntheses of L-carnitine [16], l-GABOB [17], / -hydroxybuty-ric acid, 3-hydroxy-y-butyrolactone, and 4-hydroxy-2-pyrrolidone. Recently, CHB has been reported as being used for synthesizing an intermediate for HMG-CoA reductase inhibitor for hyperlipidemia (Fig. 11) [18]. 

Enantioselective aUylboration (R)-y-amino-fi-hydroxybutyric acid.1 Reaction of bromoacctaldehyde with 1 in ether at —100° provides the (R)-bromohydrin 2 in 89% ee ( 50% yield), which is converted to the (R)-epoxide 3 on treatment with KOH. This epoxide is a precursor to 4, (R)-(-) y-amino-/3-hydroxybutyric acid (GABOB), a ncuromodulator. 

The use of bromodeoxy lactones as chiral building blocks for the stereoselective preparation of natural compounds was also explored. Thus, both (5)-and (J )-carnitine, (S)- and (J )-4-amino-3-hydroxybutanoic acid (GABOB), compounds of high relevance for the central nervous system, as well as musc-aridine and 6-deoxyascorbic acid, were prepared by simple transformations of the bromodeoxy aldonolactones. 

K. Bock, I. Lundt, and C. Pedersen, Synthesis of S- and R-4-amino-3-hydroxybutyric acid (GABOB) and S- and R-camitine from arabinose or ascorbic acid, Acta Chem. Scand, B37 (1983) 341-344. 

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