Of -gabaculine

Hydroxylysine (328) was synthesized by chemoselective reaction of (Z)-4-acet-oxy-2-butenyl methyl carbonate (325) with two different nucleophiles first with At,(9-Boc-protected hydroxylamine (326) under neutral conditions and then with methyl (diphenylmethyleneamino)acetate (327) in the presence of BSA[202]. The primary allylic amine 331 is prepared by the highly selective monoallylation of 4,4 -dimethoxybenzhydrylamine (329). Deprotection of the allylated secondary amine 330 with 80% formic acid affords the primary ally-lamine 331. The reaction was applied to the total synthesis of gabaculine 332(203]. 

A synthetic isomer of gabaculine (VII Fig. 8) has similar biochemical activity in vitro and in vivo (21) to gabaculine (22). 

The remaining isomer of gabaculine (VIII Fig. 8) has recently been synthesized and awaits testing (23). 

This method has been used for synthesis (equation II) of ( )-gabaculine (5), a naturally occurring amino acid involved in metabolism of y-aminobutyric acid. An... 

Figure 2 Semi-log plot of the change in 6ABA-T activity in the presence of gabaculine, at 5X10 5M (two experiments) and 10 4M with time, showing first order kinetics.

Protective Effect of Gabaculine In Vivo Against Ethvl Aminooxvbutvrate (Compound 61... 

A particularly attractive starting material is the homochi-ral carboxylic acid derivative, obtained by conventional resolution. Esterification and then simple amine addition and oxidative decomplexation produces a precursor of (—)-gabaculine (Scheme 33). 

Matsui Y. and Deguchi T (1977) Effects of Gabaculine, a new potent inhibitor of gamma-ammobutyrate transaminase, on the bram gam-ma-aminobutyrate content and convulsions in mice Life Sci 20, 1291-1296... 

Wood J D and Kurylo E. (1984) Ammo acid content of nerve endings (synaptosomes) in different regions of brain Effects of gabaculine and isonicotinic acid hydrazide ] Neurochem 42, 420-425... 

Figure 3. Effects of gabaculine and dioxoheptanoic acid (DA) on efficacy of acifluorfen (AF) on cellular leakage as measured by electrolyte increase in the bathing media of cucumber cotyledon discs incubated in the various treatment solutions for 20 h in darkness before exposure to light (time 0).

FIGURE 1 The effect of gabaculine on Chi accumulation in pine seedlings growing for 14 days (A) in the light, and (B) in the dark. 

FIGURE 1. Effect of the supply of gabaculine on 5-ALAD activity. 

Leaves of gabaculine-treated plants appear pale yellow, and pigment analysis shows a specific effect only on chlorophyll and phytochrome. " Detailed analysis of photosynthetic pigments in gabaculine-treated plants shows a greater effect on chlorophyll biosynthesis in leaves which develop after treatment (Table 5.1). Leaf expansion continues in the absence of chlorophyll biosynthesis, and after seven days, once expansion is complete. 

Gabaculine-treated chlorophyll-deficient leaves respire normally, and there is normal cytochrome c oxidase in isolated mitochondria, providing evidence for the C5 pathway in plastids and the Shemin pathway in mitochondria and indicating the specific effect of gabaculine on the plastid... 

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