Gabaculine synthesis

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]. 

The regioselectivity during hydride abstraction afforded by an ester substituent attached to cyclohexa-diene has also been exploited for total synthesis. The synthesis of (+)- and (-)-gabaculine in homochiral... 

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... 

Whereas ammonia is an unsuitable nucleophile towards 7r-allylpalladium complexes, primary amines often participate well. Benzylamine and 4,4 -dimethoxybenzhydrylamine are especially useful, since subsequent removal of the benzylic substituents permits their use as ammonia equivalents. Such a deblocking procedure was used in a short synthesis of the enzyme inhibitor gabaculine from amino ester 1118. An allyl carbonate can be successfully employed as a substrate for palladium(0)-catalyzed animation to give 1219,20, but experimental difficulties have been experienced with a structurally similar carbonate9. As shown by the formation of 1016 and by the partial production of 13 prior to basic hydrolysis16, additional attack on an ester function may occur. Amino alcohols 13, formed with complete regioselectivity due to steric reasons, have been efficiently converted into isoquinuclidines16. 

Regulation of development, with the assembly of multimeric complexes, often requires the integration of diverse biosynthetic pathways. Thylakoid biogenesis is a notable example, since it requires cytosolic and chloroplastic protein synthesis, chlorophyll (Chi) production, iron-sulfur center biosynthesis, etc. Two biochemical probes, gabaculine (3-amino-2,3-dihydro-benzoic acid) and AHA (4-amino-hexynoic acid), permit the study of thylakoid assembly when one of these pathways, Chi biogenesis, is restricted by inhibition at the level of aminolevulinic acid synthesis (1,3). 

Knowledge of the inhibition of ALA synthesis by gabaculine provoked Flint to attempt to design some further inhibitors of ALA synthesis and evaluate their potential as herbicides. Some proved to be potent inhibitors and active herbicides. To date, no commercialization of ALA synthesis inhibitors has occurred, but these inhibitors have been successfully used to probe and gain information on the biosynthesis of ALA and tetrapyrroles in plants. 

Alonso, E., and V. Rubio, 1989. Participation of ornithine aminotransferase in the synthesis and catabolism of ornithine in mice - studies using gabaculine and arginine deprivation. Biochem. J. 259,131-138. 

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