Tiglyl

Figure 30-21. Subsequent catabolism of the tiglyl-CoA formed from L-isoleucine.

Two acyl-CoA amino acid A-acyltransferases have been purified from liver mitochondria of cattle, Rhesus monkeys, and humans. One is a benzoyltransferase CoA that utilizes benzyl-CoA, isovaleryl-CoA, and tiglyl-CoA, but not phenylacetyl CoA, malonyl-CoA, or indolacetyl-CoA. The other is a phenylacetyl transferase that utilizes phenylacetyl-CoA and indolacetyl-CoA but is inactive toward benzoyl-CoA. Neither is specific for glycine, as had been supposed from studies using less defined systems both also utilize asparagine and glutamine, although at lesser rates than glycine. 

This methodology has been expanded to geranyl methyl carbonate for the synthesis of the vitamin E nucleus, and to tiglyl methyl carbonate for the synthesis of (—)-calanolide A and B. In the latter example, the anthracenyldiamine -based ligand was required for optimum selectivity. The synthesis of (—)-aflatoxin B lactone utilizes a dynamic kinetic asymmetric transformation, whereby a suitably functionalized phenol reacts with a racemic 5-acyloxy-2-(5//)-furanone to provide a single product in 89% yield. One final example of phenol as a nucleophile is for the deracemization of Baylis-Hillman adducts." ... 

Deamination to a-keto-P-methylvalerate oxidative decarboxylation to a-methylbutyryl CoA oxidation to tiglyl CoA hydration, oxidation and thiolysis yields acetyl CoA and propionyl CoA propionyl CoA to succinyl CoA. 

In known metabolic states and disorders, the nature of metabolites excreted at abnormal levels has been identified by GC-MS. Examples of this are adipic and suberic acids found in urine from ketotic patients [347], 2-hydroxybutyric acid from patients with lactic acidosis [348], and methylcitric acid (2-hydroxybutan-l,2,3-tricarboxylic acid) [349] in a case of propionic acidemia [350,351]. In the latter instance, the methylcitric acid is thought to be due to the condensation of accumulated propionyl CoA with oxaloacetate [349]. Increased amounts of odd-numbered fatty acids present in the tissues of these patients due to the involvement of the propionyl CoA in fatty acid synthesis, have also been characterised [278]. A deficiency in a-methylacetoacetyl CoA thiolase enzyme in the isoleucine pathway prevents the conversion of a-methylacetoacetyl CoA to propionyl CoA and acetyl CoA [352,353]. The resultant urinary excretion of large amounts of 2-hydroxy-3-methylbutanoic acid (a-methyl-/3-hydroxybutyric acid) and an excess of a-methylacetoacetate and often tiglyl glycine are readily detected and identified by GC-MS. 

Meteloidine (C13H21O4N) (203), occurs to the extent of 0.07% along with 1-scopolamine and atropine in Datura meteloides. This alkaloid is optically inactive and resisted all attempts at resolution (212). It is a tiglyl ester of an alkamine, teloidine, and its saponification (Ba(OH)j) may be conveniently expressed as follows ... 

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