92351-94-5Relevant articles and documents
Stereochemistry and Mechanisms of the 3-Carboxymuconate Fungal Pathway in Neurospora SY4a
Hill, Robert A.,Kirby, Gordon W.,O'Loughlin Gary J.,Robins, David J.
, p. 1967 - 1972 (2007/10/02)
The cyclisation of cis,cis-3-carboxymuconic acid 2, catalysed by cycloisomerase enzyme of Neurospora crassa SY4a, has been shown to occur by syn addition of the 1-carboxy group to the 4,5-double bond to give (S)-(-)-carboxymuconolactone 3.Thus, the absolute configuration of the lactone 3 was determined by ozonolysis to give (S)-malic(L-malic) acid.Furthermore, incubation of trisodium cis,cis-3-carboxy-5-deuteriomuconate 9 then ozonolysis of the derived lactone 28 gave (2S,3S)-3-deuteriomalic acid 29.This evidence for syn addition was confirmed by a complementary incubation of undedeuteriated 3-carboxymuconate in deuterium oxide, giving the lactone 31 and hence (2S,3R)-3-deuteriomalic acid 32. The degradation of 3-carboxymuconolactone 3 by multifunctional enzyme complex of Neurospora, to give 3-oxoadipic acid 5, has been studied with the deuteriated trisodium muconates 27, 14 and 20.The overall transformation has been found to involve an intramolecular, suprafacial 1,3-shift of hydrogen (or deuterium) from C-4 in the lactone to C-5 in the oxoadipic acid.The location and stereochemistry of deuterium in the oxoadipic acids 44 and 45 were esteblished by conversion of these acids into the optically active 2-deuteriosuccinic acids 46 and 47, respectively.The 1,3-shift provides compelling eveidence for the formation of the enol lactone 4 as an enzyme-bound intermediate.Successive enzymic hydrolysis and decarboxylation would then complete the biosynthesis of 3-oxoadipic acid 5.
