Vindoline microbial transformation

Earlier biotransformation studies with vindoline were reported from the Eli Lilly Laboratories (166-168), and microbial transformation products included N-demethylvindoline (48), deacetylvindoline (49), and a structurally novel com-... 

The microbial transformations of vindoline and its derivatives have been further examined. Human caeruloplasmin and laccases of Polyporus anceps and Rhus vernicifera converted vindoline (44) into the known enamine 270 and the dimer 266 (201), which have been encountered in previous microbiological studies on vindoline. The dimer 266 is also formed by the action of horseradish peroxidase on vindoline (202). 

The microbial transformation of vindoline by means of Streptomyces griseus gives dihydrovindoline ether (previously obtained) and a novel vindoline dimer (265). ... 

Recent work in our laboratories has confirmed the existence of a similar pathway in the oxidation of vindoline in mammals (777). The availability of compounds such as 59 as analytical standards, along with published mass spectral and NMR spectral properties of this compound, served to facilitate identification of metabolites formed in mammalian liver microsome incubations. Two compounds are produced during incubations with mouse liver microsome preparations 17-deacetylvindoline, and the dihydrovindoline ether dimer 59. Both compounds were isolated and completely characterized by spectral comparison to authentic standards. This work emphasizes the prospective value of microbial and enzymatic transformation studies in predicting pathways of metabolism in mammalian systems. This work would also suggest the involvement of cytochrome P-450 enzyme system(s) in the oxidation process. Whether the first steps involve direct introduction of molecular oxygen at position 3 of vindoline or an initial abstraction of electrons, as in Scheme 15, remains unknown. The establishment of a metabolic pathway in mammals, identical to those found in Strep-tomycetes, with copper oxidases and peroxidases again confirms the prospective value of the microbial models of mammalian metabolism concept. 

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See also in sourсe #XX -- [ , , , , , , , , ]

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