The oxidative Weimberg pathway for the five-step pentose degradation to α-ketoglutarate is a key route for sustainable bioconversion of lignocellulosic biomass to added-value products and biofuels. The oxidative pathway from Caulobacter crescentus has been employed in in-vivo metabolic engineering with intact cells and in in-vitro enzyme cascades. The performance of such engineering approaches is often hampered by systems complexity, caused by non-linear kinetics and allosteric regulatory mechanisms. Here we report an iterative approach to construct and validate a quantitative model for the Weimberg pathway. Two sensitive points in pathway performance have been identified as follows: (1) product inhibition of the dehydrogenases (particularly in the absence of an efficient NAD + recycling mechanism) and (2) balancing the activities of the dehydratases. The resulting model is utilized to design enzyme cascades for optimized conversion and to analyse pathway performance in C. cresensus cellfree extracts.

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The enantiomers of eseroline bind to opiate receptors of rat brain membranes with equal affinities and show opiate agonist properties as inhibitors of adenylate cyclase in vitro. However, only (-)-eseroline shows potent narcotic agonist activity in vivo, similar to that of morphine. Neither (-)-noreseroline, (+)-eseroline, nor the open dihydroseco analogue (-)-8 shows analgetic effects in vivo. The structure of rubreserine being a resonance hybrid of an o-quinone with its zwitterionic mesomer is confirmed by solid-state X-ray diffraction analysis.

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I-Phenylethy1)-and (1 -iiaphthylethyl)ureas, obtained in the reaction of racemic amines with optically pure isocyanates, are separated and then decomposed in refluxing alcohols, to afford optically pure secondary amines and optically pure alkyl carbamates in quantitative yields. The scope of this fragmentation for the resolution of racemic mixtures of amines is illustrated by several examples of biologically important compounds. Carbamates obtained by this fragmentation can readily be recycled.(S)-5a having identical optical properties was prepared from amine (S)-6a and ethyl chloroformate [ 151. Scheme I also lists carbamates obtained in reactions described later. Reaction of 3 in refluxing propanol without addition of base also afforded (+)-mecamylamine ((+)-I), but at a slower rate.Reductive ring closure of oxindole (&)-7, prepared by the Juliun synthesis [4], was best accomplished with Na in EtOH and afforded 5-0-methyl-I-noreseroline ((f)-8; Scheme 2). Reaction of (f)-8 with isocyanate (S)-2a afforded after chromatographic separation of the mixture of diastereoisomers, the less polar urea 9 and the more polar urea 10 in 37 and 40% yield, respectively. Ureas 9 and 10 decomposed in refluxing 1~ sodium pentoxide in pentanol within 1 h, affording as basic materials the optically pure amines (+)- (non-crystalline) (+)-13 16En3 o CH,