Raucaffricine

Ruppert, M., Panjikar, S., Barleben, L. and Stockigt, J. 2006. Heterologous expression, purification, crystallization and primary X-ray analysis of raucaffricine glu-cosidase, a plant enzyme specifically involved in Rauvolfia alkaloid biosynthesis. Acta Crystallographica Section F-Structural Biology and Crystallization Communications, 62 257-260. 

Significant efforts to select lines of R. serpentina that accumulate high levels of a heart drug known as ajmaline have failed since they tend to accumulate raucaffricine, the glucoside of vomilenine (Fig. 8.10). Cell cultures contain both a... 

WARZECHA, H., OBITZ, P., STOECKIGT, J., Purification, partial amino acid sequence and structure of the product raucaffricine-0- 3-D-glucosidase from plant cell cultures of Rauwolfia serpentina., Phytochemistry, 1999, 54,657-666. 

R. serpentina cell cultures, raucaffricine levels amounted to 1.2 g/L medium, whereas ajmaline levels reached only 0.3 g/L medium (Schtibel et al, 1986). It is interesting to note that raucaffricine is a fypical constituent of R. cajfra, but has not been isolated from other Rauvolfia species. However, in Rauvolfia cell cultures the compound is found in all species tested, with a maximum yield in R. serpentina. In other words, under these growth conditions, the pathway to ajmaline appears to have become deregulated. 

Schiibel, H., Stockigt, J., Feicht, R. and Simon, H. (1986) Partial purification and characterisation of raucaffricine fJ-D-glucosidase from plant cell suspension cultures of Rauwolfia serpentina Benth. Helv. Chim. Acta, 69, 538-47. 

For the revision of the original structure given for raucaffricine (44), see reference (155b). 

N(l)-Demethylseredamine32 (24a) has been identified as a constituent of Rauwolfia sumatrana Jack as well as sandwicine (24b), isosandwicine (24c) has been isolated from R. vomitoria,33 and vinorine (24d)34 and majoridine (24e)35 from Vinca species. Raucaffricine (24f)36 from R. caffra is the first of the ajmaline... 

For R. canescens cell cultures it was reported that elicitation results in a transient increase of jasmonic acid. The addition of methyl jasmonate to these cultures resulted in an almost 30-fold increase of the accumulation of the indole alkaloid raucaffricine (344). 

SG and raucaffricine glucosidase share a high degree of structural similarity. Both are members of the GH-1 superfamily. They are illustrated and compared in the paragraph on raucaffricine glucosidase later in Section 4.3.2. 

An important one-step side route originates from vomilenine (20) resulting in the formation of the glucoalkaloid raucaffricine (vomilenine 21-O-p-D-glucopyranoside, 30), which is catalyzed by vomilenine glucosyltransferase (Figure 25). It is the most productive side reaction of the AP, because... 

There is a reverse reaction of VGT, catalyzed by the enzyme raucaffricine... 

The glucoalkaloid raucaffricine has been reported to be synthesized in Rau-volfia cell cultures as the major alkaloid. Isolation and cloning of the cDNA of raucaffricine glucosidase enabled overexpression of the recombinant enzyme which can be prepared in applicable amounts and used efficiently in chemo-enzymatic routes. 

In the third strategy raucaffricine (30) is first deacetylated under basic conditions. The formed glucoaldehyde 99 isomerizes spontaneously to product 100, then giving the aldehyde 101 in the presence of RG (Figure 43). 

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