Natural products suspensions

Acidic suspensions such as those produced by acid leaching often respond to natural products such as guar as well as nonionic polyacrylamides and anionic polyacrylamides containing sulfonic acid groups. 

Much effort has been directed at developing aqueous Diels-Alder reactions toward the syntheses of a variety of complex natural products. Grieco employed micellar catalysis and pure water as the solvent for the Diels-Alder reaction of dienecarboxylate with a variety of dienophiles. For example, when the Diels-Alder reaction in Scheme 12.3 was carried out in water, a higher reaction rate and reversal of the selectivity were observed, compared with the same reaction in a hydrocarbon solvent (Scheme 12.3).81 Similarly, the reaction of 2,6-dimethylbenzoquinone with sodium ( )-3,5-hexadienoate (generated in situ by the addition of 0.95 equiv sodium bicarbonate to a suspension of the precursor acid in water) proceeded for 1 hour to give a 77% yield of the adduct... 

Diosgenin (Fig. 4) is a steroid sapogenin produced by Dioscorea species. This natural product is used as a precursor for the commercial synthesis of medicinal steroids such as prednisolone, dexamethasone, norethisterone, and metenolone, among others. Microtuber-derived cell suspensions of Dioscorea doryophora were able to accumulate diosgenin at concentrations as high as 3.5% g dw. Embryogenic callus of Tribulus terrestris were also able to accumulate diosgenin (170.7 1.0 pg/g dw). ... 

Plant cell culture is useful in laboratory and in industry because it allows plant natural products to be produced in a relatively controlled manner, and provides a supply of plant material that is not affected by sourcing problems, such as environmental, seasonal, geographical, and political factors.Also, plant cell culture allows for the tweaking and rearrangement of secondary metabolite biochemical pathways in order to produce novel metabolites, and to increase target compound yields, as well as allowing derivatives to be formed by introduction of analogs of natural intermediates.Plant cell culture can be performed with callus and suspension cultures, as well as with shoot cultures and hairy root cultures. These latter two approaches are especially useful when a metabolite is found to be produced more readily in differentiated cells. 

Quinolizidine alkaloids (QA) are thought to be typical natural products of many Leguminosae (1-3) but a few isolated occurrences have been reported also in unrelated families, e.g. Chenopodiaceae ( 1 ), Berberidaceae ( ), Papaveraceae ( ), Scrophulariaceae ( ), Santalaceae ( ), Solanaceae ( ), and Ranunculaceae (J ). These observations could indicate that the genes for QA biosynthesis are probably not restricted to the Leguminosae but are widely distributed in the plant kingdom however, they are only rarely expressed in the other families. We could support this belief by recent experiments using plant cell suspension cultures. A short-term and transientQA formation could be detected after induction even in "QA-free" species, such as Daucus, Spinacia, Conium, and Symphytum (6). 

The enantioselective syntheses of (R)-oc-cuparenone and (S)-a-cuparenone, both of which are natural products from different sources, were also completed using the solid-state photodecarbonylation of diasteromerically pure difluorodioxaborinane ketones 192 and 194 (Scheme 2.47). The latter were prepared in two steps from 191, and irradiated as nanocrystalline suspensions to optimize the chemical yields of the transformation. The photoreaction of the optically pure ketones was 100% stereoselective with an isolated yield of 80%. The two natural products were obtained by simple acid removal of the chiral auxiliary. 

Typical suspension stabilizers for the production of EPS are water-soluble, surface-active macromolecules, such as poly (vinyl alcohol) (PVA), hydroxyethyl-cellulose (HEC) and polyvinylpyrrolidone (PVP), or natural products, such as gelatin [36-40], and insoluble inorganic powders, such as tricalcium phosphate (TCP), also called picketing stabilizer , mostly in combination with surfactants called extenders [33-35,44], or a combination of these [129]. The differences and specialties of these stabilizing mechanism are described briefly below ... 

A 35-year-old woman complained of nausea, fatigue, pruritus, dark urine, pale stools, and jaundice after taking a supplement containing chromium picohnate for weight loss (14). Infectious hepatitis was excluded and a liver biopsy was consistent with toxic liver damage. Hepatic chromium concentrations were more than 10 times normal. The chromium supplement was withdrawn and she received supportive treatment with a suspension containing natural products, colestyramine 1 g qds, and hydroxyzine 25 mg tds. She fully recovered in 3 months. 

Photodecarbonylation in the solid state allows to maintain stereochemical control. Thus, this highly stereospecific process can be exploited for the synthesis of enantiomerically pure natural products. As an example, the photodecarbonylation of an aqueous suspension of the diastereomeric difluoro-dioxaborinane complexes of p-keto-(5)-a-methylbenzylamide (1 and 2) was exploited for the synthesis of both enantiomers of a-cuparenone (3 and 4) with 100% stereoselectivity and in 80% yield (Scheme 2.2). ... 

Table I. Natural products accumulated in high levels by plant cell suspensions... 

Two major generalizations can be made regarding the production of natural products in callus and cell suspension cultures. First, in undifferentiated cells, growth is usually incompatible with the activation of a secondary pathway (9, ). Even in the case... 

However, most important is the addition of a preservative substance to prevent rnicrobial growth in the suspension. Preservatives are needed in most cases, since the suspension components, and mainly the flavors, constitute an excellent culture medium for the growth of microorganisms. Another source of contamination is the use of natural products (like gums and clays) to control the stability of the suspension. There are many acceptable preservatives to inhibit [he microbial growth in orally administered suspensions (see Ref. for an exhaus-... 

A breakthrough occurred, however, in the research on plant natural product biosynthesis when tissue and cell suspension cultures were developed by M.H. Zenk. ° Such cultures easily provided continuously fresh Rauvolfia cell material at kg level in a few weeks in cell culture laboratories where Erlenmeyer flasks were used for cell growth (Figure 2). 

It is noteworthy that prenylation of DHNA (V) occurs at carbon 3 rather than carbon 2 as occurs in vitamin K biosynthesis (vide supra). This is not only evident from the mode of incorporation of labelled -succinylbenzoic acid (II) into lucidin (XIII) but also from the finding that 2-methoxycarbonyl-3-prenyl-l,4-naphthoquinone (XIV)3 0 > 31 and the diglycoside of its hydroquinone (XV) are natural products occurring both in the intact plant ° and in cell suspension culture of G, mollugo. 

Ixtunasmaa M, Galambos J (1989) Indole alkaloid production in Catharanthus roseus cell suspension cultures. In Herz W, Grisebach H, Kirby GW, Tamm Ch (eds) Progress in the chemistry of organic natural products, vol 55. Springer, New York... 

The advantages of cell suspensions over callus culture are the following (a) they are less heterogeneous, and cell differentiation is less pronounced (b) they can be cultured in volumes of more than 1,500 L (c) they can be subjected to more stringent environmental controls and (d) manipulations for the production of natural products by feeding precursors are possible [12]. 

Mi Q, Lantvit D, Reyes-Lim E. Chai H, Zhao W, Lee IS, Peraza-Sanchez S, Ngassapa LBS, Riswan S, Hollingshead MG, Mayo JG, Farnsworth NR, Cordell GA, Kinghorn AD, Pezzuto JM (2002) Evaluation of the potential cancer chemotherapeutic efficacy of natural product isolates employing in vivo hollow fiber tests. J Nat Prod 65 842—850 Miguel MA, Barroso (1994) Accumulation of stress metabolites in cell suspension cultures of Hyoscyamus albus. Phytochenristry 35 371-375... 

Conventional anionic, cationic, amphoteric and nonionic surfactants are also used in cosmetic systems. Besides the synthetic surfactants that are used in preparing cosmetic systems such as emulsions, creams, suspensions, etc., several other naturally occurring materials have been introduced and there has been a trend in recent years to use such natural products more widely, in the belief that they are safer for application. 

---