INDEX synthetic routes

The biocatalytic reduction step B in synthetic route B demands more raw materials (mass index S , see equation (5.1)) and generates more waste (environmental factor , see equation (5.2)) as compared to reduction step C (Figure 5.1). Solvents used to perform the extraction of the product from the aqueous phase in reduction step B are denoted as auxiliaries in Figure 5.1. These solvents and the aqueous phase dominate the mass balances as well as the environmental scores in Figure 5.2 (M4, M8). 

Direct isolation of sufficient quantities of each metabolite for structural characterization, assay validation and pharmacological or toxicological testing from in vivo studies using biological specimens is, therefore, often impossible, particularly from dmgs with a low therapeutic index. Furthermore, many metabolites have structural modifications which are difficult to replicate by traditional chemical methods. A number of synthetic steps may be required to prepare such metabolites from the API, or, in the worst case, a completely new synthetic route may need to be developed. 

Investigation of the cytoxic agents of Stephania hernandifolia showed that both enantiomorphs and the racemic modification of tetrandrine (X) have significant in vivo activity against W 256. With a therapeutic index of greater than 2, ( )-tetrandrine warrants preclinical pharmacological study [53, 54]. A new synthetic route to the tetrandrine skeleton has been recently reported [55]. 

Once it is known which compounds need to be made, the next step is to study synthetic routes. Online literature searches may be carried out or reaction databases may be u.sed. Reaction indexing and synthesis planning are discus.sed elsewhere (see Reaction Classification Reaction Databases and Synthesis Design). There are many databases of known reactions. 

Definition Natural insecticide obtained by extraction of Chrysanthemum cinerariaefoiium flowers, or made synthetically Properties Vise, liq. si. sol. in water dens. 0.84 b.p. 170 C ( 0.1 mm) (dec.) ref. index 1.45 Toxicology ACGIH TLV/TWA 5 mg/m r LD50 (oral, rat) 200 mg/kg, (IP, rat) 200 mg/kg LDLo (oral, human) 1 g/kg, (IV, rat) 5 mg/kg poison by ing., IP, IV routes mod. toxic to humans by ing. allergen rapidly detoxified in Gl tract, but can cause Gl, respiratory, and CNS effects chronic exposure damages liver experimental reproductive effector TSCA listed Precaution Combustible exposed to heat or flame... 

The homopolymers of C4-C7 acrylates/methacrylates and Cg acrylate were found to be insoluble in the base oil even at very high temperatures (90°C) irrespective of the synthesis route. The additives increased the viscosity index of the untreated base oil from 90 to 135 with 1-4 wt% dose, which is comparable with the literature values for polymethacrylate additives in paraffin base oils (or with the synthetic polymethacrylate mineral oils with viscosities 11.4 and 78.1 cSt at 100 and 40°C, Table 8). 

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