Solubility of starting materials

The most frequendy used technique to shift the equilibrium toward peptide synthesis is based on differences in solubility of starting materials and products. Introduction of suitable apolar protective groups or increase of ionic strength decreases the product solubility to an extent that often allows nearly quantitative conversions. Another solubility-controlled technique is based on introduction of a water-immiscible solvent to give a two-phase system. Products preferentially partition away from the reaction medium thereby shifting the equilibrium toward peptide synthesis. 

In the laboratory, THF is the solvent of choice for generating metalated aromatic species. Diethyl ether is highly flammable, more toxic, and prone to the formation of peroxides [7]. Aromatic hydrocarbons can be used however, toluene is relatively easily lithiated, and benzene is toxic and cannot be used at low temperatures. The obvious trade-off of using a hydrocarbon as solvent is the lower solubility of starting materials as well as of the organolithium intermediate. The presence of excess... 

The starting material is moderately soluble in hot chloroform, while 2-hydroxyisophthalic acid is quite insoluble. Fractional crystallization from water, an alternative method suggested for the separation of starting material, has been found by the submitters to be unsuccessful. 

Currently, we can produce 1.5 g of GUS protein and 0.5 g of HSA per kg of seeds. These levels correspond to 13.5kg and 4.5 kg production yields per year, respectively. Expression levels are indicated as a weight per weight of starting material (dry seeds) because the sprout fresh weight and total soluble protein content varies depending on cultivation time and conditions. 

Preparative photolysis of AETSAPPE (0.25 M aqueous solution) at 254 nm (Rayonet reactor) resulted in the formation of the disulfide product 2-amino(2-hydroxy-3-(phenyl ether) propyl) ether disulfide (AHPEPED) as the primary photoproduct Photolysis of AETSAPPE at 254 nm (isolated line of medium pressure mercury lamp) resulted in rapid initial loss of starting material accompanied by formation (analyzed by HPLC) of AHPEPED (Figure 12a and 12b) (Scheme IV). Similar results were obtained for photolysis- at 280 nm. Quantum yields for disappearance of AETSAPPE and formation of AHPEPED at 254 nm and 280 nm are given in Table I. The photolytic decomposition of AETSAPPE in water was also accomplished by sensitization ( x =366 nm) with (4-benzoylbenzyl) trimethylammonium chloride (BTC), a water soluble benzophenone type triplet sensitizer. The quantum yield for the sensitized disappearance (Table I) is comparable to the results for direct photolysis (unfortunately, due to experimental complications we did not measure the quantum yield for AHPEPED formation). These results indicate that direct photolysis of AETSAPPE probably proceeds from a triplet state. 

Normally synthetic reactions for modification of these natural polymers have been conducted heterogeneously. In the absence of acceptable solvents, characterization of starting materials is difficult and reaction yields are often low due to unfavorable kinetics. Only in those cases in which the substituted products were soluble, have polymer structures been readily identifiable by instrumental analysis.. . ... 

C-C bond formation using the Heck reaction allows the introduction of functional groups to obtain new organic structures on solid supports. This reaction between an alkene with an alkenyl or an aryl halide has been widely employed in various in-tra- and inter-molecular versions on solid-phase because of the readily accessibility of starting materials. The Heck reaction was performed on immobilized aryl or alkenyl halides with soluble alkenes and vice versa (Scheme 3.11). 

An even more intimate mixture of starting materials can be made by the coprecipitation of solids. A stoichiometric mixture of soluble salts of the metal ions is dissolved and then precipitated as hydroxides, citrates, oxalates, or formates. This mixture is filtered, dried, and then heated to give the final product. 

Due to the low solubility of cobalt(II) fluoride in most solvents, formation of cobalt fluoro N-donor complexes (which are the only low-valent cobalt fluorides which are reliably reported) features a variety of starting materials. A common theme that runs throughout this work has been the use of [Co(BF4)2] as the fluoride source, and the subsequent controlled decomposition to obtain a metal-bound fluoride. This has been done, for example, with tris- (3,5-dimethyl-pyrazol-l-yl)methyl amine (amtd) to give [M2(amtd)2F(BF4)3(EtOH)Y(H20)] (M = Co, Cu, Zn x = 0-1.5, y = 1-2). The cobalt complex has been structurally characterised by X-ray diffraction [Fig. 3] [57]. Similarly, the combination of [M(BF4)2] (M = Mn, Co, Ni), [M(N03)2], NH4(NCS) and 3,5-diethyl-1,2,4-triazole (detrH) produces... 

The preparations described below represent a balance among the several rate factors, the availability of starting materials, and the over-all convenience of the procedure. In particular, the use of sodium tetrahydroborate instead of lithium tetrahydroborate eliminates both the handling of a pyrophor and the contamination of the products with ether-soluble lithium salts. 

Solubility ratios of the desirable compound over the undesirable impurities and the purity of starting material limit the maximum theoretical yield achievable with acceptable purity for the desirable compound. Continuing the previous example, let us assume that the crude starting material contains 15 wt% of one key impurity and the solubility of this impurity is identical to the solubihty of the desirable compound. If we charge 100 gm of crude solid, which has 85 gm of desired compound and 15 gm of impurity, into 1 liter of solvent, the final crystallized product will contain... 

Figure 2. pH-solubility profiles of a new chemical entity E2050 constructed with different amounts of starting material as the Di-HCl salt. 

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