Homologation, addition

The metabolism of cinnamate and w-phenylalkane carboxylates has been studied in Rhodopseudomonaspalustris (Elder et al. 1992), and for growth with the higher homologs additional CO2 was necessary. The key degradative reaction was ()-oxidation, for compounds with chain lengths of three, five, and seven carbon atoms, benzoate was formed and further metabolized, but for the even-numbered compounds with four, six, and eight carbon atoms phenylacetate was a terminal metabolite. 

Often, esters are homologated by one carbon using the diazomethane-based Amdt-Eistert procedure. Kowalski homologation, addition of the inexpensive dibromomethane followed by -elimination, is a more scalable alternative. Timothy Gallagher of the University of Bristol recently reported (J. Org. Chem. 2004, 69, 4849) the use of Kowalski homologation to prepare P-amino esters from a-amino esters, including the conversion of 3 to 4. Note that the transformation can be carried out without protection of the OH, and that it proceeds without loss of stereochemical integrity. 

The surface tensions for solutions of organic compounds belonging to a homologous series, for example, R(CH2)nX, show certain regularities. Roughly, Traube [145] found that for each additional CH2 group, the concentration required to give a certain surface tension was reduced by a factor of 3. This rule is manifest in Fig. lll-15b the successive curves are displaced by nearly equal intervals of 0.5 on the log C scale. 

As discussed in Chapter III, the progression in adsoiptivities along a homologous series can be understood in terms of a constant increment of work of adsorption with each additional CH2 group. This is seen in self-assembling monolayers discussed in Section XI-IB. The film pressure r may be calculated from the adsorption isotherm by means of Eq. XI-7 as modified for adsorption from dilute solution ... 

The most general methods for the syntheses of 1,2-difunctional molecules are based on the oxidation of carbon-carbon multiple bonds (p. 117) and the opening of oxiranes by hetero atoms (p. 123fl.). There exist, however, also a few useful reactions in which an a - and a d -synthon or two r -synthons are combined. The classical polar reaction is the addition of cyanide anion to carbonyl groups, which leads to a-hydroxynitriles (cyanohydrins). It is used, for example, in Strecker s synthesis of amino acids and in the homologization of monosaccharides. The ff-hydroxy group of a nitrile can be easily substituted by various nucleophiles, the nitrile can be solvolyzed or reduced. Therefore a large variety of terminal difunctional molecules with one additional carbon atom can be made. Equally versatile are a-methylsulfinyl ketones (H.G. Hauthal, 1971 T. Durst, 1979 O. DeLucchi, 1991), which are available from acid chlorides or esters and the dimsyl anion. Carbanions of these compounds can also be used for the synthesis of 1,4-dicarbonyl compounds (p. 65f.). 

Table 2 3 lists the heats of combustion of several alkanes Unbranched alkanes have slightly higher heats of combustion than their 2 methyl branched isomers but the most important factor is the number of carbons The unbranched alkanes and the 2 methyl branched alkanes constitute two separate homologous senes (see Section 2 9) m which there is a regular increase of about 653 kJ/mol (156 kcal/mol) m the heat of combustion for each additional CH2 group... 

Prolactin-Like Proteins. A number of prolactin-like proteins (PLPs), which ate distinct from the PLs, have been identified in mminants and rodents (11,23). Several cDNA transcripts coding for PLPs in catde have been identified (23). These transcripts code for proteins which possess about 40% sequence homology with bovine PRL 60% if conservative substitutions ate considered. Three glycosylated PLPs, ie, PLP-A, -B, and -C, ate produced during pregnancy in the rat (11). Two additional prolactin-related molecules have been identified in the mouse (24,25), ie, proliferin [92769-12-5] (PLF) and PLF-related protein [98724-27-7]. These ate not found in other rodents and may be unique to the mouse. The functional roles of PLPs remain to be deterrnined. 

There are probably several processes that contribute to the total desensitization process and these may be directed homologously (to own receptor) or heterologously (to other receptor). Additionally, the induences may be directed at the receptor itself and affect only that receptor, ie, specific desensitization, or may affect other receptor processes as well, ie, nonspecific desensitization. 

Polymers from either of these homologous series can be made to predominate by usiag a small excess of the diamine or diacid, respectively. In addition to these linear polymers, cycHc oligomers are also formed, though ia this case n... 

There are many simple two-parameter equations for Hquid mixture constituents, including the Wilson (25), Margules (2,3,18), van Laar (3,26), nonrandom two-Hquid (NRTI.v) (27), and universal quasichemical (UNIQUAC) (28) equations. In the case of the NRTL model, one of the three adjustable parameters has been found to be relatively constant within some homologous series, so NRTL is essentially a two-parameter equation. The third parameter is usually treated as a constant which is set according to the type of chemical system (27). A third parameter for Wilson s equation has also been suggested for use with partially miscible systems (29,30,31). These equations all require experimental data to fit the adjustable constants. Simple equations of this type have the additional attraction of being useful for hand calculations. 

As a method of research, has been used high-performance liquid chromatography in reversed - phase regime (RP HPLC). The advantage of the present method is the following the additional information about AIST and FAS composition (homologous distribution) simple preparation of samples (dilution of a CS sample of in a mobile phase). 

An effective method for localizing causes of redox potentials is to plot the total backbone and side chain contributions to ( ) per residue for homologous proteins as functions of the residue number using a consensus sequence, with insertions treated by summing the contribution of the entire insertion as one residue. The results for homologous proteins should be examined for differences in the contributions to ( ) per residue that correlate with observed redox potential differences. These differences can then be correlated with any other sequence-redox potential data for proteins that lack crystal or NMR structures. In addition, any sequences of homologous proteins that lack both redox potentials and structures should be examined, because residues important in defining the redox potential are likely to have semi-sequence conservation of a few key amino acid types. 

Figure 2.19 Organization of polypeptide chains into domains. Small protein molecules like the epidermal growth factor, EGF, comprise only one domain. Others, like the serine proteinase chymotrypsin, are arranged in two domains that are required to form a functional unit (see Chapter 11). Many of the proteins that are involved in blood coagulation and fibrinolysis, such as urokinase, factor IX, and plasminogen, have long polypeptide chains that comprise different combinations of domains homologous to EGF and serine proteinases and, in addition, calcium-binding domains and Kringle domains.

A reaction related to the Michael addition reactions of enamines to unsaturated esters, which leads to S-ketoesters, is the reaction with 1-carb-ethoxy-l-cyanocyclopropane (318). This gives access to ketones substituted with the next higher homologous acid chain. 

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