Chain homologation

The classic method for controlling stereochemistry is to perform reactions on cyclic substrates. A rather lengthy but nonetheless efficient example in the prostaglandin field uses bicyclic structures for this purpose. Bisacetic acid derivative S is available in five steps from Diels-Alder reaction of trans-piperylene and maleic anhydride followed by side-chain homologation. Bromolactonization locks the molecule as bicyclic intermediate Esterification, reductive dehalogen-... 

A. Mixture of carbon chain homologs and phenyl isomers 110... 

A. Mixture of Carbon Chain Homologs and Phenyl Isomers... 

Before considering LAS in mixtures with other surfactants it must be noted that LAS itself is a mixture of many phenyl isomers and carbon chain homologs. 

Carbon chain homolog distribution is nearly always the most important factor in determining performance and formulation characteristics of LAS [19]. Phenyl isomer distribution and dialkyltetralinsulfonate content have their greatest impact on the formulation characteristics of LAS in liquid detergents. 

Since commercial products are mixtures of homologs they are more soluble than the pure components due to the solubilizing effect of the short-chain homologs as mentioned above. Table 5 shows the solubility in water of calcium salts of alcohol sulfates at 25°C [73]. 

Growth-Arrest-Specific protein 2 Domain Gastrin/cholecystokinin/caerulein family Dynamin GTPase effector domain Gelsolin homology domain G protein y subunit-like motifs Glycoprotein hormone a chain homologs... 

Scheme 2.22 Living chain homologation using two complementary immobilized catalysts.

Reactions of alkane-1,1-dicarboxylic acids, e.g. la, alkane-1,4-dicarboxylic acids, e.g. lb, and their longer-chain homologs with sulfur tetrafluoride afford mixtures of bis(trifluoromethyl)-alkanes, bis(pentafluoroalkyl) ethers and small amounts of polyethers.118 Total yields, generally, decrease with increasing length of the carbon chain and in the presence of C = C bonds. 

Most of the investigations into disproportionation reactions have mainly concentrated on chlorofiuoro derivatives of methane and ethane. When trichlorofluoromethane is refluxed with aluminum trichloride or aluminum tribromide, dichlorodifluoromethane and carbon tetrachloride are obtained. Dichlorofluoromethane yields chlorodifiuoromethane and chloroform chlorofiuoro derivatives of ethane and longer chain homologs exhibit a tendency towards isomerization as well as disproportionation, i.e. intramolecular halogen atom exchange. In this case, both types of reaction take place simultaneously. In other words, disproportionation of l,l,2-triehloro-1.2,2-trifiuoroethane (1) forms l,l,1.2-tetrachloro-2,2-difluoroethane (2) and... 

Austin 1930 Molecular weight Long-chain homologs... 

Flory, Vrij 1963 Entropy Rln (no. of carbons in chain) Homologous series... 

Flory, P. and A. Vrij. 1963. Melting Points of Linear-Chain Homologs. The Normal Paraffin Hydrocarbons. J. Am. Chem. Soc. 85, 3548. 

This commonly observed trend is attributed to the lipophilicity of alkyl chains and its impact on the ability of molecules to diffuse across membranes. Short alkyl chains do not sufficiently contribute to the lipophilicity of a molecule, and the compound cannot effectively cross the nonpolar interior of a membrane. If the chain is too long, the compound becomes too lipophilic, readily enters membranes, and never leaves. Chain homologation probes for the happy medium. 

The following Case Studies show several examples of isosteres and bioisosteres in use. The story of the development of cimetidine also demonstrates the use of chain homologation. 

One of alternative syntheses of allylic boranes is their synthesis via hydroboration of alkynes followed by one carbon chain homologation using thiomethoxymethylli-thium. This provides exclusive placement of boron atom at the terminal position as shown in Eq. 44 97). 

Figure 8 Allowed areas of the steric map for various terminally blocked amino acid residues X.45 In area 0, no conformations are allowed. Conformations in areas 1 to 4 are allowed for X = glycine, in areas 2 to 4 for X = alanine, in areas 3 to 4 for higher straight-chain homologs, whereas only area 4 is allowed for X = valine or isoleucine. The circles marked R and L indicate the locations of the standard right-and left-handed a helices on the steric map.

Jayasinghe, L. R. Datta, A. Ali, S. M. Zygmunt, J. Vander Velde, D. G. Georg, G. I. Structure-activity studies of antitumor taxanes synthesis of novel C-13 side chain homologated taxol and taxotere analogs. J. Med. Chem., 1994, 37 2981-2984. 

Figure 6. A 3u and a 12/10 helix, a parallel and an antiparallel sheet (with hair-pin turn) and a stack (clockwise from top left) formed by p-peptides consisting exclusively of simple open-chain homologated a-amino-acid residues (Ala, Val, Leu, Lys side chains) and of a-Methyl-P-homo-Ala and Leu residues [12,21,36].

Direct chlorination of acetic acid in the presence of a small quantity of red phosphorus is a standard procedure for the preparation of chloro-acetic acid however, similar treatment of its straight-chain homologs gives complex mixtures of halogenated acids. Substitution by chlorine in a btanched-chain acid such as isovaleric acid occurs largely at the tertiary hydrogen. The peroxide-catalyzed chlorination of aliphatic acids... 

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