Natural products, fluorinated structures

The search for nontoxic fluorinated surfactants is shifting from fully synthetic surfactants to perfluoroalkylated natural products. Fluorinated surfactants have been prepared from nontoxic biocompatible intermediates [42,117, 131-133]. Riess and his co-workers [131] at the University of Nice, France, have made perfluoroalkylated surfactants with a modular structure ... 

Difluoroenol ethers are synthetically equivalent to nucleophilic gem-difluoromethy-lene building blocks [24] which can be derivatized in their a-positions by a wide range of structures [25]. Similarly to their non-fluorinated analogs, they react with a variety of different electrophiles or radicals [26] and afford particularly convenient access to fluorinated analogs of natural products and other bioactive compounds. 

Halogen-containing compounds are not only produced by man, but also by Nature [1740-1742], A brominated indole derivative - Tyrian purple dye - was isolated from the mollusc Murex brandaris by the Phoenicians. Since that time, more than 1,000 halogenated natural products of various structural types have been isolated from sources such as bacteria, fungi, algae, higher plants, marine molluscs, insects, and mammals [1743], Whereas fluorinated and iodinated species are rather rare, chloro and bromo derivatives are found more often. The former are predominantly... 

From a practical viewpoint, the important question is, how does the toxicity of fluorinated surfactants compare to that of their hydrocarbon analogs A general statement cannot be made because the toxicity of fluorinated surfactants varies greatly with their structure. Some fluorinated surfactants derived from natural products, such as carbohydrates or lipids, are sufficiently biocompatible to be considered for intravascular use (see Section 10.4). Clearly, a fluorinated surfactant per se is not necessarily more toxic than a nonfluorinated surfactant. The toxici-ties of surfactants with con esponding structures have to be compared. 

The structures of all known fluorinated natural products are illustrated 1-6 apart from the series of long chain -fluoro fatty acids of which only the most abundant o-fluoro-oleic acid is shown. 

Generally, the fluorination products obtained could be classified into three groups - i) degradation products, ii) cyclisation products, iii) expected products - with the yields of the desired compounds ranging from fair to good, depending upon the structure of the acid skeleton, and the nature and position of the substituent (e.g., to block cyclisation by-product formation). 

As soon as chemists become interested in natural apatites, the problem with fluorine appears. When phosphate ores are treated the fluorine must be removed. On the other hand it is sometimes necessary to fluorinate calcium phosphates in the mineral part of calcified tissues. Obviously, in industry and medecine it is neces sary to know the mechanism of phosphate fluorination as well as the structure and the properties of products obtained. 

The fluorotelomer carboxylic acids (FTCAs) and fluorotelomer unsaturated carboxylic acids (FTUCAs) are degradation products of FTOHs with the general structure F(CF2) CH2CH00H and F(CF2) CHCOOH respectively, where usually n = 6, 8 or 10 (Table 3.1). Similar to FTOHs, FTCAs and FTUCAs are also named based on the ratio of fluorinated carbons to hydrogenated carbons in the molecule. Although the acid dissociation constants are not known for the FTCAs and the FTUCAs, it is assumed they will also dissociate in the natural environment ... 

Olean-12-enes are converted into the corresponding 12-chloro-derivatives, e.g. (121), on reaction with a gaseous mixture of nitrosyl chloride and chlorine in pyridine solution. This method has been used to separate natural mixtures of oleanenes and ursenes since the latter are inert under these conditions. The glycyrrhetic acid derivative (122) afforded the fluorinated product (123) on treatment with CF3OF at —70 °C. (123) decomposed readily in polar solvents to give a rearranged product which has been assigned the novel structure (124). 

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