Cyclopropane acidity

Ketone (4) looks very difficult to disconnect. With a chain extension in mind, disconnection to acid (5) and removal of CHg gives an easily made cyclopropane acid (6). 

The Tafel rearrangement only occurs in acid medium. Simultaneous reduction of both carbonyl groups leads to interaction and formation of a cyclopropane. Acid catalysed cyclopropane ring opening follows to yield an a-diketone 28 which undergoes the electrochemical Clemmensen reduction step to the hydrocarbon. Side products include the two monoketones derived by partial deoxygenation of the a-diketone and the secondary alcohols from reduction of these raonoketones. Separate experiments show that the a-diketone 28 can be reduced to the hydrocarbon. 

By heating the pyrazolene formed by the addition of d iazoacetlc ester to ltaconlc ester a tribaelc cyclopropane acid of the following formula results CH - 0 - CH -COOH. No x / nCO0H CH-COCH... 

The methods of preparation of i..ost cyclopropane acids involve first the preparation of t e cyclic ester and subsequent hydrolysis to the free acid. That such hydrolysis cyclic structure has been seen to be true in all tne cases thus ar exctmined i o exceptions to tnis rule will now be studied,for they are botn 1,1,2,3 compounds. Aconitic ester and diazoacetic ester give by the usual reactxons a cyclopropane ester as follows ... 

This cyclopropane acid is i. uch lees reactive towards addition reagents than any of the ring compounds thus far dealt with. It is not attacked bji cold saturated aqueous liydrcfcroi.ic acia (although it dissolves in it) and is lijcewise uhreactive towards bromine in... 

Dunnick and O Leary [149] examined the lipid composition of a number of bacteria both sensitive and resistant to polymyxin and tetracycline. All fatty acid extracts from antibiotic resistant Gramnegative organisms contained higher concentrations of cyclopropane acids than the corresponding extracts from sensitive organisms. Thus, cyclopropane acids and unsaturated fatty acids appear to play a role in the integrity of the penetration barrier at least for polymyxin and tetracycline. 

J( C-H), which is 161 Hz in the case of cyclopropane and 123 Hz in the case of cyclohexane, supports the thesis that the dominant factor in cyclopropane acidity is the amount of s character in the exocyclic C-H bonds. 

While the Sharpless asymmetric dihydroxylation procedure proved effective in making the desired chiral cyclopropane acid intermediate from 5, several unit operations were required to make the key intermediate 2 b. Overall efficiency, however, is the key criterion for developing a long-term, cost-effective manufacturing process. Asymmetric cyclopropanation [18] certainly offered the most direct approach starting from 5, and so a number of catalyst systems known to effect this type of reaction were screened. Three catalytic systems were examined in detail for potential, as outlined in Tab. 1. 

Even thiophene itself will react with carbenes, at sulfur, to produce isolable thiophenium ylides, and in these, the sulfur is definitely tetrahedral. The rearrangement of thiophenium bis(ethoxycarbonyl) methylide to the 2-substituted thiophene provides a rationalisation for the reaction of thiophene with ethyl diazoacetate, which produces what appears to be the product of carbene addition to the 2,3-double bond perhaps this proceeds via initial attack at sulfur followed by S C-2 rearrangement, then collapse to the cyclopropane. Acid catalyses conversion of the cyclopropanated compound into a thiophene-3-acetic ester. ° 2,5-Dichlorothiophenium bis(methoxycarbonyl)methylide has been used as an efficient source of the carbene simply heating it in an alkene results in the transfer of (Me02C)2C to the alkene. ... 

Cyclopropane fatty acids occur frequently in bacterial membrane phospholipids. Also, they generally accompany the cyclopropene acids in seed oils (see following paragraph). Though other chain lengths have been reported, the most common cyclopropane acids are Cu and C19 (lactobacillic acid) compounds. They are probably formed from appropriate olefinic acids (16 1 9c and 18 111c) which are widely distributed in bacterial lipids. The cyclopropane acids have cis configuration but it is not clear whether they are individual enantiomers or racemic mixtures. 

The analysis of cyclopropane acids was reviewed by Minnikin (1978) and by Christie (1970), who also covered cyclopropene acids. Subsequently, Sebedio and Grandgirard (1989) discussed naturally occuring cyclic acids and cyclic acids formed in heated vegetable oils. Cyclic acids were the subject of a recent review (Le Quere and Sebedio, 1996). Useful information on gas chromatography (GC), mass spectrometry (MS) and high-pressure liquid chromatography (HPLC) of cyclic fatty acids can be found in books by Christie (1987, 1989). In the present chapter the aim is to concentrate on the more recent literature and those publications considered to be particularly... 

Figure 5.1 Structures of naturally occurring cyclic fatty acids. I, Cyclopropane acids a, 9,10-methylenehexadecanoic acid b, 11,12-methyleneoctadecanoic (lactobacillic) acid c, 8,9-methy-leneheptadecanoic (dihydromalvalic) acid d, 9,10-methyleneoctadecanoic (dihydrosterculic) acid. II, Mycolic (2-alkyl-3-hydroxy) acid. Ill, Cyclopropene acids a, 9,10-methyleneoctadec-9-enoic (sterculic) acid b, 8,9-methyleneheptadec-8-enoic (malvalic) acid. IV, Cyclopentenyl acids a, ll-cyclopent-2-enyl-undecanoic (hydnocarpic) acid b, 13-cyclopent-2-enyl-tridecanoic (chaulmoogric) acid c, 13-cyclopent-2-enyl-tridec-6-enoic (gorlic) acid. V a, 11-cyclohexyl-undecanoic acid b, 11-cycloheptylundecanoic acid.

The two common cyclopropane acids present in bacteria are 9,10-methylene-hexadecanoic acid (structure la. Fig. 5.1) and 11,12-methyleneoctadecanoic... 

Traditional procedures for quantification of total cyclopropene acid content have been reviewed by Christie (1970) and include titration with hydro-bromic acid and GC of the methyl mercaptan derivatives, products from reaction with silver nitrate/methanol and from methanethiol addition. However, a colorimetric test involving reaction with sulphur/carbon disulphide (the Halphen test) was found to be one of the most reliable methods for determining the small levels of cyclopropene acids present in oils containing cottonseed oil (Coleman, 1970). Another approach is GC of the relatively stable cyclopropane acids after hydrogenation with hydrazine (Conway, Ratnayake and Ackman, 1985)... 

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