Olefin isomerization inhibitor

Terpene synthases, also known as terpene cyclases because most of their products are cyclic, utilize a carbocationic reaction mechanism very similar to that employed by the prenyltransferases. Numerous experiments with inhibitors, substrate analogues and chemical model systems (Croteau, 1987 Cane, 1990, 1998) have revealed that the reaction usually begins with the divalent metal ion-assisted cleavage of the diphosphate moiety (Fig. 5.6). The resulting allylic carbocation may then cyclize by addition of the resonance-stabilized cationic centre to one of the other carbon-carbon double bonds in the substrate. The cyclization is followed by a series of rearrangements that may include hydride shifts, alkyl shifts, deprotonation, reprotonation and additional cyclizations, all mediated through enzyme-bound carbocationic intermed iates. The reaction cascade terminates by deprotonation of the cation to an olefin or capture by a nucleophile, such as water. Since the native substrates of terpene synthases are all configured with trans (E) double bonds, they are unable to cyclize directly to many of the carbon skeletons found in nature. In such cases, the cyclization process is preceded by isomerization of the initial carbocation to an intermediate capable of cyclization. 

The Chemistry of Ring B.—The isolation of taxodione (49), a diterpenoid tumour inhibitor, has stimulated interest in the introduction of oxygen functions at C-6. Taxodione itself has been synthesized from podocarpic acid. The latter was converted to ferruginol benzoate (46). The C-11 hydroxy-group was introduced via the diazo-compound and the product acetoxylated at C-7 to afford (47) this was converted into the A -olefin (48), which was epoxidized and isomerized to the C-6 ketone. The product was then oxidized to give the quinone-methide of taxodione (49). 

Pentane isomerization was used to increase the critical supply of aviation gasoline toward the end of the war. Two processes—one developed by Shell and one by Standard Oil Company (Indiana)—were commercialized. The pentane processes differ from butane isomerization mainly in the use of somewhat milder conditions and an inhibitor to suppress side reactions. In general, the problems of the butane processes are inherent also in pentane isomerization, but the quality of the feed stock is less important. Olefins can be as high as 0.2 %, although 0.05 % is preferable. The hexane content should not exceed about 5%, and sulfur and water contents should be as low as in the butane process. Catalyst life is much shorter than in the butane processes only about 30-50 gallons of isopentane are produced per pound of aluminum chloride. 

The research team of J. Tadanier prepared a series of C8-modified 3-deoxy-P-D-manno-2-octulosonic acid analogues as potential inhibitors of CMP-Kdo synthetase. One of the derivatives was prepared from a functionalized olefinic carbohydrate substrate by means of the Wohl-Ziegler bromination. The stereochemistry of the double bond was (Z), however, under the reaction conditions a cis-trans isomerization took place in addition to the bromination at the allylic position (no yield was reported for this step). It is worth noting that the authors did not use a radical initiator for this transformation, the reaction mixture was simply irradiated with a 150W flood lamp. Subsequently the allylic bromide was converted to an allylic azide, which was then subjected to the Staudinger reaction to obtain the corresponding allylic amine. 

Vilar and coworkers [59] have investigated the use of additives to suppress olefin migration in the self-metathesis of urea derivatives (Scheme 12.33). The Af-allyl urea 109 was found to undergo self-metathesis in the presence of Ru catalyst 3 in 33% yield. The isomerized species 110 was isolated as the major product (55% yield, Z= 1 1). Vilar and coworkers identified phenylphosphoric acid (112) as an effective inhibitor of the undesired alkene isomerization. When the metathesis of Af-allyl urea 109 was performed with phenylphosphoric acid (50mol%), the desired dimer 111 was isolated in 56% yield, and 30% of the starting material 109 could be recovered. The authors also investigated the use of benzoquinone derivatives, and found that 2,6-dichloro-l,4-benzoquinone (10 mol%) was equally... 

The present modeling approach exploited these notions. The molecules in the paraffin hydrocracking reaction mixture were thus grouped into a few species types (paraffins, olefins, ions, and inhibitors such as NH3), which, in turn, reacted through a limited number of reaction families on the metal (dehydrogenation and hydrogenation) and the acid sites (protonation, hydride-shift, methyl-shift, protonated cyclopropane (PCP) isomerization, 13-scission, and deprotonation). As a result, a small munber of formal reaction operations could be used to generate hundreds of reactions. 

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