1,2-Addition 1.2- double

Mammals can add additional double bonds to unsaturated fatty acids in their diets. Their ability to make arachidonic acid from linoleic acid is one example (Figure 25.15). This fatty acid is the precursor for prostaglandins and other biologically active derivatives such as leukotrienes. Synthesis involves formation of a linoleoyl ester of CoA from dietary linoleic acid, followed by introduction of a double bond at the 6-position. The triply unsaturated product is then elongated (by malonyl-CoA with a decarboxylation step) to yield a 20-carbon fatty acid with double bonds at the 8-, 11-, and 14-positions. A second desaturation reaction at the 5-position followed by an acyl-CoA synthetase reaction (Chapter 24) liberates the product, a 20-carbon fatty acid with double bonds at the 5-, 8-, IT, and ITpositions. 

Introduction of an additional double bond into the tricyclic nucleus, on the other hand, is consistent with antidepressant activity. Alkylation of the potassium salt, obtained on treatment of hydrocarbon, 38, with ammonia, with the chlorocarbamate, 39, affords the intermediate, 40. Basic hydrolysis leads to protrip-tylene (41). ... 

Dotz reaction, since both an alkyne and CO are inserted. However, the additional double bond present in the starting complex participates in the subsequent electrocyclic ring closure, giving rise to eight-membered carbocycles. 

Additional double bonds introduced into existing mo-nounsamrated fatty acids are always separated from each other by a methylene group (methylene interrupted) except in bacteria. Since animals have a desaturase, they... 

Heating of oxyprotoberberine 55, derived from dehydroprotoberberine (54), in methanol saturated with potassium hydroxide effected C-8—N bond cleavage to afford the zwitterionic salt 56, which was converted to amino ester 57 (Scheme 13) (50). The same reaction, however, could not be performed for oxyberberine (58), which lacks the additional double bond in ring B. 

On heating with sodium acetate and acetic anhydride under nitrogen, berberine (15) gave the naphthyl derivatives 61 and 62. The reaction proceeds as indicated in Scheme 15. Similar treatment of dehydroprotoberberine (54) gave the aromatized naphthylisoquinoline 63 owing to the presence of the additional double bond in ring B (52,53). 

Diterpenoids related to lambertianic acid were prepared by intramolecular cyclization of either an alkene or an alkyne with a furan ring <2005RJ01145>. On heating amine 101 with allyl bromide, the intermediate ammonium ion 102 was formed which then underwent [4+2] cycloadditions in situ to give the spiroazonium bromides 103 and 104 (Scheme 13). These isomers arose from either endo- or co-transition states. The analogous reaction was also carried out with the same amine 101 and propargyl bromide. The products 105 and 106 contain an additional double bond and were isolated in 58% yield. The product ratios of 103 104 and 105 106 were not presented. 

From Expt. 1 and Expt. 2 we see that [B] remains fixed while [A] triples. As a result, the initial rate increases from 4.2 x 10"3 M/min to 1.3 x 10 2 M/min, that is, the initial reaction rate triples. Therefore, the reaction is first-order in [A]. Between Expt. 2 and Expt. 3, we see that [A] doubles, which would double the rate, and [B] doubles. As a consequence, the initial rate goes from 1.3 x 10 2 M/min to 5.2 x 10 2 M/min, that is, the rate quadruples. Since an additional doubling of the rate is due to the change in [B], the reaction is first-order in [B]. Now we determine the value of the rate constant. 

Most of the kinetic models predict that the sulfite ion radical is easily oxidized by 02 and/or the oxidized form of the catalyst, but this species was rarely considered as a potential oxidant. In a recent pulse radiolysis study, the oxidation of Ni(II and I) and Cu(II and I) macrocyclic complexes by SO was studied under anaerobic conditions (117). In the reactions with Ni(I) and Cu(I) complexes intermediates could not be detected, and the electron transfer was interpreted in terms of a simple outer-sphere mechanism. In contrast, time resolved spectra confirmed the formation of intermediates with a ligand-radical nature in the reactions of the M(II) ions. The formation of a product with a sulfonated macrocycle and another with an additional double bond in the macrocycle were isolated in the reaction with [NiCR]2+. These results may require the refinement of the kinetic model proposed by Lepentsiotis for the [NiCR]2+ SO/ 02 system (116). 

The additional double loop analysis gives more detailed information regarding the 44 ineffective control elements, distinguishing true ineffective elements of the single loop from the false ineffective elements that in fact concern the double loop learning , i.e. an ineffective steering element. The results of this additional analysis are presented in Figure 37. 

The additional double bond in the corresponding allenyl 2-nitrophenyl sulphides causes a significant preference of the oxygen transfer to carbon88. The dominant ions correspond to the radical cations of 2[3//]-benzothiazolone and protonated benzothiazole, respectively88. Both ions require the transfer of two oxygens to carbon in the side-chain as well as extensive rearrangements of the molecules see Scheme 22. The transfer of... 

Note that arachidonic acid differs from EPA only in that the latter has one additional double bond near the methyl end of the molecule. Arachidonic acid is an omega-6 fatty acid. 

The DBF number is most useful when it comes to deciding which of perhaps two or three possible molecular formulae are correct. If there is a strong possibility that a particular unknown is related to the parent drug, for example, and that drug had a ring system with a DBF of 5, then the unknown should have a value of at least 5, and more if additional double bonds were introduced. 

---