Leucotriene synthesis

The anti-inflammatory activity of curcumin and its derivatives is associated with the hydroxyl and phenol groups in the molecule, which are also essential for the inhibition of prostaglandins, PG synthetase and leucotriene synthesis (LT) (Kiuchi et al., 1982, 1992 Iwakami, et al, 1986). Claeson et al. (1993, 1996) suggested that the antiinflammatory action and the antiparasitic activity were associated with the (3-dicarbo-nylic system with conjugated double bonds (dienes) (Araujo et al., 1998, 1999). The better skin penetration and lipophylicity is attributed to the presence of a diene ketone system. Calebin-A, a novel curcuminoid isolated from turmeric, protects neuronal cells from (3-amyloid insult. The hydroxy group at para-position of this compound is most critical for the expression of biological activity (Kim et al., 2001). 

Numerous chiral auxiliaries are known today. For instance, acetals derived from tartaric acid enable the preparation of enantiomerically pure cyclopropanated aldehydes (22 —> 23 24 —> 25) (Scheme 5). Aldehyde 25 is a key intermediate in the synthesis of leucotriene inhibitor 26 [27]. 

Fig. 3.10 Synthesis of eico-sanoids (leucotriene B4, B5, prostaglandin I2, I3, and thromboxane A2, A3) from n-3 and n-6 fatty acids...

Homoconjugated or skipped trienes are vital components of natural products such as fatty acids, leucotrienes and insect pheromones. Pohnert and Boland have reported a detailed discussion of the synthesis of these molecules using a one-pot Wittig approach which employs bis(ylides) (77), (78) and (79) as key building blocks.New one-pot Wittig procedures have also been developed for the synthesis of alkynes and bromoalkynes (Scheme 13) and iodoalkynes (Scheme 14). The latter process utilises diiodomethyltriphenyl-phosphorane (80), which is generated in situ from triphenylphosphine, iodoform and potassium butoxide. 

Within the last ten years, a large number of papers have appeared in which the titanium/tartrate-catalyzed asymmetric epoxidation of allylic alcohols was used as a key step in the synthesis of carbohydrates, amino acids, pheromones, leucotrienes and other stereochemically homogeneous compounds. This development has been discussed in several reviews [20],... 

Leucotrienes are substances that are implicated in asthmatic conditions, and thus their synthesis, or at least the synthesis of their precursors, is of pharmaceutical interest. Two approaches to the synthesis of (56) have been published. The first involves the treatment of the f/ireo-hydroxy-ester lactone... 

Chiral sulfoxides can also be used in a stereodivergent manner to construct homoallylic alcohols, which are common structure motifs in the total synthesis of natural products - prominent examples are the leucotrienes. They can be synthesized readily from a-sulfinyl epoxides as described in Scheme 3.24 [46]. 

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