14,15-LTC4, synthesis

Mayatepek E, Zelezny R, Hoffmann GF. Analysis of leukotrienes in cerebrospinal fluid of a reference population and patients with inborn errors of metabolism further evidence for a pathognomonic profile in LTC4-synthesis deficiency. Clin Chim Acta 2000 292 155-162. 

Soon after, the complete structure of SRS-A was finally determined by total synthesis. SRS-A turned out to be a mixture of 3 substances now known as leukotriene C4 (LTC4), leukotriene D4 (LTD4) and leukotriene E4 (LTE4) in which LTD4 was predominant. The jump from a biological observation in 1938 to a molecular structure of LTD4 opened the door to a novel and selective treatment for asthma. The theory was that if one... 

The predecessor of Ultraflne was the Fine Chemicals Unit of Salford University Industrial Centre, which was set up partly to exploit a new route to prostaglandins.9 When the independent company was founded, it made sense to offer other eicosanoids. A key intermediate for the synthesis of leukotriene A4 (LTA4) (7), and thence LTC4, LTD4, and LTE4, was the epoxyalcohol (10), whose synthesis from 2-deoxy-D-ribose (8) (Scheme 29.2) had been reported.10... 

D, Synthesis of LTC4, LTD4, LTE4, LTF4, and Their Epimers... 

The Samuelsson proposal for the chemical nature of SRS acted as a powerful catalyst and resulted in the mobilization of a large part of the research community, which led, in 1979/1980, to the synthesis (Corey et al. and the Merck Frosst group ) and characterization of the elusive SRS-A as a mixture of LTC4, LTD4, and LTE4 (Scheme 1.3). 

A third synthesis of racemic 5-HETE has been reported by Rokach and coworkers, as outlined in Scheme3.2. Its basis stems from several observations made during the course of their original synthesis of LTC4 discussed... 

LTD4 and found that these fully functionalized leukotrienes also readily undergo the same [l,7]-hydrogen migration to produce the conjugated tetraene isomers 44. The Lilly group also concluded that an earlier report of the synthesis of (9Z)-LTC4 was in error and that the (9Z, 1 l )-isomer had actually been obtained. 

This biomimetic route represents a convenient synthesis of small amounts of LTA4 and hence of LTC4, LTD4, and LTE4,but the reactivity of the peroxide intermediates would probably make scale-up difficult. 

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