Synthesis of leukotrienes labelled with deuterium: [11,12,14,15‐²H₄]‐LTA₄ ‐LTC₄, ‐LTD₄ and ‐LTE₄

Abstract

Semi-hydrogenation by 02 gas on L i n d l a r c a t a l y s t o f an a c e t y l e n i c precursor l e d t o [ l l , 12,14,15-2H4]-LTA4 methyl e s t e r -Ia. N u c l e o p h i l i c opening o f t h e epoxide r i n g by amino t h i o a c i d s afforded a f t e r saponificat i o n t h e corresponding deuterated peptidoleukotrienes LTC4, LTD4 and LTE4. -

Are Alkyne Reductions Chemo-, Regio-, and Stereoselective Enough To Provide Pure (Z)-Olefins in Polyfunctionalized Bioactive Molecules?

“…Likewise, starting from a skipped triyne, d 6 -linolenic acid was synthezised to investigate the biosynthesis of δ-jasmin lactone in the yeast Sporobolomyces odorus using GC-MS method. 359 A d 6 -deuterated tetraenoic C19 fatty acid was prepared (>95% Scheme 40 Scheme 41 338 Scheme 42 378 Chemical Reviews H 6 , 65% yield) for investigation on the biosynthesis of pheromones in female gametes of marine brown algae. 342 Application of this process to tetrayne precursors led to the successful synthesis of 3-hydroxyoxylipins with tritium on all the double bonds, i.e [ 3 H 8 ]-3(R)-HETE (64% after saponification) and [ 3 H 8 ]-3(R),18(R/S)-DiHETE (56%): the final tritiated products were obtained with specific activities ranging from 1.65 to 1.80 Ci/mmol.…”

“…Some authors replaced quinoline with triethylamine ,, or pyridine (with different ranges of amount = 1/10,000, 1% pyridine). Lellouche et al , observed that the reaction mixture (hexane) must contain exactly 0.01% pyridine in volume. An excess of pyridine (0.02–0.05%) inhibits hydrogen or deuterium absorption.…”

“…Besides ( Z )- or ( E )-allylic functions, ,,, cyclic double bond, isolated ( E )- , or ( Z )- , double bond, conjugated ( E )-olefin, ,, or a terminal alkene, the semireduction of isolated alkynes and/or poly skipped diynes also showed a high chemoselectivity in the presence of ( Z , Z )-bis-allylic systems, , but it is also respectful of conjugated 1,3-diene (( E , Z )-diene ,, or ( E , E )-diene , ) and conjugated ( E , E , E )-triene . Thus, this methodology is widely used in the synthesis of natural products such as leukotriene B4, , HETEs, , lipoxins, − 11-hydroxy linoleic acid, and related eicosanoids, but also cyclic PUFA metabolites such as 15-E 2 -isoprostane or pheromones (identification in female gametes of Analipus japonicus) , carotenoids. , …”

“…Skipped diyne systems were used as precursors for the incorporation of four tritium or deuterium atoms in the synthesis of labeled 5-oxo-ETEs . Application to the preparation of chemically sensitive structures such as leukotriene d 4 -LTA4 was also reported (Scheme ). − Over-reduction and decomposition of the epoxydiene during the purification step dramatically lowered the yield of the semireduction step.…”