78037-99-7Relevant academic research and scientific papers
Identification and absolute configuration of dihydroxy-arachidonic acids formed by oxygenation of 5 S-HETE by native and aspirin-acetylated COX-2
Mulugeta, Surafel,Suzuki, Takashi,Hernandez, Noemi Tejera,Griesser, Markus,Boeglin, William E.,Schneider, Claus
experimental part, p. 575 - 585 (2010/09/04)
Biosynthesis of the prostaglandin endoperoxide by the cyclooxygenase (COX) enzymes is accompanied by formation of a small amount of 11 R- hydroxyeicosatetraenoic acid (HETE), 15 R-HETE, and 15 S-HETE as by-products. Acetylation of COX-2 by aspirin abrogates prostaglandin synthesis and triggers formation of 15 R-HETE as the sole product of oxygenation of arachidonic acid. Here, we investigated the formation of by-products of the transformation of 5 S-HETE by native COX-2 and by aspirin-acetylated COX-2 using HPLC-ultraviolet, GC-MS, and LC-MS analysis. 5 S,15 S-dihydroxy (di)HETE, 5 S,15 R-diHETE, and 5 S,11 R-diHETE were identified as by-products of native COX-2, in addition to the previously described di-endoperoxide (5 S,15 S-dihydroxy-9 S,11 R,8 S,12 S-diperoxy-6 E,13 E-eicosadienoic acid) as the major oxygenation product. 5 S,15 R-diHETE was the only product formed by aspirinacetylated COX-2. Both 5,15-diHETE and 5,11-diHETE were detected in CT26 mouse colon carcinoma cells as well as in lipopolysaccharide-activated RAW264.7 cells incubated with 5 S-HETE, and their formation was attenuated in the presence of the COX-2 specific inhibitor, NS-398. Aspirintreated CT26 cells gave 5,15-diHETE as the most prominent product formed from 5 S-HETE. 5 S,15 S-diHETE has been described as a product of the cross-over of 5-lipoxygenase (5-LOX) and 15-LOX activities in elicited rat mononuclear cells and human leukocytes, and our studies implicate crossover of the 5-LOX and COX-2 pathways as an additional biosynthetic route. Copyright
Reductive deprotection of silyl groups with Wilkinson's catalyst/catechol borane
Patel, Pranav,Chang, Chih-Tsung,Kang, Namin,Lee, Gue-Jae,Powell, William S.,Rokach, Joshua
, p. 5289 - 5292 (2008/02/09)
Traditionally silyl groups are deprotected with acids and fluorides. These methods are, however, less discriminating when multi-silyl groups are present in the same molecule, resulting in lower yields of the desired products. The manipulation of these functions during the total synthesis of natural products, for example, prostaglandins and isoprostanes, requires the selective protection and deprotection of these groups. We are reporting here on a mild, selective and efficient method for the reductive deprotection of silyl groups using Wilkinson's catalyst/catechol borane or catechol borane alone.
An efficient total synthesis of 5-(S)-HETE
Gueugnot, Sylvie,Alami, Mouad,Linstrumelle, Gerard,Mambu, Lengo,Petit, Yves,Larcheveque, Marc
, p. 6635 - 6646 (2007/10/03)
A short and convergent synthesis of (5S)-HETE 1a was accomplished by coupling of two easily accessible synthons 2 and 3a.
A chemoenzymatic approach to hydroperoxyeicosatetraenoic acids. Total synthesis of 5(S)-HPETE
Dussault,Lee
, p. 218 - 226 (2007/10/02)
A new synthetic approach to enantiomerically pure hydroperoxyeicosatetraenoic acids (HPETEs) is described in which the tetraene skeleton is assembled through chemoselective olefination of a protected hydroperoxy aldehyde. Soybean lipoxygenase-mediated dioxygenation of both natural and unnatural fats produces hydroperoxy dienes in high enantiomeric excess; the observed regioselectivity supports a revised hypothesis for substrate specificity. Protection of the diene hydroperoxides as peroxy ketals is followed by regioselective ozonolysis to afford enantiomerically pure 4-peroxy 2,3-enals which undergo olefination to produce peroxytetraenoates. Removal of the monoperoxy ketal and the methyl ester affords enantiomerically pure HPETEs. The generality of the strategy is illustrated with the first chemical synthesis of 5(S)-HPETE.
Stereochemistry and Mechanism of the Biosynthesis of Leukotriene A4 from 5(S)-Hydroperoxy-6(E),8,11,14(Z)-eicosatetraenoic Acid. Evidence for an Organoiron Intermediate
Corey, E. J.,Wright, Stephen W.,Matsuda, Seiichi P. T.
, p. 1452 - 1455 (2007/10/02)
The pathway of biosynthesis of leukotriene A4 (LTA4, 2) from 5(S)-hydroperoxy-6(E),8,11,14(Z)-eicosatetraenoic acid (5-S-HPETE, 1) has been explored by the comparative study of (S)- and (R)-lipoxygenase (LO) enzymes as catalysts.The purified LO from potato, an S-lipoxygenase, converts (anaerobically) 1 to 2 (determined as the characteristic hydrolysis mixture of two epimeric 5,6-diols and two epimeric 5,12-diols), as previously reported by Samuelsson et al.However, the 8-R-LO from the coral Plexaura homomalla transforms 1 (anaerobically) into 6-epi-LTA4 (6).Theobserved divergence of stereopathways agrees with predictions based on the intermediacy of organoiron intermediates in enzymic lipoxygenation (Scheme I) and detailed in Schemes II and III.Further evidence for the intervention of such intermediates has been obtained by trapping experiments under pure O2 at pressures of 1-60 atm.Under O2 pressure 1 is converted by the potato LO to a new product, the bis(hydroperoxide) 7, whereas the coral LO converts 1 to the diastereomeric bis(hydroperoxide) 9.
A General Strategy for the Synthesis of Monohydroxyeicosatetraenoic Acids: Total Synthesis of 5(S)-Hydroxy-6(E),8,11,14(Z)-eicosatetraenoic Acid (5-HETE) and 12(S)-Hydroxy-5,8,14(Z),10(E)-eicosatetraenoic Acid (12-HETE)
Nicolaou, K. C.,Ladduwahetty, T.,Taffer, I. M.,Zipkin, R. E.
, p. 344 - 347 (2007/10/02)
Stereocontrolled total syntheses of 5(S)-hydroxy-6(E),8,11,14(Z)-eicosatetraenoic acid (5-HETE) and 12(S)-hydroxy-5,8,14(Z),10(E)-eicosatetraenoic acid (12-HETE) via palladium(0)-copper(I) coupling technology are described.
A PRACTICAL PROCESS FOR LARGE-SCALE SYNTHESIS OF (S)-5-HYDROXY-6-TRANS-8,11,14-CIS-EICOSATETRAENOIC ACID (5-HETE)
Corey, E. J.,Hashimoto, Shun-ichi
, p. 299 - 302 (2007/10/02)
(S)-5-hydroxy-6-trans-8,11,14-cis-eicosatetraenoic acid (5-HETE) (1) and its enantiomer are readily available by a chemical synthesis from arachidonic acid which includes a chromatographic separation of diastereomeric urethanes (3) made from (+/-)-5-HETE methyl ester and the isocyanate 4 derived from dehydroabietylamine.
