122069-57-2Relevant articles and documents
Stereoselective synthesis of protectin D1: A potent anti-inflammatory and proresolving lipid mediator
Aursnes,Tungen,Vik,Dalli,Hansen
, p. 432 - 437 (2014)
A convergent stereoselective synthesis of the potent anti-inflammatory, proresolving and neuroprotective lipid mediator protectin D1 (2) has been achieved in 15% yield over eight steps. The key features were a stereocontrolled Evans-aldol reaction with Nagao's chiral auxiliary and a highly selective Lindlar reduction of internal alkyne 23, allowing the sensitive conjugated E,E,Z-triene to be introduced late in the preparation of 2. The UV and LC/MS-MS data of synthetic protectin D1 (2) matched those obtained from endogenously produced material.
Total synthesis of the potent anti-inflammatory lipid mediator Protectin D1
Rodriguez, Ana R.,Spur, Bernd W.
, p. 6011 - 6015 (2014)
The total synthesis of the potent anti-inflammatory lipid mediator Protectin D1 derived from docosahexaenoic acid, has been achieved. The chiral hydroxy-groups at C10 and C17 were obtained via a chiral pool strategy from (4R)-4-(2-hydroxyethyl)-2,2-dimethyl-1,3-dioxolane and 3,4-O-isopropylidene-2-deoxy-d-ribose, respectively. Wittig reactions, Takai olefination, Pd0/CuISonogashira coupling, and Zn(Cu/Ag) reduction completed the total synthesis of Protectin D1.
Total Synthesis of the Antidiabetic (Type 2) Lipid Mediator Protectin DX/PDX
Sancéau, Jean-Yves,Maltais, René,Poirier, Donald,Marette, André
, p. 495 - 505 (2019)
The first total synthesis of a lipid mediator derived from natural ?-3-fatty acid docosahexaenoic acid (DHA), 10S,17S-diHDHA (also referred to as protectin DX/PDX), was achieved in a convergent route (29 steps). The two chiral hydroxyl groups at C-10 and
A versatile and stereocontrolled total synthesis of dihydroxylated docosatrienes containing a conjugated E,E,Z-triene
Dayaker, Gandrath,Durand, Thierry,Balas, Laurence
, p. 2879 - 2887 (2014/03/21)
A versatile strategy featuring a Colvin rearrangement, hydrozirconation, a Sonogashira cross-coupling reaction and a Z-selective Wittig olefination, was successfully developed for the construction of a conjugated E,E,Z-triene subunit, flanked on both sides by two Z-allylic hydroxyl groups. This chemical pattern is found in many endogenous lipid metabolites such as maresin1 (MaR1), neuroprotectinD1 (NPD1), and its aspirin triggered-isomer AT-NPD1, which not only counter-regulate inflammation but also actively orchestrate (at nanomolar doses) the resolution and termination program of acute inflammation while promoting wound healing, return to homeostasis and neuroprotection. Unlike previous approaches, the advantages of the present strategy are obvious, as it allows us to modify the nonpolar tail, the carboxylated head or both ends of the molecule without repeating the whole synthetic sequence (about 26-34steps according to the literature). Thus, the first total syntheses of NPD1 methyl ester epimer (which can also be considered as an enantiomer of AT-NPD1) and its n-3 docosapentaenoic acid derived analogue were achieved from a highly functionalized and late advanced pivotal intermediate. This innovative route may be easily adapted to gain access to other dihydroxylated metabolites and analogues of polyunsaturated fatty acids containing a conjugated E,E,Z-triene subunit. Different epimers/diastereoisomers may be obtained by purchasing the suitable optically pure (S)- and/or (R)-1,2,4-butanetriol(s) as a chiral pool for both stereogenic centers. Modification is key: Two total syntheses of dihydroxylated and noncyclic metabolites of polyunsaturated fatty acids, that is, NPD1 methyl ester epimer and its n-3 docosapentaenoic acid (DPA)-derived analogue, were achieved from a highly functionalized and late advanced pivotal intermediate (see scheme).
