102839-03-2Relevant academic research and scientific papers
Concise Syntheses of ?"12-Prostaglandin J Natural Products via Stereoretentive Metathesis
Li, Jiaming,Ahmed, Tonia S.,Xu, Chen,Stoltz, Brian M.,Grubbs, Robert H.
, p. 154 - 158 (2019)
δ12-Prostaglandin J family is recently discovered and has potent anticancer activity. Concise syntheses of four δ12-prostaglandin J natural products (7-8 steps in the longest linear sequences) are reported, enabled by convergent stereoretentive cross-metathesis. Exceptional control of alkene geometry was achieved through stereoretention.
Short Total Synthesis of 12-Prostaglandin J2 and Related Prostaglandins. Design, Synthesis, and Biological Evaluation of Macrocyclic 12-Prostaglandin J2 Analogues
Nicolaou,Pulukuri, Kiran Kumar,Rigol, Stephan,Peitsinis, Zisis,Yu, Ruocheng,Kishigami, Satoshi,Cen, Nicholas,Aujay, Monette,Sandoval, Joseph,Zepeda, Nancy,Gavrilyuk, Julia
, p. 365 - 378 (2019/01/10)
Comprised of a large collection of structurally diverse molecules, the prostaglandins exhibit a wide range of biological properties. Among them are ?"12-prostaglandin J2 (?"12-PGJ2) and ?"12-prostagla
TOTAL SYNTHESIS OF PROSTAGLANDIN J NATURAL PRODUCTS BY STEREORETENTIVE METATHESIS
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, (2019/12/04)
This invention relates generally to the synthesis of Δ12-Prostaglandin J product using stereoretentive ruthenium olefin metathesis catalysts supported by dithiolate ligands. Δ12- Prostaglandin J products were generated with excellent selectivity (>99% Z) and in moderate to high/good yields (47% to 80% yield; 58% to 80% yield).
Δ12-Prostaglandin J2 as a product and ligand of human serum albumin: Formation of an unusual covalent adduct at His146
Yamaguchi, Satoru,Aldini, Giancarlo,Ito, Sohei,Morishita, Nozomi,Shibata, Takahiro,Vistoli, Giulio,Carini, Marina,Uchida, Koji
body text, p. 824 - 832 (2010/03/25)
Human serum albumin (HSA), the most abundant protein in plasma, has a very unique function, catalyzing the conversion of prostaglandin J2 (PGJ2), a dehydration product of PGD2, to yield Δ12-PGJ2. These PGD2 metabolites are actively transported into cells and accumulated in the nuclei, where they act as potent inducers of cell growth inhibition and cell differentiation, and exhibit their own unique spectrum of biological effects. The facts that (i) arachidonic acid metabolites bind to human serum albumin (HSA) and the metabolism of these molecules is altered as a result of binding, (ii) HSA catalyzes the transformation of PGJ2 into Δ12-PGJ2, and (iii) Δ12-PGJ2 is stable in serum suggest that HSA may bind and stabilize Δ12-PGJ2 in a specific manner. A molecular interaction analysis using surface plasmon resonance (Biacore) indeed suggested the presence of a specific Δ12-PGJ 2-binding site in HSA. To investigate the molecular details of the binding of this PGD2 metabolite to albumin, we analyzed the cocrystal structure of the HSA-Δ12-PGJ2-myristate complex by X-ray crystallography and found that two Δ12-PGJ12 molecules bind to a primary site in subdomain IB of the protein. The electron density results suggested that one of the two Δ12-PGJ 12 molecules that specifically bind to the site covalently interacted with a histidine residue (His146). Using nano-LC-MS/MS analysis of the HSA-Δ12-PGJ2 complex, the formation of an unusual Δ12-PGJ2-histidine adduct at His146 was confirmed. Thus, our crystallographic and mass spectrometric analyses of the HSA-Δ12-PGJ2 complex provided intriguing new insights into the molecular details of how this electrophilic ligand interacts with its primary producer and transporter.
Highly efficient total synthesis of Δ12-PGJ2, 15-deoxy-Δ12,14-PGJ2, and their analogues
Acharya, Hukum P.,Kobayashi, Yuichi
, p. 3329 - 3343 (2007/10/03)
Palladium-catalyzed reaction of TBS ether of 4-cyclopentene-1,3-diol monoacetate (>95% ee) with an anion derived from methyl malonate and a base such as t-BuOK and LDA proceeded highly efficiently and reproducibly. The product obtained in >90% isolated yield was transformed in five steps into the key cyclopentenone possessing the α-chain at the γ position. Aldol reaction of this enone with the ω-chain aldehyde afforded the aldol adduct, and exposure of the derived mesylate to Al2O3 furnished the cross-conjugated dienone of the full structure. Finally, functional group manipulation furnished Δ12-PGJ2 efficiently. Similarly, 15-deoxy-Δ12,14-PGJ2, 5,6-acetylene analogues, and a 5,6-dihydro analogue were synthesized.
METHOD FOR PRODUCING PROSTAGLANDIN DERIVATIVE, PROSTAGLANDIN DERIVATIVE, INTERMEDIATE COMPOUND THEREFOR AND METHOD FOR PRODUCING THE SAME
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Page/Page column 30, (2010/02/15)
PROBLEM TO BE SOLVED: To provide a method for producing a prostaglandin derivative, the prostaglandin derivative and an intermediate compound therefor, especially a method for producing a δ-12-prostaglandin J2 derivative using a new method for chemical synthesis through the intermediate compound. SOLUTION: The method for production is a method for producing the prostaglandin derivative using (1R,3R)-4-cyclopentene-1,3-diol 3-acetate (carboxylate) as a starting material. The method is composed of (A) an α-side chain introduction step of providing a malonic acid ester addition compound at the 3-position of the (1R,3R)-4-cyclopentene-1,3-diol, (B) an α-side chain extension step of affording a (1R,3R)-4-cyclopenten-1-one compound having the α-side chain of the prostaglandin derivative at the 3-position and (C) a prostaglandin derivative synthesizing step of conversion into the prostaglandin derivative.
Total synthesis of Δ12-PGJ2, 15-deoxy-Δ12,14-PGJ2, and related compounds
Acharya, Hukum P.,Kobayashi, Yuichi
, p. 1199 - 1202 (2007/10/03)
A key cyclopentenone possessing the α-chain was synthesized from TBS ether of 4-cyclopentene-1,3-diol monoacetate, and submitted to aldol reaction at the α′-position with the ω-chain aldehydes followed by dehydration to produce the title compounds. In a similar manner, 5-dehydro compounds (acetylene analogues) were synthesized successfully. In addition, palladium-catalyzed reaction of 4-cyclopentene-1,3-diol monoacetate with methyl malonate, the first step of the synthesis, was improved to afford the product in high yield by using t-BuOK or LDA in place of NaH.
