676236-01-4

Upstream product

• 1104389-39-0 C₂₀H₂₈O₃ 
• 694-98-4 norborn-5-en-2-one 
• 20657-21-0 3-acetoxycyclopent-1-ene 
• 930-30-3 cyclopent-2-enone 
• 121-46-0 bicyclo[2.2.1]hepta-2,5-diene 
• 84559-56-8 (S)-methyl 2-(4-oxocyclopent-2-en-1-yl)acetate 
• 144868-47-3 1-{[(5-iodopentyl)oxy]methyl}-4-methoxybenzene 
• 67920-82-5 (S)-methyl 2-(cyclopent-2-en-1-yl)acetate 
• 3859-41-4 1,3-cyclopentadione 
• 197219-26-4 7-(4-methoxybenzyloxy)-2-heptyn-1-ol 
• 307497-64-9 (2Z)-6-(4'-methoxybenzyloxy)-2-hexen-1-ol 
• 3212-60-0 cyclopent-2-enol 

Downstream Products

• 102839-03-2 Δ12-prostaglandin J₂ 
• 87893-55-8 15d-PGJ₂ 
• 869801-12-7 (S,E)-4-((Z)-7-((4-methoxybenzyl)oxy)hept-2-en-1-yl)-5-((E)-oct-2-en-1-ylidene)cyclopent-2-enone 
• 676236-03-6 dienone compound 
• 596104-94-8 (Z)-7-((R,E)-2-((E)-oct-2-en-1-ylidene)-3-oxocyclopentyl)hept-5-enoic acid 

Relevant academic research and scientific papers

Total Synthesis of Δ12-Prostaglandin J3: Evolution of Synthetic Strategies to a Streamlined Process

The total synthesis of Δ12-prostaglandin J3(Δ12-PGJ3, 1), a reported leukemia stem cell ablator, through a number of strategies and tactics is described. The signature cross-conjugated dienone structural motif of 1 was forged by an aldol reaction/dehydration sequence from key building blocks enone 13 and aldehyde 14, whose lone stereocenters were generated by an asymmetric Tsuji–Trost reaction and an asymmetric Mukaiyama aldol reaction, respectively. During this program, a substituent-governed regioselectivity pattern for the Rh-catalyzed C?H functionalization of cyclopentenes and related olefins was discovered. The evolution of the synthesis of 1 from the original strategy to the final streamlined process proceeded through improvements in the construction of both fragments 13 and 14, exploration of the chemistry of the hitherto underutilized chiral lactone synthon 57, and a diastereoselective alkylation of a cyclopentenone intermediate. The described chemistry sets the stage for large-scale production of Δ12-PGJ3and designed analogues for further biological and pharmacological studies.

Total Synthesis of Prostaglandin 15d-PGJ2 and Investigation of its Effect on the Secretion of IL-6 and IL-12

An efficient synthesis of 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2, 1) is reported. The route described allows for diversification of the parent structure to prepare seven analogues of 1 in which the positioning of electrophilic sites is varied. These analogues were tested in SAR studies for their ability to reduce the secretion of proinflammatory cytokines. It was shown that the endocyclic enone is crucial for the bioactivity investigated and that the conjugated ω-side chain serves in a reinforcing manner.

SYNTHESIS OF DELTA 12-PGJ3 AND RELATED COMPOUNDS

In one aspect, the present invention provides novel derivatives of Δ12-PGJ3 and modular synthetic pathways to obtaining Δ12-PGJ3 and derivatives thereof. In some aspects, the present derivatives of Δ12-PGJ3 are useful as chemotherapeutic agents. The present disclosure also describes compositions of these derivatives as well as methods of use of the derivatives thereof.

Synthesis of 14,15-epoxyisoprostane A2 phosphorylcholine

The product of the copper-promoted allylic substitution of the 4-hydroxycyclopent-2-enyl ester with TMS-C{triple bond, long}CCH2MgBr was converted to the cyclopentenone with the PMBO(CH2)4CH{double bond, long}CHCH2 side ch

Highly efficient total synthesis of Δ12-PGJ2, 15-deoxy-Δ12,14-PGJ2, and their analogues

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

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

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.