676236-01-4Relevant articles and documents
Total Synthesis of Δ12-Prostaglandin J3: Evolution of Synthetic Strategies to a Streamlined Process
Nicolaou,Pulukuri, Kiran Kumar,Yu, Ruocheng,Rigol, Stephan,Heretsch, Philipp,Grove, Charles I.,Hale, Christopher R. H.,ElMarrouni, Abdelatif
, p. 8559 - 8570 (2016/07/11)
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.
SYNTHESIS OF DELTA 12-PGJ3 AND RELATED COMPOUNDS
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Page/Page column 97, (2015/04/15)
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.
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.
