Details
| Original language | English |
|---|---|
| Pages (from-to) | 8559-8570 |
| Number of pages | 12 |
| Journal | Chemistry - A European Journal |
| Volume | 22 |
| Issue number | 25 |
| Publication status | Published - 13 Jun 2016 |
| Externally published | Yes |
Abstract
The total synthesis of Δ 12-prostaglandin J 3(Δ 12-PGJ 3, 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 Δ 12-PGJ 3and designed analogues for further biological and pharmacological studies.
Keywords
- antitumor agent, asymmetric catalysis, chiral auxiliary, prostaglandin, total synthesis
ASJC Scopus subject areas
- Chemical Engineering(all)
- Catalysis
- Chemistry(all)
- Organic Chemistry
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In: Chemistry - A European Journal, Vol. 22, No. 25, 13.06.2016, p. 8559-8570.
Research output: Contribution to journal › Article › Research › peer review
}
TY - JOUR
T1 - Total Synthesis of Δ 12-Prostaglandin J 3
T2 - Evolution of Synthetic Strategies to a Streamlined Process
AU - Nicolaou, K. C.
AU - Pulukuri, Kiran Kumar
AU - Yu, Ruocheng
AU - Rigol, Stephan
AU - Heretsch, Philipp
AU - Grove, Charles I.
AU - Hale, Christopher R. H.
AU - ElMarrouni, Abdelatif
N1 - Publisher Copyright: © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
PY - 2016/6/13
Y1 - 2016/6/13
N2 - The total synthesis of Δ 12-prostaglandin J 3(Δ 12-PGJ 3, 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 Δ 12-PGJ 3and designed analogues for further biological and pharmacological studies.
AB - The total synthesis of Δ 12-prostaglandin J 3(Δ 12-PGJ 3, 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 Δ 12-PGJ 3and designed analogues for further biological and pharmacological studies.
KW - antitumor agent
KW - asymmetric catalysis
KW - chiral auxiliary
KW - prostaglandin
KW - total synthesis
UR - http://www.scopus.com/inward/record.url?scp=84970003913&partnerID=8YFLogxK
U2 - 10.1002/chem.201601449
DO - 10.1002/chem.201601449
M3 - Article
VL - 22
SP - 8559
EP - 8570
JO - Chemistry - A European Journal
JF - Chemistry - A European Journal
SN - 0947-6539
IS - 25
ER -