Reoptimization of the Organocatalyzed Double Aldol Domino Process to a Key Enal Intermediate and Its Application to the Total Synthesis of Δ12-Prostaglandin J3

Andrejs Pelšs; Narasimhulu Gandhamsetty; James R. Smith; Damien Mailhol; Mattia Silvi; Andrew J.A. Watson; Isabel Perez-Powell; Sébastien Prévost; Nina Schützenmeister; Peter R. Moore; Varinder K. Aggarwal

doi:10.1002/chem.201802498

Reoptimization of the Organocatalyzed Double Aldol Domino Process to a Key Enal Intermediate and Its Application to the Total Synthesis of Δ¹²-Prostaglandin J₃

Andrejs Pelšs
, Narasimhulu Gandhamsetty
, James R. Smith
, Damien Mailhol
, Mattia Silvi
, Andrew J.A. Watson
, Isabel Perez-Powell
, Sébastien Prévost
, Nina Schützenmeister
, Peter R. Moore
, Varinder K. Aggarwal^*

^*Corresponding author for this work

School of Chemistry

Research output: Contribution to journal › Article (Academic Journal) › peer-review

38 Citations (Scopus)

340 Downloads (Pure)

Abstract

Re-investigation of the l-proline catalyzed double aldol cascade dimerization of succinaldehyde for the synthesis of a key bicyclic enal intermediate, pertinent in the field of stereoselective prostaglandin synthesis, is reported. The yield of this process has been more than doubled, from 14 % to a 29 % isolated yield on a multi-gram scale (32 % NMR yield), through conducting a detailed study of the reaction solvent, temperature, and concentration, as well as a catalyst screen. The synthetic utility of this enal intermediate has been further demonstrated through the total synthesis of Δ¹²-prostaglandin J₃, a compound with known anti-leukemic properties.

Original language	English
Pages (from-to)	9542-9545
Number of pages	4
Journal	Chemistry - A European Journal
Volume	24
Issue number	38
Early online date	6 Jun 2018
DOIs	https://doi.org/10.1002/chem.201802498
Publication status	Published - 5 Jul 2018

Research Groups and Themes

BCS and TECS CDTs
Organic & Biological

Keywords

aldol reaction
organocatalysis
prostaglandins
total synthesis
Δ-PGJ

Access to Document

10.1002/chem.201802498

Full-text PDF (final published version)
This is the final published version of the article (version of record). It first appeared online via Wiley at https://onlinelibrary.wiley.com/doi/abs/10.1002/chem.201802498 . Please refer to any applicable terms of use of the publisher.
Final published version, 695 KBLicence: CC BY

Handle.net

Persistent link

Cite this

Pelšs, A., Gandhamsetty, N., Smith, J. R., Mailhol, D., Silvi, M., Watson, A. J. A., Perez-Powell, I., Prévost, S., Schützenmeister, N., Moore, P. R., & Aggarwal, V. K. (2018). Reoptimization of the Organocatalyzed Double Aldol Domino Process to a Key Enal Intermediate and Its Application to the Total Synthesis of Δ¹²-Prostaglandin J₃. Chemistry - A European Journal, 24(38), 9542-9545. https://doi.org/10.1002/chem.201802498

@article{31dd158508d14dfa8b44fea00e33e4ea,

title = "Reoptimization of the Organocatalyzed Double Aldol Domino Process to a Key Enal Intermediate and Its Application to the Total Synthesis of Δ12-Prostaglandin J3",

abstract = "Re-investigation of the l-proline catalyzed double aldol cascade dimerization of succinaldehyde for the synthesis of a key bicyclic enal intermediate, pertinent in the field of stereoselective prostaglandin synthesis, is reported. The yield of this process has been more than doubled, from 14 \% to a 29 \% isolated yield on a multi-gram scale (32 \% NMR yield), through conducting a detailed study of the reaction solvent, temperature, and concentration, as well as a catalyst screen. The synthetic utility of this enal intermediate has been further demonstrated through the total synthesis of Δ12-prostaglandin J3, a compound with known anti-leukemic properties.",

keywords = "aldol reaction, organocatalysis, prostaglandins, total synthesis, Δ-PGJ",

author = "Andrejs Pel{\v s}s and Narasimhulu Gandhamsetty and Smith, \{James R.\} and Damien Mailhol and Mattia Silvi and Watson, \{Andrew J.A.\} and Isabel Perez-Powell and S{\'e}bastien Pr{\'e}vost and Nina Sch{\"u}tzenmeister and Moore, \{Peter R.\} and Aggarwal, \{Varinder K.\}",

year = "2018",

month = jul,

day = "5",

doi = "10.1002/chem.201802498",

language = "English",

volume = "24",

pages = "9542--9545",

journal = "Chemistry - A European Journal",

issn = "0947-6539",

publisher = "John Wiley and Sons Inc",

number = "38",

}

Pelšs, A, Gandhamsetty, N, Smith, JR, Mailhol, D, Silvi, M, Watson, AJA, Perez-Powell, I, Prévost, S, Schützenmeister, N, Moore, PR & Aggarwal, VK 2018, 'Reoptimization of the Organocatalyzed Double Aldol Domino Process to a Key Enal Intermediate and Its Application to the Total Synthesis of Δ¹²-Prostaglandin J₃', Chemistry - A European Journal, vol. 24, no. 38, pp. 9542-9545. https://doi.org/10.1002/chem.201802498

Reoptimization of the Organocatalyzed Double Aldol Domino Process to a Key Enal Intermediate and Its Application to the Total Synthesis of Δ¹²-Prostaglandin J₃. / Pelšs, Andrejs; Gandhamsetty, Narasimhulu; Smith, James R. et al.
In: Chemistry - A European Journal, Vol. 24, No. 38, 05.07.2018, p. 9542-9545.

Research output: Contribution to journal › Article (Academic Journal) › peer-review

TY - JOUR

T1 - Reoptimization of the Organocatalyzed Double Aldol Domino Process to a Key Enal Intermediate and Its Application to the Total Synthesis of Δ12-Prostaglandin J3

AU - Pelšs, Andrejs

AU - Gandhamsetty, Narasimhulu

AU - Smith, James R.

AU - Mailhol, Damien

AU - Silvi, Mattia

AU - Watson, Andrew J.A.

AU - Perez-Powell, Isabel

AU - Prévost, Sébastien

AU - Schützenmeister, Nina

AU - Moore, Peter R.

AU - Aggarwal, Varinder K.

PY - 2018/7/5

Y1 - 2018/7/5

N2 - Re-investigation of the l-proline catalyzed double aldol cascade dimerization of succinaldehyde for the synthesis of a key bicyclic enal intermediate, pertinent in the field of stereoselective prostaglandin synthesis, is reported. The yield of this process has been more than doubled, from 14 % to a 29 % isolated yield on a multi-gram scale (32 % NMR yield), through conducting a detailed study of the reaction solvent, temperature, and concentration, as well as a catalyst screen. The synthetic utility of this enal intermediate has been further demonstrated through the total synthesis of Δ12-prostaglandin J3, a compound with known anti-leukemic properties.

AB - Re-investigation of the l-proline catalyzed double aldol cascade dimerization of succinaldehyde for the synthesis of a key bicyclic enal intermediate, pertinent in the field of stereoselective prostaglandin synthesis, is reported. The yield of this process has been more than doubled, from 14 % to a 29 % isolated yield on a multi-gram scale (32 % NMR yield), through conducting a detailed study of the reaction solvent, temperature, and concentration, as well as a catalyst screen. The synthetic utility of this enal intermediate has been further demonstrated through the total synthesis of Δ12-prostaglandin J3, a compound with known anti-leukemic properties.

KW - aldol reaction

KW - organocatalysis

KW - prostaglandins

KW - total synthesis

KW - Δ-PGJ

UR - https://www.scopus.com/pages/publications/85049605306

U2 - 10.1002/chem.201802498

DO - 10.1002/chem.201802498

M3 - Article (Academic Journal)

C2 - 29774967

AN - SCOPUS:85049605306

SN - 0947-6539

VL - 24

SP - 9542

EP - 9545

JO - Chemistry - A European Journal

JF - Chemistry - A European Journal

IS - 38

ER -

Reoptimization of the Organocatalyzed Double Aldol Domino Process to a Key Enal Intermediate and Its Application to the Total Synthesis of Δ¹²-Prostaglandin J₃

Abstract

Research Groups and Themes

Keywords

Access to Document

Handle.net

Other files and links

Fingerprint

Synthesis and Biology of Prostanoids

Cite this

Reoptimization of the Organocatalyzed Double Aldol Domino Process to a Key Enal Intermediate and Its Application to the Total Synthesis of Δ12-Prostaglandin J3

Abstract

Research Groups and Themes

Keywords

Access to Document

Handle.net

Other files and links

Fingerprint

Projects

Synthesis and Biology of Prostanoids

Cite this

Reoptimization of the Organocatalyzed Double Aldol Domino Process to a Key Enal Intermediate and Its Application to the Total Synthesis of Δ¹²-Prostaglandin J₃