View in EDS

Catalytic synthesis of 9-cis-retinoids: mechanistic insights.

Saved in:
Bibliographic Details
Title: Catalytic synthesis of 9-cis-retinoids: mechanistic insights.
Authors: Kahremany, Shirin1,2, Kubas, Adam3, Tochtrop, Gregory P.4, Palczewski, Krzysztof1,2
Source: Dalton Transactions: An International Journal of Inorganic Chemistry. 7/28/2019, Vol. 48 Issue 28, p10581-10595. 15p.
Subjects: Drug synthesis, Heat treatment, Chemistry, Isomerization, Therapeutics, Isomers
Abstract: The regioselective Z-isomerization of thermodynamically stable all-trans retinoids remains challenging, and ultimately limits the availability of much needed therapeutics for the treatment of human diseases. We present here a novel, straightforward approach for the catalytic Z-isomerization of retinoids using conventional heat treatment or microwave irradiation. A screen of 20 transition metal-based catalysts identified an optimal approach for the regioselective production of Z-retinoids. The most effective catalytic system was comprised of a palladium complex with labile ligands. Several mechanistic studies, including isotopic H/D exchange and state-of-the-art quantum chemical calculations using coupled cluster methods indicate that the isomerization is initiated by catalyst dimerization followed by the formation of a cyclic, six-membered chloropalladate catalyst–substrate adduct, which eventually opens to produce the desired Z-isomer. The synthetic development described here, combined with thorough mechanistic analysis of the underlying chemistry, highlights the use of readily available transition metal-based catalysts in straightforward formats for gram-scale drug synthesis. [ABSTRACT FROM AUTHOR]
Copyright of Dalton Transactions: An International Journal of Inorganic Chemistry is the property of Royal Society of Chemistry and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Engineering Source
FullText Text:
  Availability: 0
Header DbId: egs
DbLabel: Engineering Source
An: 137686119
AccessLevel: 6
PubType: Academic Journal
PubTypeId: academicJournal
PreciseRelevancyScore: 0
IllustrationInfo
Items – Name: Title
  Label: Title
  Group: Ti
  Data: Catalytic synthesis of 9-cis-retinoids: mechanistic insights.
– Name: Author
  Label: Authors
  Group: Au
  Data: <searchLink fieldCode="AR" term="%22Kahremany%2C+Shirin%22">Kahremany, Shirin</searchLink><relatesTo>1,2</relatesTo><br /><searchLink fieldCode="AR" term="%22Kubas%2C+Adam%22">Kubas, Adam</searchLink><relatesTo>3</relatesTo><br /><searchLink fieldCode="AR" term="%22Tochtrop%2C+Gregory+P%2E%22">Tochtrop, Gregory P.</searchLink><relatesTo>4</relatesTo><br /><searchLink fieldCode="AR" term="%22Palczewski%2C+Krzysztof%22">Palczewski, Krzysztof</searchLink><relatesTo>1,2</relatesTo>
– Name: TitleSource
  Label: Source
  Group: Src
  Data: <searchLink fieldCode="JN" term="%22Dalton+Transactions%3A+An+International+Journal+of+Inorganic+Chemistry%22">Dalton Transactions: An International Journal of Inorganic Chemistry</searchLink>. 7/28/2019, Vol. 48 Issue 28, p10581-10595. 15p.
– Name: Subject
  Label: Subjects
  Group: Su
  Data: <searchLink fieldCode="DE" term="%22Drug+synthesis%22">Drug synthesis</searchLink><br /><searchLink fieldCode="DE" term="%22Heat+treatment%22">Heat treatment</searchLink><br /><searchLink fieldCode="DE" term="%22Chemistry%22">Chemistry</searchLink><br /><searchLink fieldCode="DE" term="%22Isomerization%22">Isomerization</searchLink><br /><searchLink fieldCode="DE" term="%22Therapeutics%22">Therapeutics</searchLink><br /><searchLink fieldCode="DE" term="%22Isomers%22">Isomers</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: The regioselective Z-isomerization of thermodynamically stable all-trans retinoids remains challenging, and ultimately limits the availability of much needed therapeutics for the treatment of human diseases. We present here a novel, straightforward approach for the catalytic Z-isomerization of retinoids using conventional heat treatment or microwave irradiation. A screen of 20 transition metal-based catalysts identified an optimal approach for the regioselective production of Z-retinoids. The most effective catalytic system was comprised of a palladium complex with labile ligands. Several mechanistic studies, including isotopic H/D exchange and state-of-the-art quantum chemical calculations using coupled cluster methods indicate that the isomerization is initiated by catalyst dimerization followed by the formation of a cyclic, six-membered chloropalladate catalyst–substrate adduct, which eventually opens to produce the desired Z-isomer. The synthetic development described here, combined with thorough mechanistic analysis of the underlying chemistry, highlights the use of readily available transition metal-based catalysts in straightforward formats for gram-scale drug synthesis. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
  Label:
  Group: Ab
  Data: <i>Copyright of Dalton Transactions: An International Journal of Inorganic Chemistry is the property of Royal Society of Chemistry and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
PLink https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=egs&AN=137686119
RecordInfo BibRecord:
  BibEntity:
    Identifiers:
      – Type: doi
        Value: 10.1039/c9dt02189b
    Languages:
      – Code: eng
        Text: English
    PhysicalDescription:
      Pagination:
        PageCount: 15
        StartPage: 10581
    Subjects:
      – SubjectFull: Drug synthesis
        Type: general
      – SubjectFull: Heat treatment
        Type: general
      – SubjectFull: Chemistry
        Type: general
      – SubjectFull: Isomerization
        Type: general
      – SubjectFull: Therapeutics
        Type: general
      – SubjectFull: Isomers
        Type: general
    Titles:
      – TitleFull: Catalytic synthesis of 9-cis-retinoids: mechanistic insights.
        Type: main
  BibRelationships:
    HasContributorRelationships:
      – PersonEntity:
          Name:
            NameFull: Kahremany, Shirin
      – PersonEntity:
          Name:
            NameFull: Kubas, Adam
      – PersonEntity:
          Name:
            NameFull: Tochtrop, Gregory P.
      – PersonEntity:
          Name:
            NameFull: Palczewski, Krzysztof
    IsPartOfRelationships:
      – BibEntity:
          Dates:
            – D: 28
              M: 07
              Text: 7/28/2019
              Type: published
              Y: 2019
          Identifiers:
            – Type: issn-print
              Value: 14779226
          Numbering:
            – Type: volume
              Value: 48
            – Type: issue
              Value: 28
          Titles:
            – TitleFull: Dalton Transactions: An International Journal of Inorganic Chemistry
              Type: main
ResultId 1