Palladium-catalyzed carbonylative transformations of bromhexine into bioactive compounds as glucocerebrosidase inhibitors

Muhammad Sharif; Anahit Pews-Davtyan; Jan Lukas; Johannes Schranck; Peter Langer; Arndt Rolfs; Matthias Beller

doi:10.1002/ejoc.201301180

Palladium-catalyzed carbonylative transformations of bromhexine into bioactive compounds as glucocerebrosidase inhibitors

Muhammad Sharif
, Anahit Pews-Davtyan
, Jan Lukas
, Johannes Schranck
, Peter Langer
, Arndt Rolfs^*
, Matthias Beller

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

10 Scopus citations

Abstract

A general synthesis for dicarbonylated derivatives of the parent drug bromhexine is described. By using the commercially available Pd(OAc) ₂/BuPAd₂ (CataCXium A, Ad = adamantyl) catalyst system, the carbonylative arylation, amination, and alkoxylation of bromhexine proceeded with up to 79 % product yield. Selected synthesized derivatives of bromhexine showed improved effects as glucocerebrosidase inhibitors. The first palladium-catalyzed carbonylative Suzuki-Miyaura arylations as well as alkoxy-and aminocarbonylations of the parent drug bromhexine were successfully performed. Some of the resulting new carbonylated products showed significant inhibition towards the glucocerebrosidase enzyme.

Original language	English
Pages (from-to)	222-230
Number of pages	9
Journal	European Journal of Organic Chemistry
Volume	2014
Issue number	1
DOIs	https://doi.org/10.1002/ejoc.201301180
State	Published - Jan 2014
Externally published	Yes

Keywords

Biological activity
Carbonylation
Cross-coupling
Inhibitors
Medicinal chemistry
Palladium

ASJC Scopus subject areas

Physical and Theoretical Chemistry
Organic Chemistry

Access to Document

10.1002/ejoc.201301180

Cite this

@article{44d16db744654577b6b7ed4f418b2960,

title = "Palladium-catalyzed carbonylative transformations of bromhexine into bioactive compounds as glucocerebrosidase inhibitors",

abstract = "A general synthesis for dicarbonylated derivatives of the parent drug bromhexine is described. By using the commercially available Pd(OAc) 2/BuPAd2 (CataCXium A, Ad = adamantyl) catalyst system, the carbonylative arylation, amination, and alkoxylation of bromhexine proceeded with up to 79 \% product yield. Selected synthesized derivatives of bromhexine showed improved effects as glucocerebrosidase inhibitors. The first palladium-catalyzed carbonylative Suzuki-Miyaura arylations as well as alkoxy-and aminocarbonylations of the parent drug bromhexine were successfully performed. Some of the resulting new carbonylated products showed significant inhibition towards the glucocerebrosidase enzyme.",

keywords = "Biological activity, Carbonylation, Cross-coupling, Inhibitors, Medicinal chemistry, Palladium",

author = "Muhammad Sharif and Anahit Pews-Davtyan and Jan Lukas and Johannes Schranck and Peter Langer and Arndt Rolfs and Matthias Beller",

year = "2014",

month = jan,

doi = "10.1002/ejoc.201301180",

language = "English",

volume = "2014",

pages = "222--230",

journal = "European Journal of Organic Chemistry",

issn = "1434-193X",

publisher = "Wiley-VCH Verlag",

number = "1",

}

TY - JOUR

T1 - Palladium-catalyzed carbonylative transformations of bromhexine into bioactive compounds as glucocerebrosidase inhibitors

AU - Sharif, Muhammad

AU - Pews-Davtyan, Anahit

AU - Lukas, Jan

AU - Schranck, Johannes

AU - Langer, Peter

AU - Rolfs, Arndt

AU - Beller, Matthias

PY - 2014/1

Y1 - 2014/1

N2 - A general synthesis for dicarbonylated derivatives of the parent drug bromhexine is described. By using the commercially available Pd(OAc) 2/BuPAd2 (CataCXium A, Ad = adamantyl) catalyst system, the carbonylative arylation, amination, and alkoxylation of bromhexine proceeded with up to 79 % product yield. Selected synthesized derivatives of bromhexine showed improved effects as glucocerebrosidase inhibitors. The first palladium-catalyzed carbonylative Suzuki-Miyaura arylations as well as alkoxy-and aminocarbonylations of the parent drug bromhexine were successfully performed. Some of the resulting new carbonylated products showed significant inhibition towards the glucocerebrosidase enzyme.

AB - A general synthesis for dicarbonylated derivatives of the parent drug bromhexine is described. By using the commercially available Pd(OAc) 2/BuPAd2 (CataCXium A, Ad = adamantyl) catalyst system, the carbonylative arylation, amination, and alkoxylation of bromhexine proceeded with up to 79 % product yield. Selected synthesized derivatives of bromhexine showed improved effects as glucocerebrosidase inhibitors. The first palladium-catalyzed carbonylative Suzuki-Miyaura arylations as well as alkoxy-and aminocarbonylations of the parent drug bromhexine were successfully performed. Some of the resulting new carbonylated products showed significant inhibition towards the glucocerebrosidase enzyme.

KW - Biological activity

KW - Carbonylation

KW - Cross-coupling

KW - Inhibitors

KW - Medicinal chemistry

KW - Palladium

UR - https://www.scopus.com/pages/publications/84890802119

U2 - 10.1002/ejoc.201301180

DO - 10.1002/ejoc.201301180

M3 - Article

AN - SCOPUS:84890802119

SN - 1434-193X

VL - 2014

SP - 222

EP - 230

JO - European Journal of Organic Chemistry

JF - European Journal of Organic Chemistry

IS - 1

ER -

Palladium-catalyzed carbonylative transformations of bromhexine into bioactive compounds as glucocerebrosidase inhibitors

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Fingerprint

Cite this