The first synthesis of a borylated α-methylene-γ-butyrolactone

P. Veeraraghavan Ramachandran, Daniel R. Nicponski, Michael P. Drolet, C. Schmidt, Michele Yip-Schneider

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Background: The Michael acceptor scaffolding is a source of rich biological activity for α-methylene-γ-butyrolactones and their derivatives. A wide variety of these structures are present in many natural products that are well-known for their useful medicinal properties. Results: The first example of a borylated α-methylene-γ-butyrolactone is presented herein, along with its antipancreatic cancer activities against Panc-1, MIA PaCa-2 and BXPC-3. The synthetic route chosen allows for a wide range of lactones to be synthesized through different cross-coupling reactions starting from arylic bromide precursors. The precursors were synthesized by way of a highly efficient, chemoselective and indium-promoted Barbier reaction. Specifically, the indium metal reacted with only one of two present bromide functionalities: an allylic bromide in the presence of an arylic one. The bromide precursors were also tested for activity in the same bioassay as the borylated lactone and parthenolide. Conclusion: Notably, these brominated compounds demonstrate a significantly higher level of activity than parthenolide.

Original languageEnglish
Pages (from-to)633-639
Number of pages7
JournalFuture Medicinal Chemistry
Volume5
Issue number6
DOIs
StatePublished - Apr 2013

Fingerprint

Bromides
Indium
Lactones
Cross Reactions
Biological Products
Biological Assay
Metals
Neoplasms
parthenolide

ASJC Scopus subject areas

  • Drug Discovery
  • Pharmacology
  • Molecular Medicine

Cite this

The first synthesis of a borylated α-methylene-γ-butyrolactone. / Ramachandran, P. Veeraraghavan; Nicponski, Daniel R.; Drolet, Michael P.; Schmidt, C.; Yip-Schneider, Michele.

In: Future Medicinal Chemistry, Vol. 5, No. 6, 04.2013, p. 633-639.

Research output: Contribution to journalArticle

Ramachandran, P. Veeraraghavan ; Nicponski, Daniel R. ; Drolet, Michael P. ; Schmidt, C. ; Yip-Schneider, Michele. / The first synthesis of a borylated α-methylene-γ-butyrolactone. In: Future Medicinal Chemistry. 2013 ; Vol. 5, No. 6. pp. 633-639.
@article{c8e8fb74f86740ea93a47830b83b2561,
title = "The first synthesis of a borylated α-methylene-γ-butyrolactone",
abstract = "Background: The Michael acceptor scaffolding is a source of rich biological activity for α-methylene-γ-butyrolactones and their derivatives. A wide variety of these structures are present in many natural products that are well-known for their useful medicinal properties. Results: The first example of a borylated α-methylene-γ-butyrolactone is presented herein, along with its antipancreatic cancer activities against Panc-1, MIA PaCa-2 and BXPC-3. The synthetic route chosen allows for a wide range of lactones to be synthesized through different cross-coupling reactions starting from arylic bromide precursors. The precursors were synthesized by way of a highly efficient, chemoselective and indium-promoted Barbier reaction. Specifically, the indium metal reacted with only one of two present bromide functionalities: an allylic bromide in the presence of an arylic one. The bromide precursors were also tested for activity in the same bioassay as the borylated lactone and parthenolide. Conclusion: Notably, these brominated compounds demonstrate a significantly higher level of activity than parthenolide.",
author = "Ramachandran, {P. Veeraraghavan} and Nicponski, {Daniel R.} and Drolet, {Michael P.} and C. Schmidt and Michele Yip-Schneider",
year = "2013",
month = "4",
doi = "10.4155/fmc.13.37",
language = "English",
volume = "5",
pages = "633--639",
journal = "Future Medicinal Chemistry",
issn = "1756-8919",
publisher = "Future Science",
number = "6",

}

TY - JOUR

T1 - The first synthesis of a borylated α-methylene-γ-butyrolactone

AU - Ramachandran, P. Veeraraghavan

AU - Nicponski, Daniel R.

AU - Drolet, Michael P.

AU - Schmidt, C.

AU - Yip-Schneider, Michele

PY - 2013/4

Y1 - 2013/4

N2 - Background: The Michael acceptor scaffolding is a source of rich biological activity for α-methylene-γ-butyrolactones and their derivatives. A wide variety of these structures are present in many natural products that are well-known for their useful medicinal properties. Results: The first example of a borylated α-methylene-γ-butyrolactone is presented herein, along with its antipancreatic cancer activities against Panc-1, MIA PaCa-2 and BXPC-3. The synthetic route chosen allows for a wide range of lactones to be synthesized through different cross-coupling reactions starting from arylic bromide precursors. The precursors were synthesized by way of a highly efficient, chemoselective and indium-promoted Barbier reaction. Specifically, the indium metal reacted with only one of two present bromide functionalities: an allylic bromide in the presence of an arylic one. The bromide precursors were also tested for activity in the same bioassay as the borylated lactone and parthenolide. Conclusion: Notably, these brominated compounds demonstrate a significantly higher level of activity than parthenolide.

AB - Background: The Michael acceptor scaffolding is a source of rich biological activity for α-methylene-γ-butyrolactones and their derivatives. A wide variety of these structures are present in many natural products that are well-known for their useful medicinal properties. Results: The first example of a borylated α-methylene-γ-butyrolactone is presented herein, along with its antipancreatic cancer activities against Panc-1, MIA PaCa-2 and BXPC-3. The synthetic route chosen allows for a wide range of lactones to be synthesized through different cross-coupling reactions starting from arylic bromide precursors. The precursors were synthesized by way of a highly efficient, chemoselective and indium-promoted Barbier reaction. Specifically, the indium metal reacted with only one of two present bromide functionalities: an allylic bromide in the presence of an arylic one. The bromide precursors were also tested for activity in the same bioassay as the borylated lactone and parthenolide. Conclusion: Notably, these brominated compounds demonstrate a significantly higher level of activity than parthenolide.

UR - http://www.scopus.com/inward/record.url?scp=84876852726&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84876852726&partnerID=8YFLogxK

U2 - 10.4155/fmc.13.37

DO - 10.4155/fmc.13.37

M3 - Article

VL - 5

SP - 633

EP - 639

JO - Future Medicinal Chemistry

JF - Future Medicinal Chemistry

SN - 1756-8919

IS - 6

ER -