First total synthesis of pamamycin-621D

Hassan Norouzi-Arasi, Xavier J. Salom-Roig, Steve Lanners, Gilles Hanquet

Résultats de recherche: Contribution à un journal/une revueArticle

Résumé

Aim and Objective: The objective of our work was to synthesize and fully characterize Pamamycin-621D, one of the less abundant members of a large family of macrodiolides with antimycobacterial properties, which had never been synthesized before. Furthermore, we also wished to improve our general strategy by using a new unsaturated precursor. Material and Method: A new unsaturated ethylketone precursor was prepared using alkene cross metathesis, and a convergent and flexible strategy based on a key diastereoselective aldol addition was implemented to afford pamamycin-621D in 12 steps from that precursor. Results: Pamamycin-621D has been obtained and fully characterized for the first time. The structure of pamamycin-621D was confirmed by HRMS and comparison of1H-NMR spectra with the natural pamamycin-621D. Both optical rotation and13C-NMR had not been published previously due to lack of material, and the latter are reported here for the first time. Given the scarce characterization available previously, our synthesis also gives additional support to the initial structural assignment of pamamycin-621D. A significant improvement of the key aldol addition via the use of a new unsaturated precursor is also reported. Conclusion: The work described above constitutes the first total synthesis of pamamycin-621D and has enabled us to fully characterize this scarcely available natural product. More importantly, this work highlights the fact that our synthetic approach provides ready access to various members of the pamamycin family, allowing possible studies on structure-activity relationships and mode of action of even the least abundant of these natural products. The synthesis of other pamamycin congeners and biological investigations will be published in due course.

langue originaleAnglais
Pages (de - à)105-109
Nombre de pages5
journalCurrent Organic Synthesis
Volume15
Numéro de publication1
Les DOIs
étatPublié - 1 févr. 2018

Empreinte digitale

Biological Products
Nuclear magnetic resonance
Optical rotation
Optical Rotation
pamamycin
Alkenes
Structure-Activity Relationship
3-hydroxybutanal

Citer ceci

Norouzi-Arasi, Hassan ; Salom-Roig, Xavier J. ; Lanners, Steve ; Hanquet, Gilles. / First total synthesis of pamamycin-621D. Dans: Current Organic Synthesis. 2018 ; Vol 15, Numéro 1. p. 105-109.
@article{fdb306dcf1b24676a357502bf6cc399e,
title = "First total synthesis of pamamycin-621D",
abstract = "Aim and Objective: The objective of our work was to synthesize and fully characterize Pamamycin-621D, one of the less abundant members of a large family of macrodiolides with antimycobacterial properties, which had never been synthesized before. Furthermore, we also wished to improve our general strategy by using a new unsaturated precursor. Material and Method: A new unsaturated ethylketone precursor was prepared using alkene cross metathesis, and a convergent and flexible strategy based on a key diastereoselective aldol addition was implemented to afford pamamycin-621D in 12 steps from that precursor. Results: Pamamycin-621D has been obtained and fully characterized for the first time. The structure of pamamycin-621D was confirmed by HRMS and comparison of1H-NMR spectra with the natural pamamycin-621D. Both optical rotation and13C-NMR had not been published previously due to lack of material, and the latter are reported here for the first time. Given the scarce characterization available previously, our synthesis also gives additional support to the initial structural assignment of pamamycin-621D. A significant improvement of the key aldol addition via the use of a new unsaturated precursor is also reported. Conclusion: The work described above constitutes the first total synthesis of pamamycin-621D and has enabled us to fully characterize this scarcely available natural product. More importantly, this work highlights the fact that our synthetic approach provides ready access to various members of the pamamycin family, allowing possible studies on structure-activity relationships and mode of action of even the least abundant of these natural products. The synthesis of other pamamycin congeners and biological investigations will be published in due course.",
keywords = "Aldol reaction, Cross metathesis, Macrodiolides, Natural products, Pamamycin, Total synthesis",
author = "Hassan Norouzi-Arasi and Salom-Roig, {Xavier J.} and Steve Lanners and Gilles Hanquet",
year = "2018",
month = "2",
day = "1",
doi = "10.2174/1570179414666170525103947",
language = "English",
volume = "15",
pages = "105--109",
journal = "Current Organic Synthesis",
issn = "1570-1794",
publisher = "Bentham Science Publishers",
number = "1",

}

Norouzi-Arasi, H, Salom-Roig, XJ, Lanners, S & Hanquet, G 2018, 'First total synthesis of pamamycin-621D', Current Organic Synthesis, VOL. 15, Numéro 1, p. 105-109. https://doi.org/10.2174/1570179414666170525103947

First total synthesis of pamamycin-621D. / Norouzi-Arasi, Hassan; Salom-Roig, Xavier J.; Lanners, Steve; Hanquet, Gilles.

Dans: Current Organic Synthesis, Vol 15, Numéro 1, 01.02.2018, p. 105-109.

Résultats de recherche: Contribution à un journal/une revueArticle

TY - JOUR

T1 - First total synthesis of pamamycin-621D

AU - Norouzi-Arasi, Hassan

AU - Salom-Roig, Xavier J.

AU - Lanners, Steve

AU - Hanquet, Gilles

PY - 2018/2/1

Y1 - 2018/2/1

N2 - Aim and Objective: The objective of our work was to synthesize and fully characterize Pamamycin-621D, one of the less abundant members of a large family of macrodiolides with antimycobacterial properties, which had never been synthesized before. Furthermore, we also wished to improve our general strategy by using a new unsaturated precursor. Material and Method: A new unsaturated ethylketone precursor was prepared using alkene cross metathesis, and a convergent and flexible strategy based on a key diastereoselective aldol addition was implemented to afford pamamycin-621D in 12 steps from that precursor. Results: Pamamycin-621D has been obtained and fully characterized for the first time. The structure of pamamycin-621D was confirmed by HRMS and comparison of1H-NMR spectra with the natural pamamycin-621D. Both optical rotation and13C-NMR had not been published previously due to lack of material, and the latter are reported here for the first time. Given the scarce characterization available previously, our synthesis also gives additional support to the initial structural assignment of pamamycin-621D. A significant improvement of the key aldol addition via the use of a new unsaturated precursor is also reported. Conclusion: The work described above constitutes the first total synthesis of pamamycin-621D and has enabled us to fully characterize this scarcely available natural product. More importantly, this work highlights the fact that our synthetic approach provides ready access to various members of the pamamycin family, allowing possible studies on structure-activity relationships and mode of action of even the least abundant of these natural products. The synthesis of other pamamycin congeners and biological investigations will be published in due course.

AB - Aim and Objective: The objective of our work was to synthesize and fully characterize Pamamycin-621D, one of the less abundant members of a large family of macrodiolides with antimycobacterial properties, which had never been synthesized before. Furthermore, we also wished to improve our general strategy by using a new unsaturated precursor. Material and Method: A new unsaturated ethylketone precursor was prepared using alkene cross metathesis, and a convergent and flexible strategy based on a key diastereoselective aldol addition was implemented to afford pamamycin-621D in 12 steps from that precursor. Results: Pamamycin-621D has been obtained and fully characterized for the first time. The structure of pamamycin-621D was confirmed by HRMS and comparison of1H-NMR spectra with the natural pamamycin-621D. Both optical rotation and13C-NMR had not been published previously due to lack of material, and the latter are reported here for the first time. Given the scarce characterization available previously, our synthesis also gives additional support to the initial structural assignment of pamamycin-621D. A significant improvement of the key aldol addition via the use of a new unsaturated precursor is also reported. Conclusion: The work described above constitutes the first total synthesis of pamamycin-621D and has enabled us to fully characterize this scarcely available natural product. More importantly, this work highlights the fact that our synthetic approach provides ready access to various members of the pamamycin family, allowing possible studies on structure-activity relationships and mode of action of even the least abundant of these natural products. The synthesis of other pamamycin congeners and biological investigations will be published in due course.

KW - Aldol reaction

KW - Cross metathesis

KW - Macrodiolides

KW - Natural products

KW - Pamamycin

KW - Total synthesis

UR - http://www.scopus.com/inward/record.url?scp=85045979150&partnerID=8YFLogxK

U2 - 10.2174/1570179414666170525103947

DO - 10.2174/1570179414666170525103947

M3 - Article

AN - SCOPUS:85045979150

VL - 15

SP - 105

EP - 109

JO - Current Organic Synthesis

JF - Current Organic Synthesis

SN - 1570-1794

IS - 1

ER -