C-H Functionalization-Enabled 11-Step Semisynthesis of (-)-Veragranine A and Characterization of Synthetic Analogs in Osteoarthritis-related Pain Treatment
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Standard
C-H Functionalization-Enabled 11-Step Semisynthesis of (-)-Veragranine A and Characterization of Synthetic Analogs in Osteoarthritis-related Pain Treatment. / Ma, Donghui; Duran, Paz; Al-Ahmad, Reem; Hestehave, Sara; Joa, Margarita; Alsbiei, Omar; Rodríguez-Palma, Erick J; Li, Yanrong; Wang, Shilin; Khanna, Rajesh; Dai, Mingji.
I: Journal of the American Chemical Society, 2024.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - C-H Functionalization-Enabled 11-Step Semisynthesis of (-)-Veragranine A and Characterization of Synthetic Analogs in Osteoarthritis-related Pain Treatment
AU - Ma, Donghui
AU - Duran, Paz
AU - Al-Ahmad, Reem
AU - Hestehave, Sara
AU - Joa, Margarita
AU - Alsbiei, Omar
AU - Rodríguez-Palma, Erick J
AU - Li, Yanrong
AU - Wang, Shilin
AU - Khanna, Rajesh
AU - Dai, Mingji
PY - 2024
Y1 - 2024
N2 - We report an efficient semisynthesis of the cholestane steroidal alkaloid (-)-veragranine A with a 6/6/6/5/6/6 hexacyclic ring system, eight stereocenters, and a unique C12-C23 linkage. Our synthesis features a Schönecker-Baran C-H oxidation at C12, a Suzuki-Miyaura cross-coupling to form the C12-C23 bond, and a hydrogen atom transfer (HAT)-initiated Minisci C-H cyclization to forge the C20-C22 bond with desired stereochemistry at C20. These enabling transformations significantly enhanced the overall synthetic efficiency and delivered (-)-veragranine A in 11 steps and over 200 mg from cheap and readily available dehydroepiandrosterone. In addition, this approach allowed flexible syntheses of novel synthetic analogs for biological evaluations in sensory neurons in vitro and in an in vivo model of arthritic pain, from which two novel lead compounds were identified for further development.
AB - We report an efficient semisynthesis of the cholestane steroidal alkaloid (-)-veragranine A with a 6/6/6/5/6/6 hexacyclic ring system, eight stereocenters, and a unique C12-C23 linkage. Our synthesis features a Schönecker-Baran C-H oxidation at C12, a Suzuki-Miyaura cross-coupling to form the C12-C23 bond, and a hydrogen atom transfer (HAT)-initiated Minisci C-H cyclization to forge the C20-C22 bond with desired stereochemistry at C20. These enabling transformations significantly enhanced the overall synthetic efficiency and delivered (-)-veragranine A in 11 steps and over 200 mg from cheap and readily available dehydroepiandrosterone. In addition, this approach allowed flexible syntheses of novel synthetic analogs for biological evaluations in sensory neurons in vitro and in an in vivo model of arthritic pain, from which two novel lead compounds were identified for further development.
U2 - 10.1021/jacs.4c04025
DO - 10.1021/jacs.4c04025
M3 - Journal article
C2 - 38843262
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
SN - 0002-7863
ER -
ID: 394713779