C-H Functionalization-Enabled 11-Step Semisynthesis of (-)-Veragranine A and Characterization of Synthetic Analogs in Osteoarthritis-related Pain Treatment

Research output: Contribution to journal › Journal article › Research › peer-review

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.

In: Journal of the American Chemical Society, 2024.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Ma, D, Duran, P, Al-Ahmad, R, Hestehave, S, Joa, M, Alsbiei, O, Rodríguez-Palma, EJ, Li, Y, Wang, S, Khanna, R & Dai, M 2024, 'C-H Functionalization-Enabled 11-Step Semisynthesis of (-)-Veragranine A and Characterization of Synthetic Analogs in Osteoarthritis-related Pain Treatment', Journal of the American Chemical Society. https://doi.org/10.1021/jacs.4c04025

APA

Ma, D., Duran, P., Al-Ahmad, R., Hestehave, S., Joa, M., Alsbiei, O., Rodríguez-Palma, E. J., Li, Y., Wang, S., Khanna, R., & Dai, M. (2024). C-H Functionalization-Enabled 11-Step Semisynthesis of (-)-Veragranine A and Characterization of Synthetic Analogs in Osteoarthritis-related Pain Treatment. Journal of the American Chemical Society. https://doi.org/10.1021/jacs.4c04025

Vancouver

Ma D, Duran P, Al-Ahmad R, Hestehave S, Joa M, Alsbiei O et al. C-H Functionalization-Enabled 11-Step Semisynthesis of (-)-Veragranine A and Characterization of Synthetic Analogs in Osteoarthritis-related Pain Treatment. Journal of the American Chemical Society. 2024. https://doi.org/10.1021/jacs.4c04025

Author

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. / C-H Functionalization-Enabled 11-Step Semisynthesis of (-)-Veragranine A and Characterization of Synthetic Analogs in Osteoarthritis-related Pain Treatment. In: Journal of the American Chemical Society. 2024.

Bibtex

@article{8fa8fabc9da14537bd428ea590e1181e,
title = "C-H Functionalization-Enabled 11-Step Semisynthesis of (-)-Veragranine A and Characterization of Synthetic Analogs in Osteoarthritis-related Pain Treatment",
abstract = "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 Sch{\"o}necker-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.",
author = "Donghui Ma and Paz Duran and Reem Al-Ahmad and Sara Hestehave and Margarita Joa and Omar Alsbiei and Rodr{\'i}guez-Palma, {Erick J} and Yanrong Li and Shilin Wang and Rajesh Khanna and Mingji Dai",
year = "2024",
doi = "10.1021/jacs.4c04025",
language = "English",
journal = "Journal of the American Chemical Society",
issn = "0002-7863",
publisher = "ACS Publications",

}

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