@article{25c4c8aba36c4c2c99aede0b87b407bd,
title = "Total synthesis of (+)-spiroindimicin A and congeners unveils their antiparasitic activity",
abstract = "The spiroindimicins are a unique class of chlorinated indole alkaloids characterized by three heteroaromatic rings structured around a congested spirocyclic stereocenter. Here, we report the first total synthesis of (+)-spiroindimicin A, which bears a challenging C-3′/C-5′′-linked spiroindolenine. We detail our initial efforts to effect a biomimetic oxidative spirocyclization from its proposed natural precursor, lynamicin D, and describe how these studies shaped our final abiotic 9-step solution to this complex alkaloid built around a key Pd-catalyzed asymmetric spirocyclization. Scalable access to spiroindimicins A, H, and their congeners has enabled discovery of their activity against several parasites relevant to human health, providing potential starting points for new therapeutics for the neglected tropical diseases leishmaniasis and African sleeping sickness.",
author = "Zhen Zhang and Sneha Ray and Leah Imlay and Callaghan, {Lauren T.} and Hanspeter Niederstrasser and Mallipeddi, {Prema Latha} and Posner, {Bruce A.} and Wetzel, {Dawn M.} and Phillips, {Margaret A.} and Smith, {Myles W.}",
note = "Funding Information: This work was nancially supported by UT Southwestern through the W. W. Caruth Jr. Scholarship. Funding from the Welch Foundation to M. W. S. (I-2045), M. A. P. (I-1257), and D. M. W. (I-2086) is gratefully acknowledged. This work was also partially funded by the NIH grants, R01AI103947 (to M. A. P), R01AI146349 (to D. M. W.), and 1S10OD026758-01 (to B. A. P.), as well as by the Children's Clinical Research Advisory Committee Early Investigator Award, 2019 Harrington Scholar-Innovator Award, and 2020 UTSW Circle of Friends Pilot Synergy Grant (all to D. M. W.). We thank Dr Fan Xu for attempting electrochemical and photoredox spirocyclizations of 12 and its protected variants. We are grateful to Prof. Chang-seng Zhang, Dr Liang Ma, and Wenjun Zhang (South China University of Oceanology) for providing spectra and an authentic sample of SPM A, and Prof. Peter K{\"u}ndig (Universit{\'e} de Gen{\`e}ve) for providing chiral NHC precursors. We thank the Tambar, Ready, Qin, DeBrabander, Chen, and Falck groups (UT Southwestern) for generous access to equipment and chemicals, as well as helpful discussions, and Dr Feng Lin for assistance with NMR studies. Funding Information: This work was financially supported by UT Southwestern through the W. W. Caruth Jr. Scholarship. Funding from the Welch Foundation to M. W. S. (I-2045), M. A. P. (I-1257), and D. M. W. (I-2086) is gratefully acknowledged. This work was also partially funded by the NIH grants, R01AI103947 (to M. A. P), R01AI146349 (to D. M. W.), and 1S10OD026758-01 (to B. A. P.), as well as by the Children's Clinical Research Advisory Committee Early Investigator Award, 2019 Harrington Scholar-Innovator Award, and 2020 UTSW Circle of Friends Pilot Synergy Grant (all to D. M. W.). We thank Dr Fan Xu for attempting electrochemical and photoredox spirocyclizations of12and its protected variants. We are grateful to Prof. Changseng Zhang, Dr Liang Ma, and Wenjun Zhang (South China University of Oceanology) for providing spectra and an authentic sample of SPM A, and Prof. Peter K{\"u}ndig (Universit{\'e} de Gen{\`e}ve) for providing chiral NHC precursors. We thank the Tambar, Ready, Qin, DeBrabander, Chen, and Falck groups (UT Southwestern) for generous access to equipment and chemicals, as well as helpful discussions, and Dr Feng Lin for assistance with NMR studies. Publisher Copyright: {\textcopyright} The Royal Society of Chemistry 2021.",
year = "2021",
month = aug,
day = "14",
doi = "10.1039/d1sc02838c",
language = "English (US)",
volume = "12",
pages = "10388--10394",
journal = "Chemical Science",
issn = "2041-6520",
publisher = "Royal Society of Chemistry",
number = "30",
}