Journal of the American Chemical Society
The Supporting Information is available free of charge on
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7215, Exhibits Anti-Influenza Virus Properties Bioscience,
Biotechnology, and Biochemistry 2017, 81, 59.
Experimental procedures, analytical data, spectra (1H
NMR, 13C NMR and IR) and crystallographic data (CIF)
(3) Furusaki, A.; Matsumoto, T.; Ogura, H.; Takayanagi, H.;
Hirano, A.; Ōmura, S. J. X-Ray Crystal Structure of Herquline, a
New Biologically Active Piperazine from Penicillium herquei Fg-
372 C. S. Chem. Comm. 1980, 698.
AUTHOR INFORMATION
Corresponding Author
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(4)For Ph.D. theses describing efforts directed toward the
herqulines, see: (a) Kim, G. T. Ph.D. Thesis, Korea Advanced
Institute of Science and Technology, November 1997. (b) Hart, J.
M. Ph.D. Thesis, University of Leeds, June 2004. (c) Stawski, P.
S. Ph.D. Thesis, Ludwig-Maximilians-Universität München,
December 2012. (d) Yang, H. Ph.D Thesis, University of
Birmingham, August 2015.
* John_L_Wood@baylor.edu
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Author Contributions
#JBC and AK contributed equally to the completion of these
studies
(5) For conference proceedings describing efforts toward the
herqulines, see: Kawai, N.; Atsumi, T.; Arai, N.; Kuwajima, I.
Nippon Kagakkai, Koen Yokushu 2003, 83, 777.
Notes
The authors declare no competing financial interests.
(6) Yu, X.; Liu, F.; Zou, Y.; Tang, M.-C.; Hang, L.; Houk, K. N.;
Tang, Y. Biosynthesis of Strained Piperazine Alkaloids-
Uncovering the Concise Pathway of Herquline A J. Am. Chem.
Soc. 2016, 138, 13529.
ACKNOWLEDGMENT
The authors thank Dr. Sam Yruegas for her assistance in
obtaining and analyzing X-ray crystallographic data and
Professors Satoshi Ōmura and Toshiaki Sunazuka for
providing an authentic sample of herquline A. We also
acknowledge the gracious assistance of Professor Yi Tang
(UCLA) in providing authentic samples, biosynthetic
intermediates, and insight regarding their research efforts.
Dr. Jacob Timmerman is acknowledged for helpful
discussions. The authors would also like to thank
Professor Phil Baran for the collegial exchange of
information (ref. 18b) that occurred after our having
received reviews and submitted a revision of this
manuscript. Financial support was provided from Baylor
University, the Welch Foundation (Chair, AA-006), the
Cancer Prevention and Research Institute of Texas
(CPRIT, R1309), and the NSF (CHE-1764240). Finally,
the authors would like to dedicate this manuscript to
Professor E. J. Corey on the occasion of his 90th birthday.
(7) Tabulated and physical comparisons of the spectral data
reported for herquline B by Ōmura and Tang are included as
supporting information.
(8) Differentiation of the aryl rings in 6 as a phenol and anisole is
a strategic remnant of early investigations targeting 1. This
differentiation may not be necessary to access 2 and avoiding it
could lead to
a more efficient strategy; however, to date,
investigations along these lines have met with limited success.
(9)David, N.; Pasceri, R.; Kitson, R. R. A.; Pradal, A.; Moody, C.
J. Formal Total Synthesis of Diazonamide A by Indole Oxidative
Rearrangement Chem. Eur. J. 2016, 22, 10867.
(10)Krenitsky, P. J.; Boger, D. L. Synthesis of the (S,S,S)-
Diastereomer of the 15-Membered Biaryl Ring System of RP
66453 Tetrahedron Lett. 2003, 44, 4019.
REFERENCES
(11) Cochrane, J. R.; White, J. M.; Wille, U.; Hutton, C. A. Total
Synthesis of Mycocyclosin Org. Lett. 2012, 14, 2402. For a
recent modification of these coupling conditions, see: Zhu, X.;
McAtee, C. C.; Schindler, C. S. Scalable Synthesis of
Mycocyclosin Org. Lett. 2018, 20, 2862.
(1) (a) Ōmura, S.; Hirano, A.; Iwai, Y.; Masuma, R. Herquline, A New
Alkaloid Produced by Penicillium Herquei Fermentation, Isolation and
Properties J. Antibiot. 1979, 32, 786. (b) Enomoto, Y.; Shiomi, K.;
Hayashi, M.; Masuma, R.; Kawakubo, T.; Tomosawa, K.; Iwai, Y.;
Ōmura, S. Herquline B, a New Platelet Aggregation Inhibitor Produced
by Penicillium herquei Fg-372 J. Antibiot. 1996, 49, 50.
(12) The stereochemistry illustrated for 11 is based upon the
single crystal X-ray analysis of aziridine ii, a product formed while
attempting an alternative route that involved advancing i. These
data are included as supporting information.
(2) Chiba, T.; Asami, Y.; Suga, T.; Watanabe, Y.; Nagai, T.;
Momose, F.; Nonaka, K.; Iwatsuki, M.; Yamada, H.; Ōmura, S.;
Shiomi, K. Herquline A, Produced by Penicillium herquei FKI-
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