Scheme 3. Completion of the total synthesis of 1 and 2. Reagents and conditions: (a) 2 M aq. HCl, acetone/THF, rt, 3 d, 94%; (b) 4, 2nd-generation Grubbs
catalyst, CH2Cl2, reflux, 1.5 h, 71%; (c) SiO2, 100 °C, ca. 900 Pa, 20 min, 85%; (d) (MeCN)2PdCl2, THF, 0 °C, 10 min, 70%.
In conclusion, the first total synthesis of asporyzin C (2) has been accomplished from the known Wieland–Miescher ketone
derivative 7 by a 13-step sequence that involves the highly diastereoselective installation of the -oriented C3-methyl group (7 → 14 →
5), Pd(II)-mediated oxidative indole ring formation (15 → 3), and cross-metathesis to construct the side chain moiety (16 → 17). The
exclusively diastereoselective ring closure of 2 to complete the first total synthesis of JBIR-03 (1) was efficiently achieved by Pd(II)-
catalyzed tetrahydrofuran ring formation. Synthetic studies on related indole diterpenes such as asporyzins A and B are also in progress,
and will be reported in due course.
Acknowledgments
This work was financially supported by the Platform Project for Supporting Drug Discovery and Life Science Research funded by
Japan Agency for Medical Research and Development (AMED). We are grateful to Drs. Kazuo Shin-ya and Takuya Hashimoto (AIST)
for providing the NMR spectra of natural JBIR-03. Thanks are also due to Ms. Yuka Taguchi (Tohoku University) for her help with
NMR and MS measurements.
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