Organic Letters
Letter
dibromination5 of 32 were carried out according to the known
methods to deliver (−)-hamigeran B (3) and (−)-4-
bromohamigeran B (4), respectively, in high yield. The NMR
spectroscopic data and optical rotations of our synthesized
(−)-hamigeran B ([α]D20 −164.7 (c 0.15, CH2Cl2)) and (−)-4-
bromohamigeran B ([α]D20 −85.0 (c 0.37, CH2Cl2)) were close
to those of the corresponding natural products ([α]D25 −151.1 (c
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25
0.15, CH2Cl2)) for hamigeran B and [α]D −81.2 (c 0.37,
CH2Cl2) for 4-bromohamigeran B,1a respectively.
In conclusion, we have established a concise route for the
synthesis of (−)-hamigeran B (3) and (−)-4-bromohamigeran B
(4) that proceeds via a 13-step sequence from the known chiral
hydroxy ketone 18 (15 steps from commercially available 2-
methyl 1,3-diketone). To the best of our knowledge, this
synthetic route represents one of the very few that can
accomplish the synthesis of hamigeran B and 4-bromohamigeran
B within 15 steps either from a known compound or from
commercial material. Moreover, most of the transformations
employed herein could be performed on multigram scale. This
makes our synthetic route highly useful for the large scale
synthesis of both compounds, and, ultimately, for supplying
sufficient samples for an in-depth investigation of their biological
properties. Further optimization of the synthetic procedure
toward a large scale synthesis is currently underway in our lab.
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ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
■
S
Detailed experimental procedures, characterization data,
the copies of NMR spectra, and HPLC charts (PDF)
AUTHOR INFORMATION
Corresponding Authors
■
ORCID
(17) Xu, S.; Toyama, T.; Nakamura, J.; Arimoto, H. Tetrahedron Lett.
2010, 51, 4534.
Author Contributions
⊥B.-C.C. and G.-J.W. contributed equally.
(18) (a) Ishiyama, T.; Takagi, J.; Ishida, K.; Miyaura, N.; Anastasi, N.
R.; Hartwig, J. F. J. Am. Chem. Soc. 2002, 124, 390. (b) Boller, T. M.;
Murphy, J. M.; Hapke, M.; Ishiyama, T.; Miyaura, N.; Hartwig, J. F. J.
Am. Chem. Soc. 2005, 127, 14263. (c) Murphy, J. M.; Tzschucke, C. C.;
Hartwig, J. F. Org. Lett. 2007, 9, 757. (d) Murphy, J. M.; Liao, X.;
Hartwig, J. F. J. Am. Chem. Soc. 2007, 129, 15434.
Notes
(19) (a) Guan, J.; Wu, G.-J.; Han, F.-S. Chem. - Eur. J. 2014, 20, 3301.
(b) Du, Z.-J.; Guan, J.; Wu, G.-J.; Xu, P.; Gao, L.-X.; Han, F.-S. J. Am.
Chem. Soc. 2015, 137, 632. (c) Wu, G.-J.; Han, F.-S.; Zhao, Y.-L. RSC
Adv. 2015, 5, 69776. (d) Wu, G.-J.; Zhang, Y.-H.; Tan, D.-X.; Han, F.-S.
Nat. Commun. 2018, 9, 2148.
(20) (a) Nayak, M. K.; Chakraborti, A. K. Tetrahedron Lett. 1997, 38,
8749. (b) Hansson, C.; Wickberg, B. Synthesis 1976, 1976, 191.
(21) Casnati, G.; Pochini, A.; Terenghi, M. G.; Ungaro, R. J. Org. Chem.
1983, 48, 3783.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
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Financial support from NSFC (21602215, 21572215) and the
Engineering Research Center of Marine Bioresources Compre-
hensive Utilization of SOA (MBRCU201604) is acknowledged.
REFERENCES
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(22) Pilgrim, B. S.; Donohoe, T. J. J. Org. Chem. 2013, 78, 2149 and
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