literature report 7 asymmetric total synthesis of neooxazolomycin › __local › 1 › 9c › 40...
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Literature Report 7
Reporter:
Checker:
Date:
Kim, S. et al. Angew. Chem. Int. Ed. 2019, 58, 11018.
Hatakeyama, S. et al. Angew. Chem. Int. Ed. 2007, 46, 6703.
Zi-Biao Zhao
Xiao-Yong Zhai
2019-9-23
Asymmetric Total Synthesis of
Neooxazolomycin
+
Background:
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Research:
Total synthesis of natural products.
Medicinal chemistry and drug discovery.
Electrochemical & photochemical bioorganic chemistry.
1984-1988 B.S., Seoul National University
1988-1990 M.S., Seoul National University
1991-1992 Chemistry Research Scientist (Korea Institute of
Science and Technology)
1992-1997 Ph.D., University of Pennsylvania (Jeffrey D. Winkler)
1997-1998 Postdoc., The Scripps Research Institute (K.C. Nicolaou)
1998-1999 Senior Research Scientist (Abbott Laboratories)
1999-2008 Associate Professor, Seoul National University
2008-Now Professor, Seoul National University
CV of Prof. Sanghee. Kim
Contents
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1
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Introduction
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Total Synthesis of Neooxazolomycin by Hatakeyama
Summary
Total Synthesis of Neooxazolomycin by Kim
Introduction
Neooxazolomycin was isolated from Streptomyces by Uemura in 1985.
Neooxazolomycin possesses lactam-lactone systems and polyene subunit.
These oxazolomycins exhibit a wide range of potent antibacterial and
antiviral activities as well as in vivo antitumor activity.
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Uemura, D. et al. Tetrahedron Lett. 1985, 26, 1077.
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Retrosynthetic Analysis (Hatakeyama’s Work)
Hatakeyama, S. et al. Angew. Chem. Int. Ed. 2007, 46, 6703.
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Retrosynthetic Analysis
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Total Synthesis of Neooxazolomycin
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Total Synthesis of Neooxazolomycin
Nozaki-Hiyama-Kishi Reaction
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R1 = 烯基、芳基、烯丙基、乙烯基、丙炔基，炔基
R2 = R3 = 芳基、烷基、烯基、氢; X = Cl, Br, I, OTf
Solvent = DMF, DMSO, THF
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Total Synthesis of Neooxazolomycin
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Total Synthesis of Neooxazolomycin
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Retrosynthetic Analysis (Kim’s Work)
Kim, S. et al. Angew. Chem. Int. Ed. 2019, 58, 11018.
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Retrosynthetic Analysis
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Total Synthesis of Neooxazolomycin
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Total Synthesis of Neooxazolomycin
Horner-Wadsworth-Emmons Reaction (HWE)
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动力学
热力学
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Total Synthesis of Neooxazolomycin
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Total Synthesis of Neooxazolomycin
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Total Synthesis of Neooxazolomycin
Corey-Fuchs Reaction
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Total Synthesis of Neooxazolomycin
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Total Synthesis of Neooxazolomycin
Summary
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25 steps and 1.3% overall yield
Chirality propagation processes
Palladium-catalyzed hydrogenolysis, Stille reaction
Hatakeyama ’s Work:
20 steps and 2.9% overall yield
Hydrosilylation, Palladium-catalyzed alkenylation
Dihydroxylation, Nozaki–Hiyama–Kishi reaction
Kim’ s Work:
The First Paragraph
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Oxazolomycins are structurally unique natural products that are characterized
by fused- or spiro-bicyclic lactamlactone systems, as well as a polyene subunit.
Since the isolation of (+)-neooxazolomycin in 1985, a number of members of
this family have been identified, including oxazolomycins A-C, oxazolomycin
A2, bisoxazolomycin A, 16-methyloxazolomycin, curromycins A and B, KSM-
2690 B–C, and lajollamycins A–D. These oxazolomycins exhibit a wide range
of potent antibacterial and antiviral activities as well as in vivo antitumor activity.
Because of their structural complexity and potent biological activities,
considerable attention has been paid to their synthesis. However, there are
only a few reports on the successful total syntheses of oxazolomycins.
In summary, we have accomplished the asymmetric total synthesis of
(+)-neooxazolomycin using a minimum number of chiral sources. The
right-hand fragment with six stereocenters was synthesized from D-
serine as the only chiral source. Several chirality propagation processes
were employed, including MOC, DKR, and substrate-controlled
asymmetric inductions. The only chirality present in the left-hand
fragment was installed by the asymmetric reduction of a ketone. The
Z,Z,E-configured triene unit was stereoselectively constructed using
metal-assisted reactions such as a cuprate addition, a Pd-catalyzed
hydrogenolysis of a dibromoalkene, and a Stille reaction. This synthesis
is an exceptionally attractive strategy in terms of its chiral economy. The
use of this efficient strategy for the synthesis of other oxazolomycins is
The Last Paragraph
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currently under investigation.
Acknowledgement
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