Kang Hyun Jung
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Kang Hyun Jung. Introduction. Leucascandrolide A ( 1 , Scheme 1) was isolated in 1996 from the calcareous sponge Leucascandra caveolata , collected off the east coast of New Caledonia, by Pietra and co-workers.

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Kang Hyun Jung

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Kang hyun jung

Kang Hyun Jung


Kang hyun jung

Introduction

Leucascandrolide A (1, Scheme 1) was isolated in 1996 from the calcareous sponge Leucascandra caveolata,

collected off the east coast of New Caledonia, by Pietra and co-workers.

- This polyoxygenated 18-membered macrolide features two trisubstituted tetrahydropyran rings, one of

which has an unusual oxazole-bearing unsaturated side chain.

- Biological studies revealed potent cytotoxic activity against a range of cancer cell lines (IC50¼0.05 and

0.25 mgmL1 against KB oral epidermoid carcinoma and P388 leukemia cell lines, respectively), as well

as pronounced antifungal activity.


Kang hyun jung

Retro-Synthetic Analysis


Kang hyun jung

Preparation of Advanced Intermediate 18


Kang hyun jung

Jacobson Asymmetric Hetero Diels-Alder Reaction [1]


Kang hyun jung

HgII-Mediated Hydration of Alkyne [2]

- Alkynes are less basic than alkenes, Hg(OAc)2 (Hg+2 is a Lewis acid) is added to ensure complete reaction


Kang hyun jung

1,5-Anti Stereoindution in the Boron-Mediated Aldol Reaction[3]

Org. Lett.,4, 4325-4328, 2002


Kang hyun jung

1,3-Anti Reduction of β-Hydroxy Ketone[4]

J. Am. Chem. Soc., 110, 11, 3560-3578, 1988


Kang hyun jung

Selective Iodine(III)/TEMPO-Mediated Oxidation [5]

J. Org. Chem., 62, 6974-6977, 1997


Kang hyun jung

Elaboration to the Macrocyclic Core 24


Kang hyun jung

DIBAL Reduction and in situ Acetylation [6]

J. Org. Chem., 61, 8317-8320, 1996


Kang hyun jung

1,3-Asymmetric redution [7]


Kang hyun jung

Mistunobu Macrolactonization (Esterification)[8]

Synthesis, 1, 1981


Kang hyun jung

Preparation of the Oxazole-bearing Side Chain 3


Kang hyun jung

α-Alkylation of Hydrazone and Alkyl halide [9]


Kang hyun jung

Sonogashira Coupling of Functionalized Trifloyl Oxazole [10]

Org. Lett.,4, 2485-2488, 2002


Kang hyun jung

Completion of the Total Synthesis of Leucascandrolide A


Kang hyun jung

Lindlar Hydrogenation [11]


Kang hyun jung

Conclusion

  • In summary, we have completed a highly stereocontrolled synthesis

  • of the potent cytotoxic macrolide leucascandrolide A, proceeding in

  • 23 steps from 8 (longest linear sequence) and 5.3% overall yield. Key

  • features include a Jacobsen asymmetric hetero Diels-Alder reaction

  • to configure the right-hand tetrahydropyran ring, a 1,5-anti aldol

  • coupling, control over the C17 hydroxy center, and two sequential

  • Mitsunobu reactions, to close the 18-membered macrolactone and

  • append the oxazole-bearing side chain, respectively.


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