Total synthesis of 6-Deoxyerethronolide B

CHEM 635Kelsey Roberts

05/07/13

Gao, X.; Woo, S.K.; Krische M.J. J. Am. Chem. Soc. 2013, 135, 4223

Michael J. Krische• 1989- BS in Chemistry

University of California Berkley• 1996- PhD Stanford University

under Dr. Barry M. Trost• 1997-1999- NIH Post Doc Dr.

Jean-Marie Lehn• 1999-2003- Assistant Professor

at University of Texas Austin• 2004-Present- Full Professor• Multiple Awards• 175 + Publications• Research focuses on:“catalytic reaction development

with attendant applications in natural product synthesis.”

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6-Deoxyerythronolide B

• 14 Membered Macrolide• Other reported syntheses over 20 Longest linear steps• Biogenic precursor to Erythromycin A and B, Erythronolide A and

B, and (9S)-Dihydroerythronolide A

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Retrosynthesis

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A B

Synthesis of Portion A

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(S)-SEGPHOSChiral acid

Synthesis of Portion A Continued

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Synthesis of Portion B

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Combining Both Sides

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Conclusion

• 14 Longest Linear Steps• 20 Total Steps• First use of two methods for alcohol CH-crotylation via transfer

hydrogenation in total synthesis. • Most concise construction of any erythronolide previously reported

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