A Convergent Total Synthesis of the Kedarcidin Chromophore: 20-Years in the Making

Lear, Martin and Hirai, Keiichiro and Ogawa, Kouki and Yamashita, Shinji and Hirama, Masahiro (2019) A Convergent Total Synthesis of the Kedarcidin Chromophore: 20-Years in the Making. Journal of Antibiotics . ISSN 0021-8820

Full content URL: https://doi.org/10.1038/s41429-019-0175-y

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A Convergent Total Synthesis of the Kedarcidin Chromophore: 20-Years in the Making
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Abstract

The kedarcidin chromophore is a formidible target for total synthesis. Herein, we
19 describe a viable synthesis of this highly unstable natural product. This entailed the early
20 introduction and gram-scale synthesis of 2-deoxysugar conjugates of both L-mycarose and L21
kedarosamine. Key advances include: (1) stereoselective allenylzinc keto-addition to form an
22 epoxyalkyne; (2) -selective glycosylations with 2-deoxy thioglycosides (AgPF6/DTBMP)
23 and Schmidt donors (TiCl4); (3) Mitsunobu aryl etherification to install a hindered 1,2-cis24
configuration; (4) atropselective and convergent Sonogashira-Shiina cyclization sequence;
25 (5) Ohfune-based amidation protocol for naphthoic acid; (6) Ce(III)-mediated nine26
membered enediyne cyclization and ester/mesylate derivatisation; (7) SmI2-based reductive
27 olefination and global HF-deprotection end-game. The longest linear sequence from gram28
scale intermediates is 17-steps, and HRMS data of the synthetic natural product was obtained
29 for the first time

Keywords:Total synthesis
Subjects:F Physical Sciences > F160 Organic Chemistry
Divisions:College of Science > School of Chemistry
ID Code:35003
Deposited On:11 Apr 2019 11:23

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