Details
| Original language | English |
|---|---|
| Pages (from-to) | 5291-5298 |
| Number of pages | 8 |
| Journal | Chemistry - A European Journal |
| Volume | 23 |
| Issue number | 22 |
| Publication status | Published - 13 Feb 2017 |
Abstract
The polyketide, 20-deoxy elansolid B1, was prepared by a convergent strategy that relied on a putative biomimetic intramolecular Diels–Alder cycloaddition (IMDA) via a vinylic p-quinone methide intermediate to furnish the key tetrahydroindane unit. The (Z,E,Z)-configured triene unit was constructed by Pd-catalyzed Suzuki–Miyaura and Stille cross-coupling reactions without isomerization of any of the olefinic double bonds. Formation of a p-methide quinone intermediate under basic conditions and subsequent Michael addition by water to this intermediate proceeded with high facial selectivity which terminated this total synthesis. Remarkably, the new elansolid derivative 2 c shows very good inhibitory effect against Bacillus subtilis and Staphylococcus aureus (including MRSA) similarly to the best elansolid derivatives reported so far. Consequently, the hydroxyl group at C20 is not essential for antibacterial activity.
Keywords
- antibiotics, biosynthesis, intramolecular Diels–Alder cycloaddition, polyketides, total synthesis
ASJC Scopus subject areas
- Chemical Engineering(all)
- Catalysis
- Chemistry(all)
- Organic Chemistry
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In: Chemistry - A European Journal, Vol. 23, No. 22, 13.02.2017, p. 5291-5298.
Research output: Contribution to journal › Article › Research › peer review
}
TY - JOUR
T1 - Harnessing a p-Quinone Methide Intermediate in the Biomimetic Total Synthesis of the Highly Active Antibiotic 20-Deoxy-Elansolid B1
AU - Wang, Liangliang
AU - Candito, David
AU - Dräger, Gerald
AU - Herrmann, Jennifer
AU - Müller, Rolf
AU - Kirschning, Andreas
N1 - Funding information: The work was funded by the Deutsche Forschungsgemeinschaft (Cluster of Excellence REBIRTH; ?From Regenerative Biology to Reconstructive Therapy? EXC 62). We thank the Alexander-von-Humboldt Foundation for providing a postdoc scholarship for D. Candito. The work was funded by the Deutsche Forschungsgemeinschaft (Cluster of Excellence REBIRTH; “From Regenerative Biology to Reconstructive Therapy” EXC 62). We thank the Alexander-von-Humboldt Foundation for providing a postdoc scholarship for D. Candito.
PY - 2017/2/13
Y1 - 2017/2/13
N2 - The polyketide, 20-deoxy elansolid B1, was prepared by a convergent strategy that relied on a putative biomimetic intramolecular Diels–Alder cycloaddition (IMDA) via a vinylic p-quinone methide intermediate to furnish the key tetrahydroindane unit. The (Z,E,Z)-configured triene unit was constructed by Pd-catalyzed Suzuki–Miyaura and Stille cross-coupling reactions without isomerization of any of the olefinic double bonds. Formation of a p-methide quinone intermediate under basic conditions and subsequent Michael addition by water to this intermediate proceeded with high facial selectivity which terminated this total synthesis. Remarkably, the new elansolid derivative 2 c shows very good inhibitory effect against Bacillus subtilis and Staphylococcus aureus (including MRSA) similarly to the best elansolid derivatives reported so far. Consequently, the hydroxyl group at C20 is not essential for antibacterial activity.
AB - The polyketide, 20-deoxy elansolid B1, was prepared by a convergent strategy that relied on a putative biomimetic intramolecular Diels–Alder cycloaddition (IMDA) via a vinylic p-quinone methide intermediate to furnish the key tetrahydroindane unit. The (Z,E,Z)-configured triene unit was constructed by Pd-catalyzed Suzuki–Miyaura and Stille cross-coupling reactions without isomerization of any of the olefinic double bonds. Formation of a p-methide quinone intermediate under basic conditions and subsequent Michael addition by water to this intermediate proceeded with high facial selectivity which terminated this total synthesis. Remarkably, the new elansolid derivative 2 c shows very good inhibitory effect against Bacillus subtilis and Staphylococcus aureus (including MRSA) similarly to the best elansolid derivatives reported so far. Consequently, the hydroxyl group at C20 is not essential for antibacterial activity.
KW - antibiotics
KW - biosynthesis
KW - intramolecular Diels–Alder cycloaddition
KW - polyketides
KW - total synthesis
UR - http://www.scopus.com/inward/record.url?scp=85017275797&partnerID=8YFLogxK
U2 - 10.1002/chem.201605884
DO - 10.1002/chem.201605884
M3 - Article
C2 - 28195370
AN - SCOPUS:85017275797
VL - 23
SP - 5291
EP - 5298
JO - Chemistry - A European Journal
JF - Chemistry - A European Journal
SN - 0947-6539
IS - 22
ER -