Abstract
The total syntheses of three drimane-type sesquiterpenoids, (-)-mnio-petal E, (-)-mniopetal F, and (-)-kuehneromycin A, are described. These na products innibit the enzymatic activity of RNA-directed DNA-polymerases (reverse transcriptases) of the human immunodeficiency virus (HIV)-1. Our enantiospeci total syntheses of these target molecules in naturally occurring forms commenced with a known 2,3-anhydro-D-arabinitol derivative, which was prepared using th Sharpless asymmetric epoxidation strategy. A combination of highly stereocontrolled inter- and intramolecular Horner-Emmons carbon elongations led to the tw butenolides tethering 1,2,4,9- and 1,4,9-functionalized nona-5,7-diene moieties at the β-carbon. The key step in mniopetal E synthesis is a stereoselective thermal intramolecular Diels-Alder reaction of the former butenolide compound, providing a highly oxygenated tricyclic skeleton with the desired endo an π-facial selections. The intramolecular Diels-Alder reaction of the latter butenolide compound for the syntheses of other two drimanes also proceeded with stereoselectivity, which is controlled by a balance of the steric effect and the stereoelectronic effect of a trialkylsilyloxy substituent existing adjacent t dienophile in accordance with Cieplak's theory. The transformation of the γ-lactone moiety in the cycloadducts to the γ-hydroxy-γ-lactone part was effic achieved via a tetracyclic intermediate. Our total syntheses of (-)-mniopetal E, (-)-mniopetal F, and (-)-kuehneromycin A established the unsettled absolute stereochemistries of the antibiotics. In addition, the reported total syntheses by Jauch are briefly reviewed.
| Original language | English |
|---|---|
| Pages (from-to) | 127-167 |
| Number of pages | 41 |
| Journal | Studies in Natural Products Chemistry |
| Volume | 29 |
| Issue number | PART J |
| DOIs | |
| Publication status | Published - 2003 |
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ASJC Scopus subject areas
- Organic Chemistry
- Drug Discovery
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Total synthesis of biologically intriguing drimane-type sesquiterpenoids via intramolecular diels-alder approaches. / Suzuki, Yoshikazu; Takao, Kenichi; Tadano, Kin Ichi.
In: Studies in Natural Products Chemistry, Vol. 29, No. PART J, 2003, p. 127-167.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Total synthesis of biologically intriguing drimane-type sesquiterpenoids via intramolecular diels-alder approaches
AU - Suzuki, Yoshikazu
AU - Takao, Kenichi
AU - Tadano, Kin Ichi
PY - 2003
Y1 - 2003
N2 - The total syntheses of three drimane-type sesquiterpenoids, (-)-mnio-petal E, (-)-mniopetal F, and (-)-kuehneromycin A, are described. These na products innibit the enzymatic activity of RNA-directed DNA-polymerases (reverse transcriptases) of the human immunodeficiency virus (HIV)-1. Our enantiospeci total syntheses of these target molecules in naturally occurring forms commenced with a known 2,3-anhydro-D-arabinitol derivative, which was prepared using th Sharpless asymmetric epoxidation strategy. A combination of highly stereocontrolled inter- and intramolecular Horner-Emmons carbon elongations led to the tw butenolides tethering 1,2,4,9- and 1,4,9-functionalized nona-5,7-diene moieties at the β-carbon. The key step in mniopetal E synthesis is a stereoselective thermal intramolecular Diels-Alder reaction of the former butenolide compound, providing a highly oxygenated tricyclic skeleton with the desired endo an π-facial selections. The intramolecular Diels-Alder reaction of the latter butenolide compound for the syntheses of other two drimanes also proceeded with stereoselectivity, which is controlled by a balance of the steric effect and the stereoelectronic effect of a trialkylsilyloxy substituent existing adjacent t dienophile in accordance with Cieplak's theory. The transformation of the γ-lactone moiety in the cycloadducts to the γ-hydroxy-γ-lactone part was effic achieved via a tetracyclic intermediate. Our total syntheses of (-)-mniopetal E, (-)-mniopetal F, and (-)-kuehneromycin A established the unsettled absolute stereochemistries of the antibiotics. In addition, the reported total syntheses by Jauch are briefly reviewed.
AB - The total syntheses of three drimane-type sesquiterpenoids, (-)-mnio-petal E, (-)-mniopetal F, and (-)-kuehneromycin A, are described. These na products innibit the enzymatic activity of RNA-directed DNA-polymerases (reverse transcriptases) of the human immunodeficiency virus (HIV)-1. Our enantiospeci total syntheses of these target molecules in naturally occurring forms commenced with a known 2,3-anhydro-D-arabinitol derivative, which was prepared using th Sharpless asymmetric epoxidation strategy. A combination of highly stereocontrolled inter- and intramolecular Horner-Emmons carbon elongations led to the tw butenolides tethering 1,2,4,9- and 1,4,9-functionalized nona-5,7-diene moieties at the β-carbon. The key step in mniopetal E synthesis is a stereoselective thermal intramolecular Diels-Alder reaction of the former butenolide compound, providing a highly oxygenated tricyclic skeleton with the desired endo an π-facial selections. The intramolecular Diels-Alder reaction of the latter butenolide compound for the syntheses of other two drimanes also proceeded with stereoselectivity, which is controlled by a balance of the steric effect and the stereoelectronic effect of a trialkylsilyloxy substituent existing adjacent t dienophile in accordance with Cieplak's theory. The transformation of the γ-lactone moiety in the cycloadducts to the γ-hydroxy-γ-lactone part was effic achieved via a tetracyclic intermediate. Our total syntheses of (-)-mniopetal E, (-)-mniopetal F, and (-)-kuehneromycin A established the unsettled absolute stereochemistries of the antibiotics. In addition, the reported total syntheses by Jauch are briefly reviewed.
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U2 - 10.1016/S1572-5995(03)80006-6
DO - 10.1016/S1572-5995(03)80006-6
M3 - Article
VL - 29
SP - 127
EP - 167
JO - Studies in Natural Products Chemistry
JF - Studies in Natural Products Chemistry
SN - 1572-5995
IS - PART J
ER -