- A New Approach to Models of the 4,5-Dihydroxycyclopentenone Core of the Kodaistatins A–D: Elucidation of the Diol Configuration in Kodaistatin A
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The kodaistatins A–D are strongly anti-diabetic natural products from Aspergillus terreus that hold some promise of a novel diabetes cure. However, considerations of that kind face two drawbacks: 1) The kodaistatins A–D contain a heavily substituted pulvinone/cyclopentenone combination; 2) they are 1,2-diols, the 3D structures of which have not been assigned yet. However, we can exclude two of the four possible stereostructures. We conclude that kodaistatin A is a trans-, not a cis-diol from NMR comparisons with a pair of cis, trans-isomeric kodaistatin models, which we synthesized in 11 and 12 steps, respectively. The stereocenters of the diol moiety arose from stereocomplementary, highly diastereoselective aldol additions of a lithium enolate or the corresponding silyl ketene acetal. The cyclopentenone moieties stemmed from intramolecular aldol additions and ensuing dehydrations. The requisite enolates were obtained by the reduction of α-bromoketones with samarium diiodide.
- Peter, David,Brückner, Reinhard
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- In vitro metabolism of chloroprene: Species differences, epoxide stereochemistry and a de-chlorination pathway
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Chloroprene (1) was metabolized by liver microsomes from Sprague-Dawley rats, Fischer 344 rats, B6C3F1 mice, and humans to the monoepoxides, (1-chloro-ethenyl)oxirane (5a/5b), and 2-chloro-2-ethenyloxirane (4a/4b). The formation of 4a/4b was inferred from the identification of their degradation products. With male Sprague-Dawley and Fischer 344 rat liver microsomes, there was a ca. 3:2 preference for the formation of (R)-(1-chloroethenyl)oxirane (5a) compared to the (S)-enantiomer (5b). A smaller but distinct enantioselectivity in the formation of (S)-(1-chloro-ethenyl)oxirane occurred with liver microsomes from male mouse (R:S, 0.90:1) or male human (R:S, 0.86:1). 2-Chloro-2-ethenyloxirane was very unstable in the presence of the microsomal mixture and was rapidly converted to 1-hydroxybut-3-en-2-one (11) and 1-chlorobut-3-en-2-one (12). An additional rearrangement pathway of 2-chloro-2-ethenyloxirane gave rise to 2-chlorobut-3-en-1-al (14) and 2-chlorobut-2-en-1-al (15). Further reductive metabolism of these metabolites occurred to form 1-hydroxybutan-2-one (17) and 1-chlorobutan-2-one (18). In the absence of an epoxide hydrolase inhibitor, the microsomal incubations converted (1-chloroethenyl)oxirane to 3-chlorobut-3-ene-1,2-diol (21a/21b). When microsomal incubations were supplemented with glutathione, 1-hydroxybut-3-en-2-one was not detected because of its rapid conjugation with this thiol scavenger.
- Cottrell,Golding,Munter,Watson
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p. 1552 - 1562
(2007/10/03)
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- A New Platinum Complex Catalyzed Reaction Involving Nucleophilic Substitution at the Central Carbon Atom of the π-Allyl Ligand
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The reaction of 2-chloro-allyl acetate with sodium ethyl acetoacetate in the presence of a platinum-(0) complex gave furan derivatives. The key feature of this new platinum-catalyzed reaction is the nucleophilic substitution at the central carbon atom of π-allyl complexes. The regioselectivity of the nucleophilic attacks (central or terminal) is dependent on the pKa of the nucleophile. In addition, a labeling experiment revealed that a rapid syn-anti isomerization of the (π-allyl) platinum complexes occurs.
- Kadota, Joji,Komori, Shinji,Fukumoto, Yoshiya,Murai, Shinji
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p. 7523 - 7527
(2007/10/03)
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- Reaction of Benzeneseleninyl Chloride with Olefins in the Presence of a Lewis Acid. A Novel One Step Vinylic Chlorination
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In the presence of aluminum chloride benzeneseleninyl chloride was found to be an exellent vinylic chlorinating reagent of olefins under mild conditions.However, such olefins as styrene, trans-stilbene, and trans-1-phenylpropene afforded dichloro adducts under similar conditions.A plausible reaction mechanism involving positive chlorine intermediate is proposed.
- Kamigata, Nobumasa,Satoh, Takeshi,Yoshida, Masato
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p. 449 - 454
(2007/10/02)
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