Stereoselective substitution of flavan skeletons: synthesis of dryopteric acid

Ohmori, Ken; Ushimaru, Naoko; Suzuki, Keisuke

doi:10.1016/s0040-4039(02)01826-9

Cited by 19 publications

(18 citation statements)

References 14 publications

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“…We now turned our attention to the cross coupling of acetate 3 and sulfide 4 (15). It was found that selective activation of acetate 3 was quite facile (Scheme 5, table).…”

Section: Resultsmentioning

confidence: 99%

“…Regio- selective installation of a bromine atom was easily achieved by treatment of 3 with N-bromosuccinimide in CH 2 Cl 2 (22), giving the requisite C(8)-bromide 12 in 95% yield (Scheme 6). Moreover, the corresponding phenylthio derivative 13 was obtained in a high ␤-selectivity (␣͞␤ ϭ 5:95) by treatment of 12 with PhSH in the presence of BF 3 ⅐OEt 2 in 91% yield (15).…”

Section: Resultsmentioning

confidence: 99%

“…Our basis for innovation was the ''sugar-flavonoid analogy'' inferred by the S N 1 reactivity shared by carbohydrates and polyphenols ( Fig. 2) (14)(15)(16). Because the S N 1 reactivity of anomeric position of sugars is primarily governed by the endocyclic oxygen atom, the corresponding reactivity of the C(4) position of polyphenols is further facilitated by the three oxygen substituents.…”

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confidence: 99%

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Oligomeric catechins: An enabling synthetic strategy by orthogonal activation and C(8) protection

Ohmori

Ushimaru

Suzuki

2004

Proc. Natl. Acad. Sci. U.S.A.

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Controlled formation of oligomeric catechins has become possible by an orthogonal synthetic strategy. Bromo-capping of the C(8) position of the flavan skeleton enabled the equimolar coupling of electrophilic and nucleophilic catechin derivatives, enabling an efficient synthetic strategy to complex catechin oligomers.A lthough natural polyphenols have long played a part in human life as ingredients of wine, tea, or herbal medicines (1-3), it was only recently that their biological functions have been unveiled at the molecular level. The realization that specific interactions of polyphenols with biomolecules, such as proteins (4), exert powerful biological activities has stimulated the search for new pharmaceutical entities derived from polyphenolic entities. These investigations, however, are often hampered by the difficulty in isolating the requisite compounds in pure and structurally defined form, largely because their procurement has relied on natural sources, e.g., plant extracts. Unfortunately, these sources generally produce mixture of closely related compounds, not readily separable even with the aid of modern chromatographic and analytical methods. The difficulty in securing pure samples of these materials, coupled with their promising and powerful biological activities, collude to offer an enticing challenge to organic synthesis for supplying valuable, homogeneous samples for biological testing.Among the polyphenol classes that have attracted recent interest are the condensed tannins (procyanidins), which have been identified as antiviral, antibacterial, and antitumor agents. These bioactive oligomeric structures, which occur in popular delicacies such as cocoa-derived products, have captured the interest of chemists and connoisseurs alike for their potential biological activities (5-7). These exciting properties have inspired synthetic efforts aimed at producing and characterizing these challenging molecules and elucidating their biological mode of action. Noteworthy are the elegant contributions by Kozikowski, Tückmantel, and coworkers (7-10), who have shown the potential biological activities of higher epicatechin oligomers prepared by nonselective oligomerization and separation.Further progress in this area is hampered by the need for reliable synthetic methods capable of providing any oligomeric polyphenol with rigorous control of stereo-and regiochemistry and the degree of oligomerization. The synthetic challenge posed by such oligomeric catechins can be clearly seen in the target structures (Fig. 1). Homooligomers, such as 1, containing a single repeating unit, present a formidable but not insurmountable synthetic challenge. In contrast, heterooligomers such as 2, containing several units distinct in stereochemistry and the oxidation pattern, demand innovative synthetic solutions. Furthermore, these structures will be accessible only through efficient step-by-step (iterative) couplings, rather than uncontrolled polymerization.This central problem is evident already in dimer formation illustrated i...

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“…We now turned our attention to the cross coupling of acetate 3 and sulfide 4 (15). It was found that selective activation of acetate 3 was quite facile (Scheme 5, table).…”

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

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Oligomeric catechins: An enabling synthetic strategy by orthogonal activation and C(8) protection

Ohmori

Ushimaru

Suzuki

2004

Proc. Natl. Acad. Sci. U.S.A.

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“…In addressing this point, we initiated our study with the stereoselective substitution at the C(4)‐position of the flavan skeleton, invoking a concept based on glycosidation chemistry (Figure 3). 4 We prepared the C(4)‐acetoxylated catechin/epicatechin derivatives, 1 and 2 , as a “flavanyl donor” instead of a glycosyl donor, which were treated with various nucleophiles in the presence of a Lewis acid, e.g. BF 3 ·OEt 2 .…”

Section: The C(4)‐elaboration Of Flavan Skeleton Based On the “Flavonmentioning

confidence: 99%

“…The method was applicable not only for various carbon nucleophiles, such as ketene silyl acetal, allylmetal, 1,3,5‐trialkoxy benzenes, and indoles, but also for heteroatom nucleophiles, e.g. Me 3 SiN 3 and PhSH, providing an access to the corresponding substituted product 4a. Further utility of this method was demonstrated by natural product syntheses, targeted dryopteric acid (flavan–acetate hybrid)4a and lotthanongine (flavan–indole hybrid) 4c…”

Section: The C(4)‐elaboration Of Flavan Skeleton Based On the “Flavonmentioning

confidence: 99%

Synthetic challenge to ubiquitous natural products from plant origin: flavan‐derived polyphenols

Ohmori

2011

The Chemical Record

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Flavan-derived polyphenols (catechin derivatives), widely destributed in the plant kingdom, have been given much considerable attention owing to their significant bioactivitites coupled with their extreme structural diversity. However, biochemical functions of this class of molecules are still not well understood because of the limited availavility of natural samples in sufficient quantity and quality. Here we report our synthetic challenges toward flavan-derived polyphenols, based on the flavonoid-sugar analogy. The key for success was the C(4)-elaboration of the flavan skeleton, which posed an important relevance to their structure diversification both in terms of the biogenetic origin of flavan derivatives as well as chemical synthesis of this class of compounds. Various nucleophilic units could be introduced to the C(4) position via the S(N) 1-type substitution, and orthogonal activation of two distinct flavan units enabled block assembly of linear catechin oligomers. These methodologies would serve as a reliable way to supply valuable, homogeneuous samples for biological testing.

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Real‐Time Analysis of Polyphenol–Protein Interactions by Surface Plasmon Resonance Using Surface‐Bound Polyphenols

López

Tran

Viault

et al. 2021

Chemistry A European J

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As election of bioactive polyphenols of different structural classes, such as the ellagitannins vescalagin and vescalin, the flavanoidsc atechin, epicatechin,e pigallocatechin gallate (EGCG), and procyanidin B2, and the stilbenoids resveratrol and piceatannol, were chemically modified to bear ab iotin unit for enabling their immobilization on streptavidin-coateds ensor chips. These sensorc hips were used to evaluate in real time by surfacep lasmon resonance(SPR) the interactionso fthree different surface-bound polyphenolic ligandsp er sensorc hip with variousp rotein analytes, including human DNA topoisomerase IIa,f lavonoid leucoanthocyanidin dioxygenase, B-cell lymphoma 2a poptosis regulator protein,a nd bovine serum albumin. The types and levels of SPR responses unveiled major differences in the association,o rl ack thereof,a nd dissociation between ag iven protein analyte and different polyphenolic ligands. Thus,t his multi-analysis SPR technique is av aluablem ethodology to rapidly screena nd qualitatively compare various polyphenol-protein interactions.

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Stereoselective substitution of flavan skeletons: synthesis of dryopteric acid

Cited by 19 publications

References 14 publications

Oligomeric catechins: An enabling synthetic strategy by orthogonal activation and C(8) protection

Oligomeric catechins: An enabling synthetic strategy by orthogonal activation and C(8) protection

Synthetic challenge to ubiquitous natural products from plant origin: flavan‐derived polyphenols

Real‐Time Analysis of Polyphenol–Protein Interactions by Surface Plasmon Resonance Using Surface‐Bound Polyphenols

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