Synthesis of Both Enantiomers of Flavanone and 2-Methylchromanone

Noda, Yoshifumi; Watanabe, Morio

doi:10.1002/1522-2675(200210)85:10<3473::aid-hlca3473>3.0.co;2-7

Cited by 24 publications

(13 citation statements)

References 6 publications

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“…In addition, flavanones containing electron-donating substituents (alkoxy or hydroxy) in the C4´ position are particularly susceptible to racemization 7,11. A limited number of approaches for the stereoselective synthesis of flavanones have been developed, including Mitsunobu reactions of chiral alcohols, acylation reactions of chiral ethers, and conjugate additions of aryl substituents to chromenes 12–16. However, these approaches are not general and would not provide the abyssinone core in a concise manner.…”

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confidence: 99%

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Concise Syntheses of the Abyssinones and Discovery of New Inhibitors of Prostate Cancer and MMP-2 Expression

Farmer

Biddle

Nibbs

et al. 2010

ACS Med. Chem. Lett.

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Hydrogen-bonding catalysis is an emerging field that facilitates rapid access to medicinally relevant enantioenriched small molecules. Here, we report the first asymmetric total syntheses of four members of the abyssinone class of natural products (I, II, III, and IV 4´-OMe) via quinine- or quinidine-derived thiourea-catalyzed intramolecular conjugate additions of β-keto ester alkylidenes. This concise strategy includes a tandem deprotection/decarboxylation final step that delivers all four natural products and their corresponding antipodes. A preliminary evaluation of all of these small molecules against a metastatic human prostate cancer cell line has identified that these compounds selectively and differentially inhibit cell growth and downregulate the expression of matrix metalloproteinase-2 (MMP-2) at non-toxic concentrations.

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confidence: 99%

“…The requisite allyl-protected alkylidenes 10–13 were synthesized directly from the corresponding aldehydes using our mild bis-aminal approach 16. These substrates set the stage for the decarboxylation and phenol deprotection to be performed in one flask to deliver the target molecules 21.…”

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confidence: 99%

Concise Syntheses of the Abyssinones and Discovery of New Inhibitors of Prostate Cancer and MMP-2 Expression

Farmer

Biddle

Nibbs

et al. 2010

ACS Med. Chem. Lett.

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“…Until Noda and Watanabe’s report on the synthesis of flavanone and 2-methylchromanone, [62] there had only been five reports of syntheses of enantio-enriched flavanones and 2-methylchromanones. [35b,36,38,46,58] In their synthesis, Noda and Watanabe generated dithiane 59 , which was lithiated with n BuLi and added to either ( S )- or ( R )-styrene oxide to generate diol 60 (Scheme 28).…”

Section: Carbon–heteroatom Bond Formationmentioning

confidence: 99%

“…[35b,36,38,46,58] In their synthesis, Noda and Watanabe generated dithiane 59 , which was lithiated with n BuLi and added to either ( S )- or ( R )-styrene oxide to generate diol 60 (Scheme 28). [62] Finally, Mitsunobu inversion and desulfurization generated the enantio-enriched flavanone. By treatment of dithiane 59 with either enantiomer of styrene oxide or propylene oxide, both flavanone ( 5 ) and 2-methylchromanone ( 16 ) could be accessed with high levels of enantiomeric excess.…”

Section: Carbon–heteroatom Bond Formationmentioning

confidence: 99%

Asymmetric Methods for the Synthesis of Flavanones, Chromanones, and Azaflavanones

2011

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Flavanones, chromanones, and related structures are privileged natural products that display a wide variety of biological activities. Although flavanoids are abundant in nature, there are a limited number of available general and efficient synthetic methods for accessing molecules of this class in a stereoselective manner. Their structurally simple architectures belie the difficulties involved in installation and maintenance of the stereogenic configuration at the C2 position, which can be sensitive and can undergo epimerization under mildly acidic, basic, and thermal reaction conditions. This review presents the methods currently used to access these related structures. The synthetic methods include manipulation of the flavone/flavanone core, carbon-carbon bond formation, and carbon–heteroatom bond formation.

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“…Both enantiomers of 1a and 2a were prepared via the ring-opening reaction of chiral epoxides with a dithiane anion, followed by the intramolecular Mitsunobu reaction. 7 Hodgetts described two approaches to (S)-1a and (R)-2a. 8 One of the approaches utilized the oxidation of the preformed chiral 2-substituted chromans and another approach involved the intramolecular Mitsunobu reaction.…”

Section: Introductionmentioning

confidence: 99%