Synthesis of Fluorogypsetin and Fluorobrevianamide E by a Novel Fluorination-Cyclization ofcyclo-L-Trp-L-AAs

Shibata, Norio; Tarui, Takanao; Doi, Yasuhiro; Kirk, Kenneth L.

doi:10.1002/1521-3757(20011203)113:23<4593::aid-ange4593>3.0.co;2-8

Cited by 39 publications

(32 citation statements)

References 33 publications

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“…Subsequent deprotonation leads to the unsatu rated product or incorporation of the solvent leads to Rittertype products ( FiguRe 23). Shibata et al applied a fluorination-cycliza tion protocol to the synthesis of more function alized fluorinated analogues of two biologically active molecules, gypsetin and brevianamide E [32]. They envisaged a process featuring fluorination at the 3position of a substituted indole followed by cyclization upon nucleo philic attack at the 2position by a tethered nucleophile.…”

Section: Fluorocyclizations Featuring An Electrophilic Fluorinationmentioning

confidence: 99%

Developments in Fluorocyclization Methodologies

2009

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Fluorinated organic compounds constitute a significant proportion of medicines marketed today. Since heterocycles are submotifs frequently encountered in lead compounds, the corresponding fluorinated molecules that possess coupling functional groups to increase structural complexity are sought-after building blocks, especially those with stereogenic elements. To access fluoro-heterocycles, fluorocyclizations constitute an important category of reactions that permit multiple bond construction in one pot. Reactions featuring both nucleophilic and electrophilic sources of fluorine have proved valuable for the delivery of fluorinated carbo- and heterocycles. Mechanistically, two scenarios have been validated with the fluorination occurring either prior to or after the cyclization event. Fluorinated biologically active molecules prepared by employing a fluorocyclization protocol are rare, with two notable exceptions being the synthesis of fluorogypsetin and fluorobrevianamide E. Various levels of diastereocontrol were obtained with best results observed when the cyclization step precedes the fluorination. To date, asymmetric fluorocyclizations have not been explored, with the exception of a Nazarov fluorination process. In essence, this process features a catalytic asymmetric cyclization followed by a diastereoselective fluorination. Asymmetric fluoroheterocyclizations are, however, not known. For this methodology to serve medicinal chemistry, conceptual advances are essential to access fluorinated pharmacophores with programmable stereocontrol as and when necessary.

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Section: Fluorocyclizations Featuring An Electrophilic Fluorinationmentioning

confidence: 99%

Developments in Fluorocyclization Methodologies

2009

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“…This indole moiety is present in a wide variety of natural products, including gypsetin [45,46] and brevianamide E. [47] The synthesis of the fluorinated core of these biologically relevant molecules by using 1 is illustrated in Schemes 16 and 17). [48] Scheme 14. The conformation and configuration at the anomeric center of the intermediates determine the anomeric selectivity in reactions of glycals.…”

Section: Electrophilic Fluorination Of Indolesmentioning

confidence: 99%

“…[52] Scheme 17. Synthesis of the fluorinated core of brevianamide E. [48] Electrophilic Fluorination Angewandte Chemie…”

Section: Electrophilic Fluorination Of Indolesmentioning

confidence: 99%

Selectfluor: Mechanistic Insight and Applications

et al. 2004

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The replacement of hydrogen atoms with fluorine substituents in organic substrates is of great interest in synthetic chemistry because of the strong electronegativity of fluorine and relatively small steric footprint of fluorine atoms. Many sources of nucleophilic fluorine are available for the derivatization of organic molecules under acidic, basic, and neutral conditions. However, electrophilic fluorination has historically required molecular fluorine, whose notorious toxicity and explosive tendencies limit its application in research. The necessity for an electrophilic fluorination reagent that is safe, stable, highly reactive, and amenable to industrial production as an alternative to very hazardous molecular fluorine was the inspiration for the discovery of selectfluor. This reagent is not only one of the most reactive electrophilic fluorinating reagents available, but it is also safe, nontoxic, and easy to handle. In this Review we document the many applications of selectfluor and discuss possible mechanistic pathways for its reaction.

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“…Because the oxindole ling is widely found among natural products, the development of a general method for catalytic asymmetric fluorination reaction of oxindoles would be useful in the field of medicinal chemistry. 27 At the outset, we examined the reaction of the non-protected 3-phenyl-substituted oxindole 22a using a catalytic amount of 5c as a catalyst (Table 5). Unfortunately, however, the reaction with NFSI was slow, and negligible asymmetric induction was observed (entry 1).…”

Section: Fluorination Of N-boc Oxindoles26mentioning

confidence: 99%

Catalytic Enantioselective .ALPHA.-Fluorination of Carbonyl Compounds Using Chiral Transition Metal Complexes

Hamashima

Sodeoka

2007

J. Syn. Org. Chem., Jpn.

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: Two catalytic systems were developed for efficient catalytic enantioselective a-fluorination reactions of carbonyl compounds. Cationic Pd complexes were found to be effective for fluorination of active methine and methylene compounds, and various substrates including B-ketoesters, B-ketophosphonates, and other related compounds were fluorinated in environmentally friendly alcoholic solvents (up to 99% ee). This system was also applicable to the reaction of 3-substituted oxindole derivatives. In addition, we succeeded in developing a novel trinary system NiCl2-binap/R3SiOTf/2,6-lutidine for the reaction of less acidic a-aryl acetic acid derivatives, and the desired reaction proceeded smoothly to give the corresponding monofluorinated compounds in a highly enantioselective manner (up to 88% ee). Our fluorination reactions are versatile, being applicable to stereoselective synthesis of chiral fluorinated analogues of fundamental building blocks and catalytic asymmetric synthesis of BMS204352, a promising agent for the treatment of stroke.

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Synthesis of Fluorogypsetin and Fluorobrevianamide E by a Novel Fluorination-Cyclization ofcyclo-L-Trp-L-AAs

Cited by 39 publications

References 33 publications

Developments in Fluorocyclization Methodologies

Developments in Fluorocyclization Methodologies

Selectfluor: Mechanistic Insight and Applications

Catalytic Enantioselective .ALPHA.-Fluorination of Carbonyl Compounds Using Chiral Transition Metal Complexes

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