Novel Synthesis of 1-Cyanocyclopropane-1-carboxylic Acid and Its Application to the Synthesis of Amino Acids Containing Cyclopropane Rings

Ohno, Masahiro; Tanaka, Haruhisa; Komatsu, Mitsuo; Ohshiro, Yoshiki

doi:10.1055/s-1991-20923

Cited by 39 publications

(8 citation statements)

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“…The success in developing an updated method for synthesizing [ 11 C]3 triggered our interest in exploring carbon nucleophiles, generated in situ via FMDS approach, for 11 C-carboxylation. Although FMDS method had been used to generate a variety of nucleophiles in many organic reactions (such as alkylation, allylation, alkynylation, arylation, vinylation, and cyanation), and had been broadly used to synthesize complex molecules 11 , there are only a handful of reports of directly using organosilanes for carboxylation reaction without involving any transition metal catalysts [19][20][21][22][23][24][25][26][27][28][29] . While organometallic reagent catalyzed carboxylation has already drawn extensive attention to radiochemistry research [30][31][32] , to the best of our knowledge, we have not found any reports of the use of the FMDS methodology for direct 11 Ccarboxylation.…”

Section: Synthesis Of [ 11 C]acetoacetic Acid Via Fmds 11 C-carboxylamentioning

confidence: 99%

A general 11C-labeling approach enabled by fluoride-mediated desilylation of organosilanes

Qü

Babich

et al. 2020

Nat Commun

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Carbon-11 (11C) is one of the most ideal positron emitters for labeling bioactive molecules for molecular imaging studies. The lack of convenient and fast incorporation methods to introduce 11C into organic molecules often hampers the use of this radioisotope. Here, a fluoride-mediated desilylation (FMDS) 11C-labeling approach is reported. This method relies on thermodynamically favored Si-F bond formation to generate a carbanion, therefore enabling the highly efficient and speedy incorporation of [11C]CO2 and [11C]CH3I into molecules with diversified structures. It provides facile and rapid access to 11C-labeled compounds with carbon-11 attached at various hybridized carbons as well as oxygen, sulfur and nitrogen atoms with broad functional group tolerance. The exemplified syntheses of several biologically and clinically important radiotracers illustrates the potentials of this methodology.

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Section: Synthesis Of [ 11 C]acetoacetic Acid Via Fmds 11 C-carboxylamentioning

confidence: 99%

A general 11C-labeling approach enabled by fluoride-mediated desilylation of organosilanes

Qü

Babich

et al. 2020

Nat Commun

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“…This did not prove to be the case for switching the relative orientation of the 1-ethyl-propyl group of 12 , as the isomer 54 was found to have similar potency to 12 . Noteworthy is the fact that unsubstituted 1-aminomethylcyclopropane carboxylic acid 55 did not bind to α 2 -δ or system L, and as a point of reference, pregabalin 1 demonstrated 0.019 μM binding affinity to α 2 -δ ( K i ) and 158 μM to system L (IC 50 ) as a single enantiomer.…”

Section: Pharmacologymentioning

confidence: 99%

Novel Cyclopropyl β-Amino Acid Analogues of Pregabalin and Gabapentin That Target the α₂-δ Protein

et al. 2005

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As part of a program aimed at generating compounds with affinity for the alpha(2)-delta subunit of voltage-gated calcium channels, several novel beta-amino acids were prepared using an efficient nitroalkane-mediated cyclopropanation as a key step. Depending on the ester that was chosen, the target amino acids could be prepared in as few as three steps. The cyclopropyl amino acids derived from ketones proved to be potent binders of the alpha(2)-delta subunit of voltage-gated calcium channels, but did not interact with the large neutral amino acid system L (leucine) transporter. Anticonvulsant effects were observed in vivo with compound 34 but only after intracerebroventricular (icv) administration, presumably due to inadequate brain concentrations of the drug being achieved following oral dosing. However, pregabalin 1 was active in the DBA/2 model after oral (and icv) dosing, supporting a hypothesis that active transport is a prerequisite for such zwitterionic species to cross the blood-brain barrier.

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“…15 When treated with a source of fluoride, it may create a nucleophile that can react in high yield with proton sources, 16 alkyl iodides and triflates, 17 aldehydes, 18 and ketones, 19 as well as acylating groups such as acid chlorides 20 and carbon dioxide. 21 The unstable photoadducts were elaborated to more stable compounds in order to properly characterize them and, in particular, to verify the cis-syn-cis-relationship of the rings that should arise as a result of the endo selectivity (Scheme 4). The regio-and stereospecific addition of free radicals to the top face of the vinyl cyclopropanes formed in the reaction was used to add substituted thiophenols to the exo face of the vinylcyclopropane, at first following a protocol 9 in refluxing acetonitrile with benzoyl peroxide, then in a 'green' fashion of solventless reaction in air at room temperature with 1-2.2 equivalents of the neat thiophenol.…”

Section: Scheme 2 Reaction Progress Results In the Formation Of An Ismentioning

confidence: 99%

β-Silyl Arenes in the Arene-Olefin Photocyclization Reaction

deLong¹,

Mathews²,

Cohen³

et al. 2007

Synthesis

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The 'b-silyl effect' of ground-state chemistry has been found to be operative in excited-state systems as well, where it exerts just as remarkable of an effect on the yields and selectivity of the intermolecular arene-olefin photocyclization reaction. Benzyltrimethylsilane has been found to undergo intermolecular areneolefin photocyclization with alicyclic hydrocarbon alkenes to provide 2,6-meta-adducts with yields of 65-90% in a regio-and stereoselective manner. Particularly encouraging are the reactions with cyclohexene and with cis-cyclooctene, as both of these substrates give anomalous results with many arenes, but fall perfectly in line when coupling with benzyltrimethylsilane. These data augur well for the use of b-silyl directing groups in more complex photocyclization reactions. The ability of a C-Si sp 3 bond to stabilize an incipient positive charge in the b-position by hyperconjugation apparently also allows it to stabilize a transiently electron-deficient excited state, in the same way that an electron-donating group (e.g., a methyl or a methoxy group) has been observed to direct the regiochemistry of the arene-olefin photocyclization reaction. To fully characterize the photoadducts, they have been elaborated via radical addition of substituted thiophenols to crystalline compounds and Xray crystal structures obtained.

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Novel Synthesis of 1-Cyanocyclopropane-1-carboxylic Acid and Its Application to the Synthesis of Amino Acids Containing Cyclopropane Rings

Cited by 39 publications

References 0 publications

A general 11C-labeling approach enabled by fluoride-mediated desilylation of organosilanes

A general 11C-labeling approach enabled by fluoride-mediated desilylation of organosilanes

Novel Cyclopropyl β-Amino Acid Analogues of Pregabalin and Gabapentin That Target the α₂-δ Protein

β-Silyl Arenes in the Arene-Olefin Photocyclization Reaction

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Novel Synthesis of 1-Cyanocyclopropane-1-carboxylic Acid and Its Application to the Synthesis of Amino Acids Containing Cyclopropane Rings

Cited by 39 publications

References 0 publications

A general 11C-labeling approach enabled by fluoride-mediated desilylation of organosilanes

A general 11C-labeling approach enabled by fluoride-mediated desilylation of organosilanes

Novel Cyclopropyl β-Amino Acid Analogues of Pregabalin and Gabapentin That Target the α2-δ Protein

β-Silyl Arenes in the Arene-Olefin Photocyclization Reaction

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Novel Cyclopropyl β-Amino Acid Analogues of Pregabalin and Gabapentin That Target the α₂-δ Protein