Stereoselective and Efficient Total Synthesis of Optically Active Tetrodotoxin from <scp>d</scp>-Glucose

Sato, Kenichi; Akai, Shoji; Shoji, Hirotsugu; Sugita, Naoki; Yoshida, Shiho; Nagai, Yoshinao; Suzuki, Katsuhiko; Nakamura, Yutaka; Kajihara, Yasuhiro; Funabashi, Masuo; Yoshimura, Juji

doi:10.1021/jo701655v

Cited by 84 publications

(55 citation statements)

References 43 publications

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“…[39] Nitrocyclohexane derivative 53 obtained from d-glucose has been envisaged as ak ey intermediatei nt he total synthesis of the marine toxint etrodotoxin (Scheme 17). [40] Then itronate anion of compound 53 was thus converted into polyhydroxylated cyclohexanone 54 by reaction with ozonea tÀ78 8 8Cw ith complete retention of the original configuration of the existing stereocenters. [41] Ap rocedure for the synthesis of opticallya ctive bamino-a-hydroxy acid 58 employs as starting material lactol 55 obtained in few steps from l-phenylalanine (Scheme 18).…”

Section: O Xidative Methodsmentioning

confidence: 99%

The Nitro to Carbonyl Conversion (Nef Reaction): New Perspectives for a Classical Transformation

2015

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This review article reports new procedures and practical application of the nitro to carbonyl conversion that appeared in the literature after our\ud comprehensive report published in 2004. Beside traditional and well explored reactant systems, new procedures including the utilization of molecular oxygen and photoredox catalysis have been introduced for the Nef reaction. Of notable interest is the utilizationof the nitro to carbonyl conversion in tandem and cascade processes aimed at the preparation of hetero and carbocyclic derivatives

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Section: O Xidative Methodsmentioning

confidence: 99%

The Nitro to Carbonyl Conversion (Nef Reaction): New Perspectives for a Classical Transformation

2015

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“…Experiments with: 1) these congeners as well as possible synthetic derivatives of both STX and TTX (good progress in guanidinium alkaloid syntheses is promising in this regard; Andresen and Du Bois 2009; Mulcahy and Du Bois 2008;Nishikawa et al 2004;Sato et al 2008); 2) close relatives of KIIIA, such as the -conotoxins SIIIA and SmIIIA (Bulaj et al 2005;West et al 2002); and 3) mutants of the channel, such as Na V 1.2[F385C] ), should advance our understanding of the mechanism of action of guanidinium alkaloids and -conopeptides that target site 1 of VGSCs. Furthermore, if active, covalently linked alkaloid-peptide adducts can be synthesized, these should provide insights into the arrangement of the units when bound to site 1, as well as also serve as second-generation ligands for sodium channels.…”

Section: Structural Models Of Alkaloid and Peptide Docked At The Outementioning

confidence: 99%

Cooccupancy of the Outer Vestibule of Voltage-Gated Sodium Channels by μ-Conotoxin KIIIA and Saxitoxin or Tetrodotoxin

Zhang¹,

Gruszczyński

Walewska³

et al. 2010

Journal of Neurophysiology

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of the outer vestibule of voltage-gated sodium channels by -conotoxin KIIIA and saxitoxin or tetrodotoxin. J Neurophysiol 104: 88 -97, 2010. First published April 2, 2010 doi:10.1152/jn.00145.2010. The guanidinium alkaloids tetrodotoxin (TTX) and saxitoxin (STX) are classic ligands of voltage-gated sodium channels (VGSCs). Like TTX and STX, -conotoxin peptides are pore blockers but with greater VGSC subtype selectivity. -Conotoxin KIIIA blocks the neuronal subtype Na V 1.2 with nanomolar affinity and we recently discovered that KIIIA and its mutant with one fewer positive charge, KIIIA[K7A], could act synergistically with TTX in a ternary peptide·TTX·Na V complex. In the complex, the peptide appeared to trap TTX in its normal binding site such that TTX could not readily dissociate from the channel until the peptide had done so; in turn, the presence of TTX accelerated the rate at which peptide dissociated from the channel. In the present study we examined the inhibition of Na V 1.2, exogenously expressed in Xenopus oocytes, by STX (a divalent cation) and its sulfated congener GTX2/3 (with a net ϩ1 charge). Each could form a ternary complex with KIIIA and Na V 1.2, as previously found with TTX (a monovalent cation), but only when STX or GTX2/3 was added before KIIIA. The KIIIA·alkaloid·Na V complex was considerably less stable with STX than with either GTX2/3 or TTX. In contrast, ternary KIIIA[K7A]·alkaloid·Na V complexes could be formed with either order of ligand addition and were about equally stable with STX, GTX2/3, or TTX. The most parsimonious interpretation of the overall results is that the alkaloid and peptide are closely apposed in the ternary complex. The demonstration that two interacting ligands ("syntoxins") occupy adjacent sites raises the possibility of evolving a much more sophisticated neuropharmacology of VGSCs. I N T R O D U C T I O NVoltage-gated sodium channels (VGSCs) are responsible for the upstroke of action potentials in excitable cells. Tetrodotoxin (TTX) and saxitoxin (STX) are guanidinium alkaloids (Fig. 1A) that block six of the nine isoforms of the pore-bearing ␣-subunit of mammalian VGSCs with K d values in the nanomolar range (Catterall et al. 2005). -Conotoxins, which also block VGSCs, are peptides of 16 to 25 residues, including six cysteines that form a characteristic disulfide framework (see Fig. 1B) (Terlau and Olivera 2004). In contrast to the promiscuity of TTX and STX, GIIIA, the best-studied -conotoxin, is significantly more potent against the skeletal muscle subtype of channel Na V 1.4 (half-maximal inhibitory concentration [IC 50 ] ϭ 19 nM), than other TTX-sensitive subtypes, such as brain We recently discovered -conotoxins KIIIA and SIIIA, which block Na V 1.2 with higher affinity than Na V 1.4 (Bulaj et al. 2005;Yao et al. 2008;Zhang et al. 2007). Single-channel analyses of brain VGSCs in planar lipid bilayers showed that KIIIA produced only a partial block (Zhang et al. 2007). In saturating concentrations of KIIIA or its mutant KIIIA[K7A], a residual sodium curre...

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“…Glutamic acid an aminoacid that had been identified on cocoa fermentation with a concentration of 7.4 (0 hrs) and 11.7 (72 hrs) (De Brito et al, 2001). D-(+)-Glucuronic acid γ-lactone wich has been on the synthesis of optically active glucopyranoses (Sato et al, 2008) and long-chain alkyl glucofuranosides (Raaijmakers et al, 1994). Xilitol is a sugar that is nonfermentable to alcohol and present interesting properties such as antidiabetic, antioxidant and anticarcinogenicity (Venkateswar et al, 2016).…”

Section: Resultsmentioning

confidence: 99%

Physicochemical characterization of Theobroma cacao L. mucilage, in Ecuadorian coast

Balladares¹,

García²,

Chóez-Guaranda³

et al. 2016

Emir. J. Food Agric

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Stereoselective and Efficient Total Synthesis of Optically Active Tetrodotoxin from d-Glucose

Cited by 84 publications

References 43 publications

The Nitro to Carbonyl Conversion (Nef Reaction): New Perspectives for a Classical Transformation

The Nitro to Carbonyl Conversion (Nef Reaction): New Perspectives for a Classical Transformation

Cooccupancy of the Outer Vestibule of Voltage-Gated Sodium Channels by μ-Conotoxin KIIIA and Saxitoxin or Tetrodotoxin

Physicochemical characterization of Theobroma cacao L. mucilage, in Ecuadorian coast

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