Enantioselective synthesis of the AB ring fragment of gambiertoxin 4B. Implication for the absolute configuration of gambiertoxin 4B and ciguatoxin

Suzuki, Toshio; Sato, Ohki; Hirama, Masahiro; Yamamoto, Yoshinori; Murata, Michio; Yasumoto, Takeshi; Harada, Nobuyuki

doi:10.1016/0040-4039(91)80025-2

Cited by 52 publications

(21 citation statements)

References 7 publications

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“…4–6,8,10–12) The synthetic CTX3C was determined to be identical to the naturally occurring form in every respect, including mouse acute toxicity, which unambiguously confirmed the absolute stereochemistry of ciguatoxins. 28,32,33) Thus, the power of our unified convergent [X + 2 + Y] coupling strategy 12,40) for constructing this large and complex ladder-like polyether system was clearly demonstrated. In addition, it should be noted that the synthetic fragments and penultimate intermediate, tris-benzyl ether 46 , did not exhibit detectable toxicity (see Fig.…”

Section: Determination Of the Absolute Configuration Of Ciguatoxins Amentioning

confidence: 82%

“…Early on, we developed enantioselective routes to the medium (7-, 8-, and 9-membered) ring ethers of ciguatoxins 27–31) and the circular dichroism (CD) studies of synthetic AB ring fragments implicated the absolute configuration of CTXs. 28,32,33) Then, we quickly realized that convergent assembly of the structural fragments was the key for successful construction of the huge ladder-like polycyclic ether system. 12,34) …”

Section: Determination Of the Absolute Configuration Of Ciguatoxins Amentioning

confidence: 99%

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Total synthesis and related studies of large, strained, and bioactive natural products

Hirama

2016

Proceedings of the Japan Academy. Ser. B: Physical and Biologic

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Our chemical syntheses and related scientific investigations of natural products with complex architectures and powerful biological activities are described, focusing on the very large 3 nm-long polycyclic ethers called the ciguatoxins, highly strained and labile chromoprotein antitumor antibiotics featuring nine-membered enediyne cores, and extremely potent anthelmintic macrolides called the avermectins.

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Section: Determination Of the Absolute Configuration Of Ciguatoxins Amentioning

confidence: 82%

Section: Determination Of the Absolute Configuration Of Ciguatoxins Amentioning

confidence: 99%

Total synthesis and related studies of large, strained, and bioactive natural products

Hirama

2016

Proceedings of the Japan Academy. Ser. B: Physical and Biologic

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“…Pd-catalyzed allylic substitutions involving silyl ethers as pronuclecophiles have precedence in the literature. [51,52] However, such reactions normally involve the presence of nucleophiles such as fluorides or chlorides which induce desilylation, leading to an alkoxide which is the actual nucleophile in the allylation reaction. In the present case, ethoxide liberated from the allyl carbonate might be the nucleophile responsible for desilylation.…”

Section: Resultsmentioning

confidence: 99%

Palladium‐Catalyzed O‐Allylation of α‐Hydroxy Carbonyl Compounds

Schmidt

Nave

2006

Adv Synth Catal

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“…Based on a comparison of their CD spectra, 5R configuration was proposed for CTX4B (2). 17 However, uncertainty remained due to the small Cotton effects observed.…”

Section: Elucidation Of the C2 Configuration Of Ciguatoxinmentioning

confidence: 99%

Bioorganic Studies Utilizing Rationally Designed Synthetic Molecules: Absolute Configuration of Ciguatoxin and Development of Immunoassay Systems

Oguri¹

2007

Bulletin of the Chemical Society of Japan

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Ciguatoxins are the major causative toxins in ciguatera seafood poisoning. The limited availability of ciguatoxins has precluded structural elucidation and development of a reliable and specific immunoassay for detecting the toxins in contaminated fish. To seek a solution for the longstanding problem of ciguatera, we addressed the synthetic challenge by utilizing rationally designed model compounds of ciguatoxins. The C2 configuration and entire absolute configuration of ciguatoxin were successfully elucidated with minutest amounts of natural toxins, using an approach which combined partial structure synthesis, microscale chemical transformations, and the CD exciton chirality method. On the basis of the absolute configuration, the partial structures of ciguatoxins were designed and synthesized as haptens for the preparation of anti-ciguatoxin antibodies. Monoclonal antibodies (mAbs) against both ends of ciguatoxin CTX3C were prepared by immunization of mice with protein conjugates of synthetic haptens of the ABCDE-ring and the IJKLM-ring, in place of the natural toxin. Haptenic groups with surface areas larger than 400 Å 2 were required to produce mAbs, which could bind strongly to CTX3C itself. A direct sandwich enzyme-linked immunosorbent assay (ELISA) using these mAbs was shown to detect CTX3C at the ppb level with no cross-reactivity against other related marine toxins, including brevetoxin A, brevetoxin B, okadaic acid, or maitotoxin. In order to make the sandwich immunoassay protocol a general method for detecting other ciguatoxins congeners, the preparation of mAbs for the left-end of ciguatoxin was investigated. Expeditious synthesis of the left end of ciguatoxin with installation of the 3-butene-1,2-diol side-chain of the A-ring as well as surface plasmon resonance (SPR) analysis of the antibody-hapten interactions are also described.

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Enantioselective synthesis of the AB ring fragment of gambiertoxin 4B. Implication for the absolute configuration of gambiertoxin 4B and ciguatoxin

Cited by 52 publications

References 7 publications

Total synthesis and related studies of large, strained, and bioactive natural products

Total synthesis and related studies of large, strained, and bioactive natural products

Palladium‐Catalyzed O‐Allylation of α‐Hydroxy Carbonyl Compounds

Bioorganic Studies Utilizing Rationally Designed Synthetic Molecules: Absolute Configuration of Ciguatoxin and Development of Immunoassay Systems

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