Synthesis of the JKLM-ring fragment of ciguatoxin

A stereoselective synthesis of the LM-ring fragment has been achieved starting from a sugar derivative. A stereoselective synthesis of the JKLM-ring fragment has been achieved through a coupling between two segments via heteroconjugate addition, seven-membered ether ring formation mediated by an acetylene cobalt complex, and spiroketalization reaction.     

Synthesis of the fully functionalized ABCDE ring moiety of ciguatoxin

A fully functionalized ABCDE ring moiety of ciguatoxin (CTX), the major causative agent of ciguatera poisoning, was synthesized for the first time. The present strategy involves the efficient installation of the C5-dihydroxybutenyl substituent and construction of the tetrahydrooxepin E ring using a novel alpha-chlorosulfide synthon. [structure: see text]     

Synthesis of the LMN-ring fragment of the Caribbean ciguatoxin C-CTX-1

Ciguatoxin C-CTX-1 was isolated as a principal causative toxin of ciguatera seafood poisoning in the Caribbean Sea, and is structurally classified as a ladder-shaped polycyclic ether. In this Letter, we report the synthesis of the tricyclic LMN-ring system of C-CTX-1. SmI₂-mediated reductive cyclization efficiently constructed the seven-membered M-ring with the axially oriented 1,3-dimethyl structure.     

Synthesis and Rheological Investigation ofModel Symmetric 3-Arm Star Polyethylene简

A variety of linear and 3-arm star polyethylene （PE） model polymers covering a wide range of molecular weight are synthesized by the living polymerization of butadiene and the subsequent hydrogenation. Several rheological parameters of these model linear and 3-arm star PE samples are analyzed for detecting the long chain branching （LCB） structure. It is found that the analyses based on zero shear viscosity, vGP plot and flow activation energy are very sensitive to the 3-arm star PEs. The information on the presence of LCB can be obtained with these methods even for low molecular weight samples, which can not be determined by GPC-MALLS. However the information about the LCB structure can not be obtained by the rheological methods alone.     

Synthesis of the C42-C52 part of ciguatoxin CTX3C

The C42-C52 part of ciguatoxin CTX3C (1) was synthesized from tri-O-acetyl d-glucal. The synthetic segment had a tetrahydropyran ring corresponding to the ‘C49-reduced’ L-ring of 1, designed to avoid side reactions due to acid-labile C49 acetal carbon during acidic reductive conditions planned in further synthesis toward 1. The vicinal dimethyl part at C47-C48 was constructed by a stepwise conjugate addition/methylation procedure. The C50-C52 unit was installed by Grignard addition of the C₃ unit followed by spirocyclization and reductive cleavage of the spirocyclic acetal. Stereoselective assembly of the C42-C44 part was achieved by Brown’s asymmetric crotylboration.     

Synthesis of highly symmetric mesomeric triazaphenalene betaines

The synthesis of seven mesomeric triazaphenalene betaines 4a‐g by condensation reaction of hexahydro‐2H‐pyrimido[1,2‐a]pyrimidine 1 with diethyl malonates 2a‐g or with bis(2,4,6‐trichlorophenyl)malonates 3c,f has been achieved. The guanidine 1 forms in benzene solution a salt with trimethyl methanetricarboxylate 5 which upon heating produces 4a.     

Synthesis of C2 symmetric triterpene bis-enaminones

Mono- and dicondensed triterpene enaminones were prepared by reaction of oleanane- and lupane-type 2hydroxymethylene derivatives with aliphatic and aromatic diamines in the presence of catalytic amounts of HOAc.     

Stereoselective synthesis of a KLM ring model of ciguatoxin: Confirmation of the C54 stereochemistry

A ciguatoxin KLM ring model and its C54 epimer were stereoselectively synthesized. Comparison of their ¹H NMR data with that on the natural toxin established the earlier stereochemical assignment at the C54 position.     

对称双-1,3,4-噁二唑化合物的合成及性质

首先以苯氧乙酰肼和二酰氯为原料反应得到对称双酰肼化合物,再以POCl3合环得到系列对称双-1,3,4-噁二唑化合物。考察了该系列化合物的紫外-可见吸收光谱,其中,间苯双-1,3,4-噁二唑化合物在250nm附近有明显的最大吸收峰,对苯双-1,3,4-噁二唑化合物的最大吸收峰则红移至290nm附近;而脂肪族双-1,3,4-噁二唑化合物没有明显的最大吸收峰,说明没有大的共轭体系,与结构相符合。所有化合物的结构均经元素分析、IR、1H NMR和MS确证。     

Convergent synthesis of the right-hand segment of ciguatoxin

[reaction: see text] A convergent synthesis of the right-hand half of ciguatoxin (the HIJKLM ring system) has been achieved with complete stereocontrol in the introduction of the stereocenters on the eight-membered I ring. Key steps are Sonogashira coupling, dicobalt complexation, intramolecular conjugate addition, and hydrogenation of an endo-olefin to provide the 39-alpha-methyl group.     

Synthesis of symmetric anhydrides using visible light-mediated photoredox catalysis

A new approach to anhydride formation is reported via activation of C-O bonds by the Vilsmeier-Haack reagent formed by Ru(bpy)(3)Cl(2) and CBr(4) in DMF. Various aryl and alkyl carboxylic acids are converted to the corresponding anhydrides in excellent yields.     

Synthesis of a novel, highly symmetric bis-oxa-bridged compound

A highly oxygenated, novel pentacyclic bis-oxa-bridged compound 8 was synthesized with remarkable efficiency starting from readily available tetrachloro-5,5-dimethoxyclopentadiene and 1,4-cyclohexadiene in three steps. The ruthenium-catalyzed oxidation of 2:1 bis-adduct 1 followed by a one-pot transformation of the resulting bis-alpha-diketone 3 furnished (after esterification) the title compound in an overall yield of 29.1%. The versatility of this simple method was further demonstrated with other norbornyl alpha-diketones to obtain the corresponding strained oxa-bridged derivatives.     

Stereoselective synthesis of the left wing of Caribbean ciguatoxin

Ciguatoxins, the principal causative toxins of ciguatera seafood poisoning, are potent toxic polycyclic ethers. In this paper, we report a stereoselective and secure route to the left wing of Caribbean ciguatoxin on the basis of a 6-exo radical cyclization strategy.     

Total synthesis of ciguatoxin and 51-hydroxyCTX3C

Ciguatoxins, the principal causative toxins of ciguatera seafood poisoning, are large ladder-like polycyclic ethers with the 13 ether rings ranging from five- to nine-membered. In this paper, we describe the total synthesis of the two most toxic members of the ciguatoxin family, ciguatoxin 1 and 51-hydroxyCTX3C 2, based on a unified synthetic strategy. The key features in our syntheses were (i) direct construction of the O,S-acetal from the corresponding left and right wing fragments (3, 4, 14); (ii) stereo- and chemoselective radical reaction of the alpha-oxyradical with pentafluorophenyl acrylate to achieve cyclization of the seven-membered G-ring; (iii) ring-closing metathesis reaction to build the nine-membered F-ring; and (iv) an efficient protective group strategy using the oxidatively removable 2-naphthylmethyl groups.     

A concise route to the right wing of ciguatoxin

A concise route to the HIJKLM-ring fragment 10 of ciguatoxin (CTX) and 51-hydroxyCTX3C was developed in which oxiranyl anion addition and intramolecular carbonyl olefination were utilized as key transformations. The present procedure requires only 23 steps from the I-ring 5, while 35 steps were employed in a previous synthesis of the corresponding right wing 11 of CTX3C. The high efficiency of the present synthesis ensures a supply of 10 for total synthesis and biomedical applications.     

Synthesis of a symmetric multivalent molecule containing four carbohydrate substituents

Summary Starting with allyl- and pent-4-enyl--D-glucopyranosides4–7, differentD-Glucose units (8–15) containing alkyl spacers of variable lenght and with different end groups can be prepared. Reaction of four equivalents of the caesium salt derived from propan-4-carboxy-1-yl-2,3,4,6-tetra-O-acetyl--D-glucopyranoside15 with pentaerythrityltetrabromide yields the tetravalent molecule16.

---

Synthese eines symmetrischen multivalenten Moleküls mit vier Kohlenhydratsubstituenten

Zusammenfassung Ausgehend von den Allyl- und Pent-4-enyl--D-glucopyranosiden4–7 können dieD-Glucosederivate8–15 dargestellt werden, welche am anomeren Zentrum unterschiedlich lange Spacereinheiten mit verschiedenen Endgruppen besitzen. Bei Reaktion von vier Äquivalenten des Caesiumsalzes von Propan-4-carboxy-1-yl-2,3,4,6-tetra-O-acetyl--D-glucopyranosid15 mit Pentaerythrityltetrabromid entsteht das tetravalente Molekül16.

     

A new stereoselective synthesis of ciguatoxin right wing fragments

The right wings (13 and 14) of ciguatoxins were synthesized highly stereoselectively. Key transformations in the synthesis are (i) an oxiranyl anion strategy to attach the H ring, (ii) intramolecular carbonyl olefination to cyclize the J ring, (iii) regio- and stereoselective reduction of the epoxyacetal to install the C42-stereocenter, and (iv) stereoselective reductive etherification to construct the K ring. The present procedure greatly improved the stereoselectivity and efficiency in comparison to a previous synthesis. Remarkably, only 23 steps were required from monocyclic I ring 5 to construct the ciguatoxin right wings. The high practicality of the present synthesis ensures a sufficient supply of these complex fragments for total syntheses and biomedical applications.     

Synthesis of the EF-ring of ciguatoxin 3C based on the [2,3]-Wittig rearrangement and ring-closing olefin metathesis

The EF-ring segment of ciguatoxin 3C, a causative toxin of ciguatera fish poisoning, was synthesized in three major steps: 1,4-addition for the C20O-C27 bond connection, chirality transferring anti selective [2,3]-Wittig rearrangement for the construction of the anti-2-hydroxyalkyl ether part, and ring-closing olefin metathesis for the F-ring formation.     

Synthesis of the EF-ring segment of ciguatoxin CTX1B based on novel regioselective reduction of unsaturated cyanohydrins and ring-closing olefin metathesis

Aiming at a convergent total synthesis of ciguatoxin CTX1B, its EF-ring segment has been synthesized. During the synthesis, a novel method for the construction of branched ethers, based on regioselective reduction of γ-alkoxy β,γ-unsaturated α-silyloxy nitriles with borontrifluoride etherate and trialkyl silane or tributyltin hydride, has been developed. Combination use of the method and ring-closing olefin metathesis successfully provided medium-sized cyclic ethers. Efficient site-selective reduction of vinyl epoxides into homoallyl alcohols has also been developed.