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.     

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.     

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.     

Rapid synthesis of the A-E fragment of ciguatoxin CTX3C

The A-E fragment of the marine natural product CTX3C has been prepared in an efficient manner by using a strategy in which two-directional and iterative ring-closing metathesis (RCM) reactions were employed for ring construction.     

Convergent synthesis of the ABCDE-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 convergent synthesis of the pentacyclic left half of C-CTX-1, based on a newly developed acyl radical strategy.     

A convergent synthesis of the right-hand fragment of ciguatoxin CTX3C

A convergent synthesis of the right-hand fragment of ciguatoxin CTX3C was investigated. The first and second generation stereocontrolled syntheses of the LM ring fragment were achieved via spiroacetalization as a key step, respectively. The polyether framework of the HIJKLM ring fragment was constructed in a convergent manner by using intramolecular allylation, ring-closing metathesis, and stereoselective hydrogenation to form the 36-methyl substituent as the key transformations.     

Synthesis of symmetric HIJ-ring model of ciguatoxin

A tricyclic model ether compound comprising 6/8/6 ether rings was synthesized via a new route including conjugate addition to form a symmetric eight-membered ether-ketone with syn/trans stereochemistry in selective manner. The corresponding vinyl triflate of this ketone was allowed to convert to the vinyl methyl derivative via cross-coupling reaction. This endo-olefinic tetrahydro-2H-oxocin was selectively reduced to afford α-methyl product. The corresponding exo-olefinic oxocane derivative, on the other hand, provided the β-methyl isomer as the major diastereoisomer (2/1). Our previous report on the synthesis of this final product was revised due to some rearrangement and the mechanisms are discussed.     

Total synthesis of ciguatoxin CTX3C: a venture into the problems of ciguatera seafood poisoning

After a twelve-year struggle, the total synthesis of ciguatoxin CTX3C has been achieved. Annually, more than 20,000 people worldwide suffer from ciguatera seafood poisoning. The extremely small amounts of the causative neurotoxin, ciguatoxin, in fish hampered the isolation, structural elucidation, detailed biological study, and preparation of anti-ciguatoxin antibodies for detecting these toxins. The large (3 nanometers long) and complicated molecular structure of ciguatoxins hindered chemists from completing a total synthesis. The chemical synthesis of CTX3C, determination of the absolute configuration, and synthesis-based preparation of the monoclonal antibodies as well as the effect of synthetic CTX3C on voltage-sensitive sodium channels are outlined.     

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]     

甲瓦龙酸内酯的合成

：本文采用实验室常见且价廉的丙酮、甲醛、乙酸酐、叔丁醇及异氯丙烷为原料，通过醛酮缩会、酸酐酰化、格氏反应等方法，合成了甲瓦龙酸内酯，收率达到35％-45％。经元素分析、红外分析及折光率测定，表明最终产物确是甲瓦龙酸内酯。     

Synthetic Studies on Ciguatoxin—Synthesis of H–I–J Ring System

Synthesis of a tricyclic ring system corresponding to H–I–J rings of ciguatoxin was stereoselectively achieved in 13 steps from a sugar derivative as a model study directed toward the total synthesis of ciguatoxin.     

Convergent synthesis of the E'FGH ring fragment of ciguatoxin 1B via an acetylene cobalt complex strategy

A convergent synthesis of the E'FGH ring fragment 28 of ciguatoxin 1B, a principal toxin causing widespread seafood poisonings "ciguatera", has been accomplished through (i) coupling between the E' ring-acetylide 9 and the H ring-aldehyde 20, (ii) stereoselective F ring cyclization via an acetylene cobalt complex, (iii) conversion to a carbonyl function under high-pressure hydrogenation, and (iv) reductive hydroxyketone cyclization to construct the G ring. In the (1)H NMR analysis of 28 at room temperature, a considerable broadening phenomenon was observed due to the slow conformational changes of the FG ring, as reported for natural ciguatoxin 1B. When measured in pyridine at -20 degrees C, the spectra of 28 exhibited a 3.5:1 mixture of two conformational isomers (UP and DOWN conformers).     

Convergent synthesis of the E'FGH' ring fragment of ciguatoxin 1B via an acetylene cobalt complex strategy

[reaction: see text] A convergent synthesis of the E'FGH' ring fragment of ciguatoxin has been accomplished through (i) coupling between the E' ring-acetylide and the H' ring-aldehyde, (ii) stereoselective F ring cyclization via an acetylene cobalt complex, (iii) conversion to a carbonyl function, and (iv) reductive hydroxy-ketone cyclization to construct the G ring.     

Studies on the Total Synthesis of Pseudolaric Acid A Stereocontrolled Synthesis of the Seven-membered Lactone

PseudolaricacidAwasisolatedfromPseudolariXkaempferiGord,aChinesemedicinalherbwhichexhibitsantifungalandantifertilityactivities'.Itisaditerpenicacidwithatransfusedhydroazuleneskeletoncontainingfourchiralcenters'.Accordingtotheretrosyntheticanalysis,thetricyclisskeletonofIcouldbeconstructedbyastereoselectiveintramolecular[4 3]cycloadditionfromaseven-memberedlactone4(Schemel).Inthiscommunication,wewouldliketoreportanefficient,stereo-andregio-selective,synthesisoflactone4.Thesynthesisbeganwitht…     

Synthesis and properties of oil-soluble butyl crystal violet lactone

A novel compound of butyl crystal violet lactone (BCVL) has been prepared by oxidizing leuco butyl crystal violet lactone (LBCVL), which was obtained by the mixture of N,N-dibutylaniline, p-(dibutylamino) benzaldehyde and methyl-m-(dibutylamino) benzoate. The structure of BCVL was characterized by ¹H-nuclear magnetic resonance (NMR), infrared (IR), and mass spectrometry (MS). The color of BCVL can change reversibly in some acid or alkali solvents. The result of the dissolution experiment showed that solubility of BCVL in organic solvent was improved compared with crystal violet lactone (CVL). Translated from Journal of Fudan University (Natural Science), 2006, 45(3): 375–379 [译自: 复旦学报(自然科学版)]     

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 Hemigossypol and its Derivatives

Hemigossypol (3), a sesquiterpene natural product, was previously isolated from Gossypium barbadense and was shown to display improved anti-fungal activity compared to gossypol (1), the disesquiterpene dimer of hemigossypol (3). Gossypol exhibits multiple biological activities. In order to study whether hemigossypol and its derivatives retain the various bioactivities of gossypol, we developed a short and convenient synthetic scheme to synthesize hemigossypol. This is the first de novo synthesis of this natural product. In addition derivatives of hemigossypol with various 2,5-alkyl substituents were synthesized. Modification of the synthetic scheme also afforded the natural product hemigossylic lactone (4) and its 2,5-substituted derivatives.     

一种结构新颖的螺锗化合物的合成

在吡啶存在下，本文利用手性配体试剂L-N，N-双(2-羟乙基)苏氨酸(1)与β-羧基乙基锗倍半氧化物(2)反应，首次得到一种具有旋光性、含δ-内酯环新颖结构的螺锗化合物(3)。^1H NMR ，IR和MS的测定数据均表明NGe配键是存在的。     

抗霉素合成概览

抗霉素(antimycin)是一大类具有九元环双内酯的天然抗生素, 最早发现于20世纪40年代末. 在随后的50多年中不断地有新的成员被发现, 到目前为止已多达26个. 这类化合物的结构主要是通过抗霉素A_3b来确定的, 所以合成工作也是围绕该成员展开的. 对文献中已有报道的合成工作加以综述, 对各方法的主要优缺点也进行了简要的分析.