Synthesis of the ABCD fragment of gymnocin-B

A convergent synthesis of the ABCD fragment of gymnocin-B was accomplished. The tetracyclic ether ring system was synthesized by the construction of the BC ring system via the oxiranyl anion alkylation and ring expansion reaction, followed by the formation of the five-membered A-ring via a stereoselective radical cyclization reaction of a neopentyl-type iodide.     

Convergent synthesis of the ABCDE ring fragment of ciguatoxins

Synthesis of the ABCDE ring fragment of ciguatoxins has been achieved in a highly stereocontrolled and convergent manner via the B-alkyl Suzuki-Miyaura coupling-based approach.     

Convergent synthesis of the FGHI ring segment of yessotoxin

A convergent synthesis of the FGHI ring segment of yessotoxin was achieved via the intramolecular allylation of an α-chloroacetoxy ether and subsequent ring-closing metathesis.     

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.     

Studies toward the total synthesis of gambieric acids, potent antifungal polycyclic ethers: convergent synthesis of a fully elaborated GHIJ-ring fragment

A stereocontrolled synthesis of a fully elaborated GHIJ-ring fragment of gambieric acids, which are potent antifungal polycyclic ether natural products, has been accomplished. The synthesis features convergent assembly of the tetracyclic polyether skeleton through aldol coupling/cyclodehydration/reductive etherification processes and stereoselective construction of the J-ring side chain by a CeCl₃-promoted Julia-Kocienski olefination.     

Stereoselective synthesis of the cyclic ether core of (+)-laurenyne

A concise enantioselective synthesis of the cyclic ether core of the marine natural product (+)-laurenyne has been accomplished using ring-closing metathesis for medium-ring construction.     

Synthetic entry to the ABCD ring fragment of gymnocin-A, a cytotoxic marine polyether

Synthetic entry to the ABCD ring fragment of gymnocin-A, a cytotoxic marine polyether, has been achieved based on the B-alkyl Suzuki-Miyaura coupling-based strategy and radical cyclization for the construction of the tetrahydrofuran ring A.     

Synthesis of (+)-laurencin via ring expansion of a C-glycoside derivative

Laurencin was efficiently synthesized from a C-glycoside derivative based on ring expansion of the oxane part of the starting compound into an eight-membered cyclic ether via a ring-cleavage/ring-closing olefin metathesis process, stereoselective introduction of a bromo group at C4, and convergent construction of the side-chain part using a lithiated enyne unit.     

Convergent synthesis of the FGHI ring system of yessotoxin: stereoselective construction of the G ring

A convergent synthetic route to the FGHI ring system of yessotoxin, a marine ladder polyether, has been developed. The synthesis features convergent coupling of the diol and the aldehyde to form α-cyano ethers via acetal formation followed by ring closing metathesis and reductive etherification to construct the oxocane ring G and tetrahydropyran ring H, respectively. The β-methyl group on the G ring was stereoselectively introduced by alkylation of the corresponding ketone.     

A convergent approach to the formal total synthesis of hemibrevetoxin B

A convergent synthesis of the key synthetic intermediate of hemibrevetoxin B was achieved via the intramolecular allylation of an α-chloroacetoxy ether and subsequent ring-closing metathesis.     

Convergent synthesis of the ABCDE-ring part of ciguatoxin CTX3C

Convergent synthesis of the ABCDE-ring part (2) of ciguatoxin CTX3C (1) has been achieved. A carbanion stabilized by a dimethyldithioacetal S-oxide group in the AB-ring part (4) readily reacted with an aldehyde group in the E-ring part (5). The resulting adduct was facilely converted to the corresponding β,γ-unsaturated α,ε-dihydroxy ketone (3). The subsequent reductive hydroxy-ketone-cyclization reactions constructed the CD-ring part efficiently. Thus, the ABCDE-ring part (2) was concisely synthesized in 10 steps in 11% overall yield from the AB-ring and the E-ring parts (4 and 5).     

Formal total synthesis of hemibrevetoxin B by a convergent strategy

Concise construction of the trans-fused 7/7/6/6 tetracyclic ether part of hemibrevetoxin B (1) was achieved by a convergent strategy based on coupling reaction of an acyl anion equivalent, reductive cyclization of an α,ε-dihydroxyketone, and introduction of a methyl group at the central ring junction by the Nicolaou method. The resultant tetracyclic ether was transformed into the known intermediate, which was already converted to 1 by the Yamamoto group, thereby completing the formal total synthesis of 1.     

A new approach to the synthesis of cyclic ethers via the intermolecular allylation of α-acetoxy ethers and ring-closing metathesis

A concise synthesis of the isolaurepinnacin skeleton 6 was achieved via the intermolecular allylation of the α-acetoxy ether 3 followed by ring-closing metathesis. This methodology was successfully applied to the convergent synthesis of the oxocene 15, an advanced synthetic intermediate for the total synthesis of laurencin.     

Efficient and stereoselective installation of isoquinoline: formal total synthesis of cortistatin A

The highly stereoselective attachment of isoquinoline onto the steroidal framework of cortistatin A has been achieved. Our strategy features a Ce-mediated nucleophilic addition of an isoquinoline unit to the sterically congested ketone followed by formation of the phenyl thiocarbamate, and subsequent stereoselective radical reduction. The new method results in a formal total synthesis of cortistatin A.     

Design and synthesis of simplified polycyclic ethers and evaluation of their interaction with an α-helical peptide as a model of target proteins

Two simplified pentacyclic ethers, having 6/7/6/6/7 and 6/7/6/7/7 ring systems, were synthesized. A convergent route based on the Suzuki-Miyaura cross-coupling strategy was applied to synthesize these two compounds. Interactions between α-helical peptide, melittin, and synthesized pentacyclic ethers were evaluated by circular dichroism (CD) spectroscopy. Interestingly, only the polycyclic ether having a 6/7/6/7/7 ring stabilized the α-helical structure of melittin. This result indicated that a ring fusion manner of the polycyclic structure is important to recognize membrane proteins.     

Synthesis of the BC/DE ring model of brevisin for confirmation of the structure around the acyclic junction

Synthesis of the BC/DE ring model of brevisin, a polycyclic ether isolated from the red tide dinoflagellate Karenia brevis, is reported. Comparison of the NMR data of the BC/DE ring model with those corresponding to the same region of brevisin led to the confirmation of its structure around the acyclic juncture.     

Total synthesis and determination of the absolute configuration of (+)-neoisoprelaurefucin

The first total synthesis of the seven-membered ring ether marine natural product (+)-neoisoprelaurefucin (1) has been achieved employing a regioselective internal alkylation of amide 3, a novel sequence for removal of the triethylsilyl group from the resulting triethylsilyloxepene 2, and a bromoetherification of alcohol 16 as key steps. In addition, the absolute stereochemistry of the natural product was assigned.     

Chemistry of renieramycins. Part 11: Total synthesis of (±)-cribrostatin 4

A 19-step synthesis of (±)-cribrostatin 4 (1) from readily available piperazine-2,5-dione derivative 6 is described. The synthesis features the concise construction of a pentacyclic framework, followed by the base-catalyzed epimerization of the C-1 stereo center of aldehyde (11). The results of cytotoxicity studies are also presented.     

Concise total synthesis of phidianidine A and B

The shortest total synthesis of cytotoxic indole alkaloids phidianidine A and B is described. Rapid assembly of the 1,2,4-oxadiazole core from a novel N-hydroxyguanidine and the corresponding indole-3-acetic acid chloride led to formal syntheses of phidianidine A and B in only three steps from known compounds. Deprotection under standard conditions provided the trifluoroacetate salts of phidianidine A and B in quantitative yield.