The stereoselective construction of azaspiro[5.6]dodecenone skeletons by the chiral BOX/copper-mediated Diels-Alder reaction is described. The cycloaddition reaction of alpha-methylene caprolactams and functionalized dienes allows the concise formation of spirocyclic structures of marine phycotoxins, such as pinnatoxin and spirolide.

The synthesis of the ABCDEF-ring of ciguatoxin 3C was achieved via a route that included anion coupling of a dimethyldithioacetal mono-S-oxide derivative corresponding to the AB-ring and an aldehyde corresponding to the EF-ring, followed by cyclization using reductive etherification. The AB-ring was synthesized from a known d-glucose derivative based on ring-closing olefin metathesis, and the EF-ring was prepared by a process employing chirality-transferring Ireland-Claisen rearrangement and ring-closing olefin metathesis.

Pectenotoxin-2 (PTX2) is a shellfish toxin and has a non-anomeric spiroacetal, which is not stabilized by an anomeric effect. The selective construction of the non-anomeric spiroacetal has been a major problem in the synthesis of PTX2. Described herein is the stereoselective total synthesis of PTX2 via the isomerization of anomeric spiroacetal pectenotoxin-2b (PTX2b). The synthesis of PTX2b was achieved by a simple process including sulfone-mediated assembly of spirocyclic and bicyclic acetals and subsequent macrocyclization by ring-closing olefin metathesis. Finally, the selective construction of PTX2 was accomplished by the early termination of a dynamic transition process to equilibrium in the acid-catalyzed isomerization of anomeric PTX2b. [6,6]-Spiroacetal pectenotoxin-2c (PTX2c) was also synthesized from PTX2b. The cytotoxicity assay of the synthetic compounds against HepG2 and Caco2 cancer cells showed a potency of the order: PTX2≫PTX2b>PTX2c.

The C8–C20 segment of pectenotoxin-2 was efficiently synthesized in 16% overall yield in 22 steps from l-malic acid via an improved route.

In this study, we synthesized the C8–C20 and C21–C30 segments of the diarrhetic shellfish toxin pectenotoxin 2. The C8–C20 segment was assembled from a phosphonate corresponding to the C8–C15 segment (prepared from l-malic acid in 19 steps) and an aldehyde corresponding to the C16–C20 segment (synthesized from 3-methyl-3-butenol in nine steps) by a twelve-step process including the Horner–Wadsworth–Emmons reaction, regio- and stereoselective reduction of the resulting enone, diastereoselective epoxidation, and 5-exo epoxide cleavage forming the C-ring. The C21–C30 segment was constructed in 13 steps from (S)-glycidol via a route involving E-ring formation by 5-exo epoxide cleavage and stereoselective methylation at C27 by the Evans method.

Convergent synthesis of the IJKLM-ring part (2) of ciguatoxin CTX3C has been achieved from the I-ring and the L-ring parts (4 and 5) in total eight steps in 27% overall yield. The carbanion derived from 4, stabilized by a dimethyldithioacetal S-oxide group, was readily reacted with aldehyde 5 to give an adduct, which was facilely transformed into the corresponding α,ε-dihydroxy ketone 3. The JK-ring formation from 3 under reductive conditions followed by oxidative M-ring cyclization efficiently led to the pentacyclic ether 2. Improved synthesis of 6, a synthetic intermediate for 4, was also established.

ペルチェ効果を利用して雪結晶を生成する装置を考案した.本装置は,大型のペルチェ素子を多段化し水冷方式で使用する事により,室内で-30℃程度までの低温環境を実現しながら,電圧を調節することで,結晶生成領域の温度と水温,すなわち水面から発生する水蒸気量を変化させ,簡単に雪結晶を生成することができる対流型の人工雪発生装置である.筐体に発泡スチロールを使用するなどの工夫によって,装置の製作が容易であり,同時に小型で移動もできるという利点を持つ.これは,従来の対流型や拡散型装置のように低温室など大がかりな装置や,冷媒を使用する複雑な付加装置が不要である.本論文では,この装置の基本原理およびその構成を述べ,本装置によって作られた雪結晶のいくつかを紹介する.

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.

The common FGHI-ring part (2) of ciguatoxins has been synthesized from the F- and I-ring parts (6 and 5, respectively). The Nozaki–Hiyama–Kishi coupling of 6 with 5 followed by regio- and stereoselective epoxidation at C29 and C30 afforded an epoxide (4), which was transformed into a tricyclic compound (3) corresponding to the F-HI-ring part by 6-exo-epoxide opening and the subsequent inversion of the C29 stereocenter. Reductive cyclization of 3 forming the C31–O26 bond of the G-ring successfully produced 2.

The common left-half [C31–C33(OC1–C7)–C40] part of pectenotoxins has been synthesized convergently from the C31–C35, C36–C40, and C1–C7 parts. The C31–C35 part, prepared via a new route shorter than our previous route, was coupled with the C36–C40 part through reductive lithiation and addition reactions to give an adduct stereoselectively, which was converted to a cyclic acetal corresponding to the C31–C40 part. The left-half was synthesized by a three-step process including esterification of the C31–C40 part with the C1–C7 part.

AbstractFor Abstract see ChemInform Abstract in Full Text.

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.

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.

A synthetic method for a branched ether system was developed. The method was based on Lewis-acid-promoted gamma-position selective reduction of a gamma-alkoxy beta,gamma-unsaturated alpha-silyloxy nitrile, prepared through a process including intermolecular hetero-Michael reaction of a 2-butynoate ester derivative with an alcohol. The method was efficiently applied to the synthesis of fused medium-ring ethers involving the EF-ring segment (2) of ciguatoxin (1). (C) 2004 Elsevier Ltd. All rights reserved.

ChemInformVolume 35, Issue 43 Natural Products Formal Total Synthesis of Hemibrevetoxin B by a Convergent Strategy. Kenshu Fujiwara, Kenshu Fujiwara Dep. Chem., Grad. Sch. Sci., Hokkaido Univ., Sapporo 060, JapanSearch for more papers by this authorDaisuke Sato, Daisuke Sato Dep. Chem., Grad. Sch. Sci., Hokkaido Univ., Sapporo 060, JapanSearch for more papers by this authorManabu Watanabe, Manabu Watanabe Dep. Chem., Grad. Sch. Sci., Hokkaido Univ., Sapporo 060, JapanSearch for more papers by this authorHiroshi Morishita, Hiroshi Morishita Dep. Chem., Grad. Sch. Sci., Hokkaido Univ., Sapporo 060, JapanSearch for more papers by this authorAkio Murai, Akio Murai Dep. Chem., Grad. Sch. Sci., Hokkaido Univ., Sapporo 060, JapanSearch for more papers by this authorHidetoshi Kawai, Hidetoshi Kawai Dep. Chem., Grad. Sch. Sci., Hokkaido Univ., Sapporo 060, JapanSearch for more papers by this authorTakanori Suzuki, Takanori Suzuki Dep. Chem., Grad. Sch. Sci., Hokkaido Univ., Sapporo 060, JapanSearch for more papers by this author Kenshu Fujiwara, Kenshu Fujiwara Dep. Chem., Grad. Sch. Sci., Hokkaido Univ., Sapporo 060, JapanSearch for more papers by this authorDaisuke Sato, Daisuke Sato Dep. Chem., Grad. Sch. Sci., Hokkaido Univ., Sapporo 060, JapanSearch for more papers by this authorManabu Watanabe, Manabu Watanabe Dep. Chem., Grad. Sch. Sci., Hokkaido Univ., Sapporo 060, JapanSearch for more papers by this authorHiroshi Morishita, Hiroshi Morishita Dep. Chem., Grad. Sch. Sci., Hokkaido Univ., Sapporo 060, JapanSearch for more papers by this authorAkio Murai, Akio Murai Dep. Chem., Grad. Sch. Sci., Hokkaido Univ., Sapporo 060, JapanSearch for more papers by this authorHidetoshi Kawai, Hidetoshi Kawai Dep. Chem., Grad. Sch. Sci., Hokkaido Univ., Sapporo 060, JapanSearch for more papers by this authorTakanori Suzuki, Takanori Suzuki Dep. Chem., Grad. Sch. Sci., Hokkaido Univ., Sapporo 060, JapanSearch for more papers by this author First published: 01 October 2004 https://doi.org/10.1002/chin.200443221Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume35, Issue43October 26, 2004 RelatedInformation

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 beta,gamma-unsaturated alpha,epsilon-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). (C) 2004 Elsevier Ltd. All rights reserved.

Natural trans-fused polycyclic ethers, produced by marine Sources such as dinoflagellates, are hypothesized to be constructed efficiently from the corresponding polyepoxide precursors by a cascade of ring-closure reactions. The efficiency of the biogenetic pathway has been attractive for synthetic chemists and has prompted them to develop new methods for the construction of cyclic ethers from epoxides. In this review, recent advances in the synthesis of trans-fused polycyclic ethers by hydroxy-epoxide-cyclization reactions via monocyclic epoxonium ion intermediates and ether-ring-expansion reactions via bicyclic epoxonium ion intermediates are described.

Efficient construction of the respective right and left segments of azadirachtin is described. Furthermore, studies on the connection between both the segments are also mentioned; the Ireland-Claisen rearrangement of Li-enolate of the modelled ester with dichlorodimethylsilane in toluene afforded the desired limonoid framework stereoselectively in good yield.