Subsequent Ring-closing Metathesis Research Articles

Evaluation of a cascade cyclization approach toward harringtonolide

An account of synthetic work directed toward the total synthesis of the cytotoxic cephalotaxus norditerpenoid, harringtonolide, is disclosed. An initial Lewis Acid-catalyzed Diels-Alder/Ene cascade was designed to construct a key 6,6,5-fused tricyclic building block in a single step. While this process could not be realized in a single pot, a three-step cycloaddition/Barbier-type sequence afforded this motif, and after subsequent ring-closing metathesis, the entire 7,6,6,5-fused core of the natural product was generated. This strategy could be of use in the synthesis of various cephalotane natural products containing 7-membered rings.

Base-mediated cascade synthesis of indole diolefins: a route to spiro[cyclopentene-indole]thiones and thiepino[2,3-b]indoles.

Base-mediated cascade reactions of 3-hydroxymethyl-3-propenylindole-2-thiones afforded diolefins and involved deformylation, thioenolate alkylation and the thio-Claisen rearrangement. Subsequent ring-closing metathesis reactions of the diolefins furnished 3-spiro[cyclopentene-indole]-2-thiones or thiepino[2,3-b]indoles.

Formal Syntheses of (-)-Lepadiformines A, C, and (-)-Fasicularin.

Marine tricyclic alkaloids lepadiformine and fasicularin, with a unique perhydropyrrolo[2,1- j]quinoline or perhydropyrido[2,1- j]quinoline framework, were synthesized starting from the B ring of the tricyclic system. This approach includes a highly stereocontrolled diallylation of a cyclic enaminoester and subsequent ring-closing metathesis to construct the A/B ring system, which was transformed into key lactams 32 and 33, and amino alcohol 37. Thus, we achieved formal syntheses of (-)-lepadiformines A, C, and (-)-fasicularin in a divergent manner.

Tandem Ring-Opening-Ring-Closing Metathesis for Functional Metathesis Catalysts.

Use of a tandem ring-opening-ring-closing metathesis (RORCM) strategy for the synthesis of functional metathesis catalysts is reported. Ring opening of 7-substituted norbornenes and subsequent ring-closing metathesis forming a thermodynamically stable 6-membered ring lead to a very efficient synthesis of new catalysts from commercially available Grubbs' catalysts. Hydroxy functionalized Grubbs' first- as well as third-generation catalysts have been synthesized. Mechanistic studies have been performed to elucidate the order of attack of the olefinic bonds. This strategy was also used to synthesize the ruthenium methylidene complex.

De Novo Synthesis of Furanose Sugars: Catalytic Asymmetric Synthesis of Apiose and Apiose-Containing Oligosaccharides.

A de novo synthetic method towards apiose, a structurally unusual furanose, is reported. The key feature is sequential metal catalysis consisting of the palladium-catalyzed asymmetric intermolecular hydroalkoxylation of an alkoxyallene and subsequent ring-closing metathesis (RCM). This strategy enabled the efficient synthesis of various apiose-containing disaccharides and a unique convergent synthesis of trisaccharides.

Stereoselective synthesis of a novel branched-chain (1S,2R,6R,7S)-7a-(hydroxymethyl)-1,2,6,7-tetrahydroxypyrrolizidine

An efficient and highly stereoselective approach towards a new type of branched-chain pentahydroxylated pyrrolizidine 7 from a d-glucose isothiocyanate scaffold has been developed. The key features of this strategy are the construction of a diene-substrate foldamer possessing an amino functional group followed by subsequent ring-closing metathesis, an intramolecular cyclisation readily induced by regioselective tosylation to establish the pyrrolizidine unit and a highly diastereoselective, substrate-controlled dihydroxylation.

Convergent synthesis of the EFGH ring system of ciguatoxin CTX3C

Convergent synthesis of the EFGH ring segment of ciguatoxin CTX3C was investigated by using the intramolecular allylation of an α-chloroacetoxy ether and/or O,S-acetal, and subsequent ring-closing metathesis. A new method for the preparation of γ-alkoxyallylstannane is also described.

ChemInform Abstract: Stereocontrolled Total Synthesis and Biological Evaluation of (‐)‐ and (+)‐Petrosin and Its Derivatives.

ChemInformVolume 46, Issue 13 Natural Products ChemInform Abstract: Stereocontrolled Total Synthesis and Biological Evaluation of (-)- and (+)-Petrosin and Its Derivatives. Hiroki Toya, Hiroki Toya Grad. Sch. Pharm. Sci., Tohoku Univ., Aoba, Sendai 980, JapanSearch for more papers by this authorTakahito Satoh, Takahito Satoh Grad. Sch. Pharm. Sci., Tohoku Univ., Aoba, Sendai 980, JapanSearch for more papers by this authorKentaro Okano, Kentaro Okano Grad. Sch. Pharm. Sci., Tohoku Univ., Aoba, Sendai 980, JapanSearch for more papers by this authorKiyosei Takasu, Kiyosei Takasu Grad. Sch. Pharm. Sci., Tohoku Univ., Aoba, Sendai 980, JapanSearch for more papers by this authorMasataka Ihara, Masataka Ihara Grad. Sch. Pharm. Sci., Tohoku Univ., Aoba, Sendai 980, JapanSearch for more papers by this authorAtsushi Takahashi, Atsushi Takahashi Grad. Sch. Pharm. Sci., Tohoku Univ., Aoba, Sendai 980, JapanSearch for more papers by this authorHaruo Tanaka, Haruo Tanaka Grad. Sch. Pharm. Sci., Tohoku Univ., Aoba, Sendai 980, JapanSearch for more papers by this authorHidetoshi Tokuyama, Hidetoshi Tokuyama Grad. Sch. Pharm. Sci., Tohoku Univ., Aoba, Sendai 980, JapanSearch for more papers by this author Hiroki Toya, Hiroki Toya Grad. Sch. Pharm. Sci., Tohoku Univ., Aoba, Sendai 980, JapanSearch for more papers by this authorTakahito Satoh, Takahito Satoh Grad. Sch. Pharm. Sci., Tohoku Univ., Aoba, Sendai 980, JapanSearch for more papers by this authorKentaro Okano, Kentaro Okano Grad. Sch. Pharm. Sci., Tohoku Univ., Aoba, Sendai 980, JapanSearch for more papers by this authorKiyosei Takasu, Kiyosei Takasu Grad. Sch. Pharm. Sci., Tohoku Univ., Aoba, Sendai 980, JapanSearch for more papers by this authorMasataka Ihara, Masataka Ihara Grad. Sch. Pharm. Sci., Tohoku Univ., Aoba, Sendai 980, JapanSearch for more papers by this authorAtsushi Takahashi, Atsushi Takahashi Grad. Sch. Pharm. Sci., Tohoku Univ., Aoba, Sendai 980, JapanSearch for more papers by this authorHaruo Tanaka, Haruo Tanaka Grad. Sch. Pharm. Sci., Tohoku Univ., Aoba, Sendai 980, JapanSearch for more papers by this authorHidetoshi Tokuyama, Hidetoshi Tokuyama Grad. Sch. Pharm. Sci., Tohoku Univ., Aoba, Sendai 980, JapanSearch for more papers by this author First published: 12 March 2015 https://doi.org/10.1002/chin.201513279Read 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 onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume46, Issue13March, 2015 RelatedInformation

Enantioselective synthesis of metacycloprodigiosin via the ‘Wasserman pyrrole’

A concise, nine-step enantioselective total synthesis of metacycloprodigiosin is reported. The synthesis provides increased step-efficiency over the previous racemic and enantioselective syntheses of this compound. Key features of the work include investigations into a convergent oxidative coupling reaction and subsequent ring-closing metathesis to deliver an advanced pyrrole intermediate we name the ‘Wasserman pyrrole’ that can be converted to metacycloprodigiosin in one step.

Stereocontrolled total synthesis and biological evaluation of (−)- and (+)-petrosin and its derivatives

Total synthesis of (−)- and (+)-petrosin was accomplished. Stereocontrolled construction of the quinolizidine ring was achieved through a diastereoselective Mannich reaction and an aza-Michael reaction. Head-to-tail dimerization was performed by assembly of the two monomers using Suzuki–Miyaura cross coupling and subsequent ring-closing metathesis to construct the 16-membered ring. Biological evaluation of synthetic (−)- and (+)-petrosin and its derivatives indicated that the bispiperidine structure was necessary for the inhibition of syncytium formation.

Synthesis of Orientationally Isomeric Cyclic Stereoblock Polylactides with Head-to-Head and Head-to-Tail Linkages of the Enantiomeric Segments

A pair of orientationally isomeric cyclic stereoblock polylactides (PLAs) possessing head-to-head (HH) and head-to-tail (HT) linkages between the poly(l-lactide) (PLLA) and poly(d-lactide) (PDLA) segments was synthesized through click chemistry and ring-closing metathesis (RCM) of three asymmetrically functionalized telechelic precursors. Thus, α-ethenyl-ω-azido-PLLA (2a) was reacted with α-ethenyl-ω-ethynyl-PDLA (2b) and α-ethynyl-ω-ethenyl-PDLA (2c) via click chemistry to form ethenyl telechelic stereoblock PLAs with HH and HT orientations (3a and 3b), respectively. The subsequent RCM produced cyclic stereoblock PLAs with the corresponding linking manners (4a and 4b). The effect of the topology on the melting temperature of the series of isomeric linear and cyclic PLAs having the contrastive linking orientations was systematically investigated.

Halocarbocyclization Entry into the Oxabicyclo[4.3.1]decyl Exomethylene-δ-Lactone Cores of Linearifolin and Zaluzanin A: Exploiting Combinatorial Catalysis

A streamlined entry into the sesquiterpene lactone (SQL) cores of linearifolin and zaluzanin A is described. Stereochemistry is controlled through transformations uncovered by ISES (In Situ Enzymatic Screening). Absolute stereochemistry derives from kinetic resolution of 5-benzyloxypentene-1,2-oxide, utilizing a β-pinene-derived-Co(III)-salen. Relative stereochemistry (1,3-cis-fusion) is set via formal halometalation/carbocyclization, mediated by [Rh(O(2)CC(3)F(7))(2)](2)/LiBr. Subsequent ring-closing metathesis (RCM-Grubbs II) yields the title exomethylene-δ-lactone SQL cores. In complementary fashion, RCM with Grubbs-I catalyst provides the oxabicyclo[3.3.1]nonyl core of xerophilusin R and zinagrandinolide.

Iridium-Catalyzed Allylic Vinylation and Asymmetric Allylic Amination Reactions with o-Aminostyrenes

An Ir-catalyzed allylic vinylation reaction of allyl carbonates with o-aminostyrene derivatives has been realized, providing skipped (Z,E)-diene derivatives. With (E)-but-2-ene-1,4-diyl dimethyl dicarbonate as the substrate, an efficient enantioselective synthesis of 1-benzazepine derivatives via an Ir-catalyzed domino allylic vinylation/intramolecular allylic amination reaction has been developed. Mechanistic studies of the allylic vinylation reaction have been carried out, and the results suggest that the leaving group of the allylic precursor plays a key role in directing the reaction pathway. Screening of various allylic precursors showed that Ir-catalyzed reactions of allyl diethyl phosphates with o-aminostyrene derivatives proceed via an allylic amination pathway. A subsequent ring-closing metathesis (RCM) reaction of the amination products led to a series of enantiomerically enriched 1,2-dihydroquinoline derivatives. Their utility is indicated by an asymmetric total synthesis of (-)-angustureine.

Synthesis and antibacterial activity of some binaphthyl-supported macrocycles containing a cationic amino acid

As part of a programme investigating antibacterial cyclic macrocycles containing a cationic amino acid with an internal aromatic hydrophobic scaffold, we previously reported a macrocycle anchored at the 3,3′-positions of a 1,1′-binaphthyl unit. This was prepared via key intermediates containing an internal allylglycine and an allyl-substituted binaphthyl unit for a subsequent ring-closing metathesis reaction. This paper presents some structure–activity relationship studies with additional macrocycles based on this lead compound against Staphylococcus aureus together with the antibacterial activity of two related acyclic compounds.

ChemInform Abstract: Total Synthesis of Brevenal.

A total synthesis of brevenal is described. The pentacyclic ether core was constructed by the intramolecular allylation of α-acetoxy ether and subsequent ring-closing metathesis. Both of the diene side chains were introduced by Wittig olefination and a Horner−Wadsworth−Emmons reaction, respectively, in a highly stereoselective manner.

Synthesis of Bivalent Lactosides Based on Terephthalamide, N,N′-Diglucosylterephthalamide, and Glycophane Scaffolds and Assessment of Their Inhibitory Capacity on Medically Relevant Lectins

Glycan recognition by lectins initiates clinically relevant processes such as toxin binding or tumor spread. Thus, the development of potent inhibitors has a medical perspective. Toward this goal, we report the synthesis of both rigid and flexible bivalent lactosides on scaffolds that include secondary and tertiary terephthalamides and N,N'-diglucosylterephthalamides. Construction of these compounds involved Schmidt-Michel glycosidation, and amide coupling or Ugi reactions of relevant glycosyl amines in key steps. A glycocluster based on a rigid glycophane was also prepared from coupling of a glucuronic acid derivative and p-xylylenediamine with subsequent ring-closing metathesis. Finally, a more flexible bivalent lactoside was produced from lactosyl azide with use of the copper-catalyzed azide-alkyne cycloaddition. Distances between lactose residues were analyzed computationally as were their orientations for the relatively rigid subset of compounds. Distinct spacing properties were revealed by varying the structure of the scaffold or by varying the location of the lactose residue on the scaffold. To relate these features to bioactivity a plant toxin and human adhesion/growth-regulatory galectins were used as sensors in three types of assay, i.e. measuring agglutination of erythrocytes, binding to glycans of a surface-immobilized glycoprotein, or binding to human cells. Methodologically, the common hemeagglutination assay was found to be considerably less sensitive than both solid-phase and cell assays. The bivalent compounds were less effective at interfering with glycoprotein binding to the plant toxin than to human lectins. Significantly, a constrained compound was identified that displayed selectivity in its inhibitory potency between galectin-3 and its proteolytically processed form. Conversely, compounds with a high degree of flexibility showed notable ability to protect human cells from plant toxin binding. The applied conjugation chemistry thus is compatible with the long-term aim to produce potent and selective lectin inhibitors.

Convergent synthesis of the A–E ring segment of ciguatoxin CTX3C

A convergent synthesis of the A–E ring segment of ciguatoxin CTX3C was achieved via the intramolecular allylation of an α-chloroacetoxy ether and subsequent ring-closing metathesis.

Total Synthesis of Brevenal

A total synthesis of brevenal is described. The pentacyclic ether core was constructed by the intramolecular allylation of alpha-acetoxy ether and subsequent ring-closing metathesis. Both of the diene side chains were introduced by Wittig olefination and a Horner-Wadsworth-Emmons reaction, respectively, in a highly stereoselective manner.

An Enantioselective Organocatalytic Approach to Both Enantiomers of Lasubine II

A concise stereoselective route providing access to both enantiomers of the bioactive quinolizidine alkaloid lasubine II has been developed. The enantioselectivity was introduced by taking advantage of a proline-catalyzed asymmetric Mannich reaction. Next, the bicyclic system was constructed via a diastereoselective Mannich cyclization and subsequent ring-closing metathesis as the key steps.

ATRP−RCM Synthesis of Cyclic Diblock Copolymers

A versatile synthetic means for cyclic diblock copolymers has been developed by the combination of atom transfer radical polymerization (ATRP) and ring-closing metathesis (RCM) techniques. Thus, first, an A−B type allyl-telechelic diblock copolymer comprised of two different acrylate ester segments, i.e., poly(methyl acrylate)-b-poly(n-butyl acrylate), poly(MA)-b-poly(BA), was prepared via the ATRP of MA, followed by the addition of the second monomer, BA, with allyl bromide as an initiator and with allyltributylstannane as an end-capping reagent, respectively. Alternatively, an A−B−A type allyl-telechelic triblock copolymer comprised of poly(BA) and poly(ethylene oxide), poly(EO), segments was prepared via the ATRP of BA using a poly(EO) macroinitiator having 2-bromoisobutyryl end groups, followed by the end-capping reaction with allyltributylstannane. The subsequent RCM of the allyl-telechelic block copolymers under dilution in the presence of Grubbs catalyst could afford the corresponding A−B type cyclic diblock copolymers.