Tetracyclic Ether Research Articles

Synthesis of chloroesters by the reaction of ethers with acyl chlorides catalyzed by ZnO

An efficient method for the synthesis of chloroesters by the reaction of ethers with acyl chlorides catalyzed by nano-ZnO under solvent-free condition at room temperature was described. The method is compatible with a range of ethers including tricyclic ethers, tetracyclic ethers, pentacyclic ethers and hexacyclic ethers and have afforded the products with moderate to good yields. The ZnO could be reused up to three times and the product yield after three cycles is 87%.

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.

ChemInform Abstract: Investigation of Oxidopyrylium—Alkene [5 + 2] Cycloaddition Conjugate Addition Cascade (C3) Sequences.

AbstractA series of bridged tetracyclic ethers is prepared with high diastereoselectivity via a novel oxidopyrylium—alkene cycloaddition—conjugate addition cascade reaction of readily accessible acetoxypyranone‐alkenes.

Stereoselective Synthesis of trans-Fused 7,6,6,7-Membered Tetracyclic Ether, Corresponding to the EFGH-Ring of Gambierol and the BCDE-Ring of Gambieric Acids

Stereoselective synthesis of a trans-fused 7,6,6,7-membered tetracyclic ether, corresponding to the EFGH-ring of gambierol and the BCDE-ring of gambieric acids, was efficiently accomplished via a two-directional approach. The key reactions were SmI(2)-induced double cyclization for construction of the F- and H-rings and SmI(2)-induced cyclization followed by ring expansion for construction of the E-ring.

Synthetic approaches to the polycyclic alkaloid stemofoline

Preliminary studies of a synthetic approach to the alkaloid stemofoline 1 are reported. Stereoselective cyclisation of the ketoester 14 gave the 1-butyl-2,8-bis(methoxycarbonyl)-8-azabicyclo[3.2.1]octane 21 in which the 2-methoxycarbonyl group is in the axial position. The analogous ketones 15, 18, and 19 were also cyclised to give the 8-azabicyclo[3.2.1]octanes 22-24 with axial electron-withdrawing 2-substituents. The structure of the bicyclic ketosulfone 22 was confirmed by X-ray diffraction. Conversion of ester 21 into the tricyclic lactams 31 and 39, in which the amide fragments are significantly distorted from planarity, was achieved by treatment of the iodides 29 and 38 with tert-butyllithium. The structure of the deprotected tricyclic hydroxylactam 40 was confirmed by X-ray diffraction, which showed the non-planar geometry of the lactam fragment and the distortion induced into the bicyclo[3.2.1]octane by the additional two-carbon bridge. This meant that the endo hydrogen at C9 was significantly closer to the 5-hydroxyl group than the endo hydrogen at C8. This structural feature was utilised to direct a regioselective remote oxidation of the hydroxylactam 40 using lead tetraacetate, which was accompanied by selective insertion into the closer endo C-H bond to give the tetracyclic ether 41. Lactam 39 was converted into the tricyclic aminoketone 49 by reduction to the aminol 44 using lithium aluminium hydride and reduction of the intermediate, possibly the chloride 46, formed from aminol 44 using thionyl chloride, with more lithium aluminium hydride, followed by O-deprotection and oxidation. The bicyclic ketoester 21 was also protected as its ketal 50, which was taken through via the tricyclic lactam 54 into the ketoamine 49. Finally, allylation of the tricyclic lactam 42 and amine 49 gave the axial allylated products 60 and 58, but further elaboration for incorporation of C10 and C11 (of stemofoline) was not straightforward. Alkylation of the protected hydroxyketone 64, which was prepared from the bicyclic ketoester 21, gave the axial alkylated products 65 and 69, and the ketoester 69 was converted into the tricyclic hydroxylactone 73. However, the formation of a tetracyclic lactam by treatment of the iodide 75 with tert-butyllithium was not successful.

Design and synthesis of an artificial ladder-shaped polyether that interacts with glycophorin A

Ladder-shaped polyether (LSP) compounds, such as brevetoxins and ciguatoxins, are thought to interact with transmembrane (TM) proteins. As a model LSP compound, we designed and synthesized an artificial tetracyclic ether ( 1) and evaluated its interaction with glycophorin A (GpA), a membrane protein known to dimerize or oligomerize between membrane-integral α-helical domains. Model compound 1 was found to induce the dissociation of oligomeric GpA in a similar manner to natural LSPs when examined by SDS–PAGE. The results suggest that even an artificial tetracyclic ether possesses the ability to interact with TM proteins, presumably through the intermolecular hydrogen bonds (C α–H ⋯ O) with the GXXXG motif.

Synthesis and evaluation of α-helix mimetics based on a trans-fused polycyclic ether: sequence-selective binding to aspartate pairs in α-helical peptides

Inspired by the topological similarity between ladder-like cyclic ether skeletons and α-helical peptides, a trans-fused 6/6/6/6 tetracyclic ether containing two hydroxyl groups separated by a distance of 4.8 Å was designed as a scaffold for a nonpeptidic α-helix mimetic. Two alkyl guanidinium groups were attached to the hydroxyl groups to develop a synthetic receptor for the specific recognition of i + 4 spaced aspartate pairs on the surface of an α-helical peptide. A circular dichroism (CD) titration showed that this mode of molecular recognition stabilizes α-helical structures of peptides containing i + 4 spaced aspartate pairs.

Internal Nucleophilic Termination in Acid‐Mediated Polyene Cyclizations Part 4

AbstractTreatment of the unsaturated bicyclic homoallylic alcohols (E)‐ and (Z)‐5 and (Z)‐ and (E)‐10 and allenic alcohol 16 with an excess of ClSO3H in 2‐nitropropane or CH2Cl2 at − 80° afforded, in moderate yields (ca. 30–70%), diastereoisomer mixtures of racemic tetracyclic ethers 12a–c (Table 1) and 17a,b (Table 2), respectively. These kinetically controlled stereospecific transformations are believed to proceed via concerted or nonconcerted pathways (see Schemes 4 and 6) and the results are fully consistent with our earlier work. Representing novel didehydro bridged analogues of known, olfactively active labdane tricyclic ethers, the organoleptic properties of 12a–c and 17a,b are briefly described, especially those of 12c which, in the context of structure–activity studies, is a racemic didehydro analogue of the known ambergris odorant Ambrox®.

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,e-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.

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 .

Convergent Synthesis of trans‐Fused 6/n/6/6 (n = 7, 8) Tetracyclic Ether System via α‐Cyano Ethers.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Efficient Strategy for Convergent Synthesis of trans‐Fused Polycyclic Ethers Based on an Intramolecular SmI2‐Promoted Cyclization of Iodo Ester.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Convergent synthesis of trans-fused 6/ n/6/6 ( n=7, 8) tetracyclic ether system via α-cyano ethers

A convergent method for synthesizing 6/ n/6/6 ( n=7, 8) tetracyclic ether system via two-rings construction of the central n/6 ring system was developed. The key steps of the present synthesis involve a ring-closing metathesis reaction for the construction of the seven- and eight-membered rings, and reductive etherification for the tetrahydropyrans. Unification of the two fragments through acetal formation, followed by regioselective cleavage of the acetal using TMSCN/TMSOTf in the presence of 2,6-di- tert-butyl-4-methylpyridine, afforded the α-cyano ether, of which the nitrile group was manipulated to give the precursors of the ring-closing reactions.

Divergent synthesis of the tetracyclic ethers of 6- X-7-6 ring systems

Ladder-shaped polyether natural products show diverse biological activities with extreme potency. As the initial phase of detailed SAR studies of bioactive polyethers, we set out to construct structurally simple mimics. This paper details the divergent synthesis of 6- X-7-6 tetracycles ( X=7, 8, or 9) starting from a simple 6-membered ether. Key reactions in the synthesis include (i) the direct formation of an O, S-acetal by the coupling of an alcohol with an α-chlorosulfide, (ii) the construction of a 7-membered ring by radical cyclization, and (iii) cyclization to the 7, 8 or 9-membered ring via a ring-closing metathesis reaction. The neutral reaction conditions of our strategy enable the synthesis of a wide variety of substrates. The results of this study can be applied for the rapid construction of artificial polyether compounds with diversified molecular shapes and sizes.

Efficient strategy for convergent synthesis of trans-fused polycyclic ethers based on an intramolecular SmI 2-promoted cyclization of iodo ester

An efficient convergent strategy for the construction of a trans-fused 6-6-6-6-membered tetracyclic ether ring system was developed. The key steps involve coupling of two cyclic ethers by esterification, SmI 2-promoted intramolecular reductive cyclization of iodo ester to hemiacetal, dehydration to dihydropyran, hydroboration, oxidation, intramolecular acetalization, and Lewis-acid catalyzed silane reduction.

Stereoselective convergent synthesis of a trans-fused polycyclic ether ring system including a 4-hydroxy-5-methyl-tetrahydropyran ring.

[reaction: see text] Stereoselective convergent synthesis of a trans-fused 6-6-6-6-membered tetracyclic ether ring system including 4alpha- or 4beta-hydroxy-5-methyl-tetrahydropyran was achieved. The key reactions involve the acetylide-aldehyde coupling of two tetrahydropyrans, intramolecular hetero-Michael cyclization of enone, stereoselective reduction of enone, hydroboration, intramolecular acetalization, and stereoselective reduction of the acetal with Et(3)SiH-TMSOTf.

Efficient convergent synthesis of a trans-fused 6-6-6-6-membered tetracyclic ether ring system

A very efficient convergent strategy for the construction of the trans-fused 6-6-6-6-membered tetracyclic ether ring system was developed based on the acetylide-triflate coupling of two tetrahydropyrans, oxidation of the alkyne group to an α-diketone, double cyclization to 6,6,6,6-membered tetracyclic diacetal, and stereoselective reduction of the diacetal with Et 3SiH–TMSOTf.

A Simple Convergent Method for the Construction of Fused Tri- and Tetracyclic Ethers

polycyclic ethers - acyl anion equivalent - dithioacetal S-oxide - acetal cyclization - reductive etherification

ChemInform Abstract: Convergent Synthesis of the trans‐Fused 6‐n‐6‐6 (n = 7‐10) Tetracyclic Ether System Based on a Ring‐Closing Metathesis Reaction.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Convergent synthesis of the trans-fused 6-n-6-6 (n = 7–10) tetracyclic ether system based on a ring-closing metathesis reaction

A convergent synthesis of the trans-fused 6-n-6-6 (n = 7–10) tetracyclic ether system was achieved via stereoselective alkylation and ring-closing metathesis reaction.