Polycyclic ether

Stereocontrolled synthesis of polycyclic ethers and related heterocycles via intramolecular reactions of allylstannanes 97YGK619. 

Chemical realization of the biogenetic pathways proposed for fused polycyclic ethers of marine origin 99H(50)561. 

Synthetic study on marine polycyclic ethers and total synthesis of hemibreve-toxin B 98YGK940. 

Biomimetic synthesis of natural nonfused polycyclic ethers by metal oxide-induced. syn-oxidative polycyclizations of hydropolyenes 98PAC355. 

This lithiated epoxysulfone cyclisation strategy has been iteratively applied in the total synthesis of hemibrevitoxin B, a polycyclic ether marine toxin from the red tide organism Gymnodinium breve (Scheme 5.41) [64]. 

As in nature, the fonnation of adjacent THF ring chains or fused THP ring polycyclic ethers depends on the regioselectivity (endo or exo) of the nucleophilic addition to each epoxide (Scheme 8.16). 

Tandem 5-exo-oxacyclizations of polyepoxides to form polycyclic ethers are well known. In Evans s synthesis of lonomycin A, diepoxide 66 underwent the desired... 

In the synthesis of the squalenoid glabrescol (72 originally attributed structure), containing five adjacent (all cis) THF rings, the necessary precursor of the polyepoxide cascade, the pentaepoxide 71, was achieved by epoxidation of each of the trisubstituted double bonds of the known (R)-2,3-dihydroxy-2,3-dihydrosqualene (70) by the Shi epoxidation approach (Scheme 8.18) [34]. Treatment of 71 with CSA at 0 °C and subsequent purification by column chromatography provided the pure polycyclic ether 72 by a cascade process reasonably initiated by the free secondary alcohol functionality [35a]. 

Sasaki M (2006) Recent Advances in Total Synthesis of Marine Polycyclic Ethers. 5 149-178 Satake M (2006) Marine Polyether Compounds. 5 21-51 Shan R, see Maiti SN (2006) 2 207-246... 

Furthermore, iterative approaches are useful methods to construct polyhydroxy chains with 1,2- or 1,3-diol units of any length as chiral precursors for the synthesis of complex natural products [57] because automated synthesis becomes feasible. A preparation of trans-fused polytetrahydropyranes as structural unit for polycyclic ether biotoxines by repeated reaction sequences was recently named reiterative synthesis [58]. 

Using this methodology, cyclic ethers of different ring-size can also be constructed. Due to the fact that many natural products of marine origin include fused polycyclic ether structural units, a convenient entry to this structural element is of continuing challenge. 

McDonald and coworkers studied a series of tandem endo-selective and stereospecific oxacyclization of polyepoxides by reaction with Lewis acid [92-95]. Polyepoxides, such as 50, can be obtained from the epoxidation of triene 49 with ketone 26 (Scheme 8). This cascade cyclization of polyepoxides provides an efficient method to synthesize substituted polycyclic ether structures, which are present in a number of biologically active marine natural products. 

Polycyclic ethers are biosynthesized by a variety of microorganisms. Several were clinical antibiotic candidates in the 1960 s and 1970 s. The discovery that such substances may have a wide distritution in the marine environment raises intriguing questions. Is the genetic capability of directing the biosynthesis of polycyclic ethers widely distributed What are the functions of these substances ... 

One of the important challenges in modern synthetic and pharmaceutical chemistry is to design and develop efficient, clean, and fast routes to obtain architectural molecules from simple starting materials [102, 103]. The ewdo-selective cydoisome-rization (Scheme 4.13a) of terminal alkynes tethered to alcohols, nitrogen, and sulfur nudeophiles is one of the interesting transformations widely utilized in effident syntheses of antiviral nucleosides [104, 105], polycyclic ethers [106], and oligosac-... 

Disubstituted dihydropyrans are produced with high u/iri-selectivity when 2-phenyl-4-(4-tolylsulfonyl)-3,4-dihydro-2H -pyrans ate treated with Al-based Lewis acids <99SL132>. Tetraenes 10, derived from dienes via their epoxides, undergo a double RCM reaction under Ru-catalysis to yield polycyclic ethers 11 in which the dihydropyran units can be joined by a variable number of carbon atoms <99JOC3354>. Continued work on the use of dispiroketals in synthesis has led to an improved route to the enantiomers of bi(dihydropyrans) 12 <99JCS(P1)1639>. 

There are reports of many iterative cyclization strategies for the synthesis of fused polycyclic ethers related to marine natural products, for example, an Sml2-induced reductive cyclization <1999TL2811, 2002T1853> cyclic... 

The dicobalt octacarbonyl-promoted Nicholas reaction has been used in the preparation of polycyclic ethers related to the marine polyethers ciguatoxin 32 and gambiertoxin <1999JOC37>. 

Cycloaddition of oxazoles with arynes provides a route to substituted polycyclic ethers and hydrocarbons (80TL3627). Oxazole (354), for example, reacted with anthranilic acid and isoamyl nitrite to provide the cyclic ether (357) by way of the benzofuran (356). The ether was then treated with zinc in glacial acetic acid to furnish hydrocarbon (358) in 70% yield based on the starting oxazole (Scheme 77). 

RRM has been implemented in the synthesis of fused carbocycles9 as well as a number of polycyclic ethers.10 This has been extended to the synthesis of piperidines and pyrrolidines via ROM-RCM or RCM-ROM-RCM combinations (Figure 3). 

Boron trifluoride etherate promotes the fWt/a-selcctivc oxacyclization of polyepoxides derived from various acyclic terpenoid polyalkenes, including geraniol, farnesol, and geranylgeraniol, providing an efficient and stereoselective synthesis of substituted oxepanes and fused polyoxepanes. The oxacyclization transformations may mimic ringforming steps in the biosynthesis of trans-syn-trans-fused polycyclic ether marine natural products <2002JOC2515>. 

Formation of 5-membered cyclic ethers is favored in cyclization of cis-hydroxy epoxides (equation III). The cyclization can be extended to bicyclic or even polycyclic ethers. 

An intramolecular acyl radical cyclization of acyl selenide 1024 uses a (Z)-vinylogous sulfonate to control rotamer population, affording ry -2,6-disubstituted tetrahydropyran-4-one 1025, a key intermediate during synthesis of the tetrahydropyran unit of mucocin (Equation 399) <1997TL5249>. This methodology is also applicable to the synthesis of polycyclic ethers <1996JOC4880>. 

In nature, there are many kinds of polycyclic ether antibiotics, so this method can be used for the construction of polycyclic ethers. Eq. 6.8 shows the preparation of spiro sugar ketals (15) at anomeric position [21-23]. Biologically attractive spiro-nucleosides at the anomeric position may be prepared by this procedure. 

Yamamoto and co-workers reported an exquisite approach to the CDEFG ring system of gambierol (a polycyclic ether natural product) via intramolecular allylation of an a-acetoxy ether followed by RCM <01 JA6702> (Scheme 48). 

A number of reports have appeared on the use of carbonyl-alkene additions to construct oxacyclic ring systems efficiently with high diastereoselectivity. Nakata showed that even the formation of seven-membered cyclic ethers using the transformation can be remarkably efficient and utilised the strategy to form the E ring of the polycyclic ether marine natural product yessotoxin (Scheme 5.34).64... 

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