Polycyclic ethers, synthesis

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

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]. 

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]. 

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... 

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>. 

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>. 

Nakata utilised the Sml2-mediated Barbier-type cyclisation of a primary iodide with an ester as part of a convergent synthesis of trans-fused 6,6,6,6-tetracyclic ethers, which are typically found in marine polycyclic ethers.62 Treatment of iodide 50 with excess Sml2 in the presence of 1 mol% of Nil2 led to the smooth formation of intermediate hemiacetal 51, which was dehydrated to give dihy-dropyran 52 that was then further elaborated to give tetracycle 53 (Scheme 7.23).62... 

The synthesis of polycyclic ethers with variable ring sizes can be conducted by two-directional double ring-closing metathesis. This methodology was used to prepare, in one-step, the tricyclic ether 73, which has a six-, seven-, and eight-membered ring (Scheme 9) <2000AGE372>. 

Kadota, I., Ohno, A., Matsuda, K., and Yamamoto, Y. 2002. Convergent synthesis of polycyclic ethers via the intramolecular allylation of alpha-acetoxy ethers and subsequent ring-closing metathesis. Journal of the American Chemical Society 124, 3562-3566. 

Mori, Y, and Hayashi, H. 2002. Synthetic studies of yessotoxin, a polycyclic ether implicated in diarrhetic shellfish poisoning convergent synthesis of the BCDE ring system via an alkyne intermediate. Tetrahedron 58, 1789-1797. 

Recent advances in the synthesis of trans-iused polycyclic ethers by hydroxy epoxide cyclization reactions via monocyclic epoxonium ion intermediates and ether ring expansion reactions via bicyclic epoxonium ion intermediates are described in a review by Fujiwara and Murai. Natural trans-iu eA polycyclic ethers (e.g., brevetoxin A and ciguatoxin), produced by marine sources such as dinoflagellates, are hypothesized to be constructed from the corresponding polyepoxide precursors by a cascade of ring-closure reactions, which has prompted much work in the development of new methods for the construction of cyclic ethers from epoxides <2004BCJ2129>. 

In place of the aryl halide or alkenyl halide, the corresponding phosphate or triflate have been employed for the above cross-coupling reaction (O Scheme 71) [102]. These substrates were easily prepared from the corresponding lactone. The reaction of alkenyl phosphate or triflate has frequently been employed in the synthesis of marine polycyclic ethers such as brevetoxin... 

In the laboratory of J.H. van Boom, the synthesis of highly functionalized c/s- and frans-fused polycyclic ethers of various ring sizes via radical cyclization of carbohydrate-derived p-(alkynyloxy)acrylates was developed/ The radical cyclization precursors were prepared iteratively and the terminal alkyne moieties were installed using the Corey-Fuchs procedure. 

The first total synthesis of the marine polycyclic ether toxin (-)-gambierol was accomplished in the laboratory of M. Sasaki. The introduction of the a,(3-unsaturation into the seven-membered H ring of the FGH tricyclic subunit proved to be problematic, because both the conventional selenium-based method and the Nicolaou oxidation with IBX failed. However, when the seven-membered ketone was treated with LiHMDS in the presence of TMSCI and EtsN, the corresponding silyl enol ether was formed, which was oxidized under Saegusa conditions to give the desired cyclic enone in high yield. Because of the small scale of the reaction, a large excess of Pd(OAc)2 was used in acetonitrile so the presence of a co-oxidant was not necessary. 

Kawamura, K., Hinou, H., Matsuo, G., Nakata, T. Efficient strategy for convergent synthesis of trans-fused polycyclic ethers based on an intramolecular Sml2-promoted cyclization of iodo ester. Tetrahedron Lett. 2003, 44, 5259-5261. 

Sasaki, M., Fuwa, H. Total synthesis of polycyclic ether natural products based on Suzuki-Miyaura cross-coupling. Synlett 2004, 1851-1874. 

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