Natural polyether

Clark s group also reported on ring-closing enyne metathesis for the preparation of six- and seven-membered cyclic enol ethers 428 n= 1,2) as potential building blocks for the synthesis of marine polyether natural compounds such as brevetoxins and ciguatoxins. Metathesis products 428 were obtained from ene-ynes 427 in 72-98% yield when the NHC-bearing catalyst C was used (Scheme 84) [179]. 

Ciguatoxin. The toxin was isolated from moray eels and purified to crystals by Scheuer s group (1). Structural determination of the toxin by x-ray or NMR analyses was unsuccessful due to the unsuitability of the crystals and due to the extremely small amount of the sample. The toxin was presumed to have a molecular formula of C Hg NO from HRFAB-MS data (MH+, 1111.5570) and to have six hydroxyls, five methyls, and five double bonds in the molecule (2). The number of unsaturations (18 including the five double bonds) and the abundance of oxygen atoms in the molecule point to a polyether nature of the toxin. The toxin, or a closely related toxin if not identical, is believed to be the principal toxin in ciguatera. Ciguatoxin was separable on an alumina column into two interconvertible entities presumably differing only in polarity (J). 

Negishi E, Tan Z (2005) Diastereoselective, Enantioselective, and Regioselective Carbo-alumination Reactions Catalyzed by Zirconocene Derivatives. 8 139-176 Netherton M, Fu GC (2005)Palladium-catalyzed Cross-Coupling Reactions of Unactivated Alkyl Electrophiles with Organometallic Compounds. 14 85-108 NicolaouKC, KingNP, He Y (1998) Ring-Closing Metathesis in the Synthesis of EpothUones and Polyether Natural Products. 1 73-104 Nishiyama H (2004) Cyclopropanation with Ruthenium Catalysts. 11 81-92 Noels A, Demonceau A, Delaude L (2004) Ruthenium Promoted Catalysed Radical Processes toward Fine Chemistry. 11 155-171... 

Ring-Closing Metathesis in the Synthesis of Epothilones and Polyether Natural Products... 

The impetus for developing this technology was provided by the continuing need for methodology amenable to the preparation of polycyclic arrays that constitute the frameworks of numerous polyether natural products such as the bre-vetoxins, ciguatoxin and maitotoxin 124 (Fig. 3). 

Rearrangement of the epoxy ester 317 affords a 1 1 mixture of the tetrahydropyran 318 and a steroidal tetra-hydrofuran by-product. This methodology offers a new hypothesis regarding the biosynthesis of polyether natural... 

Nicolaou KC, King NP, He Y (1998) Ring-Closing Metathesis in the Synthesis of Epothilones and Polyether Natural Products. 1 73 -104 Nishiyama H (2004) Cyclopropanation with Ruthenium Catalysts. II 81-92... 

The question of oxidative cyclization versus a polyepoxide cascade in the biosynthesis of polyether natural products has been reviewed <1995AGE298>. Enzymatic domino reactions involving epoxide intermediates have been reviewed <2001CSR332>. The DNA-damaging activity of epoxides and other oxidized species has been examined using chemical models <1995ACR289>. 

Nicolaou, K. C., King, N. P., He, Y. Ring-closing metathesis in the synthesis of epothilones and polyether natural products. Top. 

Yamamoto [106] and Martin [107] have independently investigated the exo cyclizations of (y-alkoxyallyl)stannanes, potential precursors to polyether natural products. Yamamoto systematically studied the thermal and Lewis acid-promoted cyclizations of allylstannanes (Z)-170 and ( )-171 (Table 11-11). 

Scheme 5.2.32 Intra-molecular allylations for the synthesis of polyether natural products 5.2.8 Reactions of Af-Acyliminium Cations...

The polyether natural products have provided an excellent testing ground for oxygen heterocyclic synthesis, and have also inspired many new methods. Nicolaou s group has shown that in contrast to the usual mode of cyclization onto an epoxide, the... 

A group of polycyclic polyether natural products are of special interest owing to their fascinating structure and biological activities. One of the proposed biosynthetic origins of these molecules features an epoxide-opening cascade pathway. Shi asymmetric epoxidation of un-activated alkenes has been frequently employed in the preparation of polyepoxide intermediates. McDonald and co-workers studied a series of tandem e 7o-selective and stereospecific oxacyclization of polyepoxides mediated by Lewis acid. Polyepoxides, such as 64, can be obtained from the epoxidation of triene 63 with ketone 2. Furthermore, a cascade cyclization, initiated by a Lewis acid-promoted epoxide opening of 64, furnished the desired polyether 65. 

Recent progress in the synthesis of oxepanes and medium ring ethers. Tetrahedron, 68, 6999-7018. (d) Vilotijevic, L, Jamison, T. F. (2009). Epoxide-opening cascades in the synthesis of polycyclic polyether natural products. Angewaudte Cheruie lutematioual Edition, 48, 5250-5281. (e) Snyder, N. L., Haines, H. M., Peczuh, M. W. (2006). Recent developments in the synthesis of oxepines. Tetrahedron, 62, 9301-9320. (f) For medium-ring thiacycles Rosowsky, A. 1972. In Weissberger, A., Taylor, E. C. (Eds.) Heterocyclic Compounds. Wiley, New York. Vol. 26. 

A number of approaches to components of polyether natural products have been reported. Several diastereoisomers of a part of the 32 ring polyether antibiotic maitotoxin have been prepared to establish configurations in the C63-C68 alicyclic portion of the natural product (by NMR comparisons). The D-glucose derived 197 [Tetrahedron Lett. 1994, 35, 5023] was converted to 198 and 199, which were then coupled to afford 200 and 3 diastereoisomers. NMR indicated that 200 has the relative stereochemistry of the natural product. 

Reference PPO content (wt%) More reactive polyether Nature Content (wt%) Catalyst content (wt%) Time (min)... 

---