Natural cyclic ether

Jung et al. s synthesis of aplysiapyranoid A 58, a cytotoxic monoterpene, also demonstrated another successful substrate-controlled route to the halogenated natural cyclic ether (Scheme 43.6). 2,4,4,6-Tetrabromocyclohexadie-none (TBCO) 55 triggered the cyclization of hydroxyl alkene 54, which after biomimetic bromoetherification, provided bromoether 57. The intermediacy of bromonium species 56, in which a stericaUy less demanding chloroal-kenyl substituent is positioned axially, is postulated to be responsible for the stereochemical outcome in this bromina-tive cyclization. 

Since 1950 a number of polyether antibiotics have been discovered using fermentation technol ogy They are characterized by the presence of sev eral cyclic ether structural units as illustrated for the case of monensm in Figure 16 3a Monensin and other naturally occurring polyethers are similar to crown ethers in their ability to form stable complexes... 

Figure 8.2 Examples of natural tram-fused cyclic ethers brevetoxin B and hemibrevetoxin B.

A highlight in the application of RCM methodology in natural product synthesis is Hirama s total synthesis of ciguatoxin CTX3C (183) [90], including the more recent improved protective group strategy, as depicted in Scheme 34 [90b]. The structure of 183 spans more than 3 nm and is characterized by 12 six- to nine-membered trans-fused cyclic ethers and a spiroannulated terminal tetra-... 

Cationic copolymerization of cyclic ethers, formals, esters and anhydrides has been thoroughly studied in recent years and sufficient information about it is now available. The propagating species involved in the cationic copolymerization of these oxacyclic monomers are believed to be the oxonium ions in most cases, but their detailed nature is dependent on monomer structure. From their copolymerization behavior, these monomers can be arranged in the following order of increasing car-bocationic character of the propagating species ... 

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. 

Cyclization of mixed acetals (13,300).4 This reaction is a particularly useful route to eight-membered cyclic ethers (oxocanes) and provides the first practical route to a natural oxocene, (- )-laurenyne (3), from an optically active mixed acetal 1. Thus cyclization of 1 followed by O-desilylation affords 2 as the only cyclic product. Remaining steps to 3 involved C-desilylation, for which only HF/pyridine is useful, introduction of unsaturation into the C2-side chain, and extension of the C8-side chain. Exploratory studies showed that unsaturation at the p- or y-positions to the cite of cyclization of 1 prevent or retard cyclization with a wide variety of Lewis acids. The cyclization is apparently more tolerant of substitution in the terminator position, C3-Q, of the oxocene. 

Aryltellnrinyl acetates, generated as previously described from the corresponding tellurinic anhydrides and acetic acid, add to hydroxy olefins, giving tellurinylated cyclic ethers. The reaction is performed in refluxing acetic acid or in chloroform in the presence of BFj EtjO. Owing to their hygroscopicity and intractable nature, the products are reduced with hydrazine hydrate, and isolated as tellurides (as for the aminotellurinylation reactions). 

The ability of cyclic ethers to complex biologically important alkylammonium cations makes the choice of crown ethers as enzyme binding site models a natural one. In recent years a number of molecules containing both a crown ether-based substrate binding site and a potentially reactive group have been prepared as models for enzyme active sites (79PAC979, B-82MI52100). 

Stereocontrolled syntheses of macrolides and macrolactams are well developed. Much remains to be done toward the efficient enantioselective construction of five and suc-membered cyclic ethers and amines. Four recent natural product syntheses illustrate the current state of the art. 

C-Glycosyl compounds have a carbon atom in place of the exocyclic oxygen atom of the acetal group and, therefore, are branched cyclic ethers. An example is the naturally occurring anthroquinone dye, caoninic acid [1260-17-9] (Cl Natural Red 4). 

Viewed (and drawn) in a terpene-like perspective, C-glycosyl compounds are in fact functionalized tetrahydrofurans and tetrahydropyrans. As such, they can be considered as versatile chirons for the synthesis of a variety of natural products containing cyclic ether motifs, such as in the ionophores. 

With complex (102) as catalyst, reaction (107) has been used to prepare a precursor of the natural product curvularin.482 If cyclic ethers are used instead of alcohols, w-haloesters are... 

Table 6.5 lists the different thermal property measurements that have been performed on hydrates of cyclic ethers, other nonnatural gas components, and natural gas components. 

The equilibrium position and subsequent rate of ring-opening differed significantly with the nature of the cyclic ether monomer. For example, the monomers, PO and oxetane, which have similar steric requirements and significantly different pKb values (6.94 and 3.13, respectively) [63], would be expected to bind to the metal center quite differently. As shown in Scheme 8.8, solution IR spectroscopy revealed that, in the presence of a large excess of oxetane monomer, the (salen)Cr(N3)2 species existed as an equilibrium mixture, greatly favoring the neutral oxetane-bound species [39]. 

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