Polyene skeleton

To obtain high chemical yields and diastereoselectivities, it is necessary to introduce a removable cation-stabilizing group (R = Me2C=CH or F) in the proper position on the polyenic skeleton of 6.75 (Figure 6.64). As usual, the acetal auxiliary is cleaved by oxidation and -elimination ( 1.1.2). These cyclizations are carried out at low temperature (-40 to -90°C), and the Lews acid is either TiCl4/Ti(0/-Pr)4 or SnCl4. 

Carotenoids are CQnjugated polyenes (carotenes) or oxygenated derivatives (xan-thophylls, carotene acids) containing 40 carbon atoms or eight isoprene units (Table 5.2,1). The polyene skeletons are often symmetrical about the central 15,15 -bond (tail-to-tail arrangement). Prefixes in carotenoid names have the following signification ... 

Burke boronates can be hydrolyzed in situ under aqueous basic coupling conditions, as evidenced by fliis synthesis of the complex polyene skeleton of amphotericin B. 

It should be noted, on the other hand, that a symmetry reduction is predicted even in molecules II, VIII and XIII whose peripheral skeletons correspond to 4n-l-2 cyclic polyenes. The transannular bonds in these molecules are different in nature from those mentioned above. For example, the introduction of the transannular bonds between atoms 2 and 8 and between 3 and 7 of cyclododecapentaene to form bowtiene (II) (Fig. 3) brings about the splitting of the top filled degenerate orbitals of the unperturbed system into two levels, one with its energy raised and... 

Polyene cyclizations are of substantial value in the synthesis of polycyclic terpene natural products. These syntheses resemble the processes by which the polycyclic compounds are assembled in nature. The most dramatic example of biosynthesis of a polycyclic skeleton from a polyene intermediate is the conversion of squalene oxide to the steroid lanosterol. In the biological reaction, an enzyme not only to induces the cationic cyclization but also holds the substrate in a conformation corresponding to stereochemistry of the polycyclic product.17 In this case, the cyclization is terminated by a series of rearrangements. 

Scheme 10.1 gives some representative examples of laboratory syntheses involving polyene cyclization. The cyclization in Entry 1 is done in anhydrous formic acid and involves the formation of a symmetric tertiary allylic carbocation. The cyclization forms a six-membered ring by attack at the terminal carbon of the vinyl group. The bicyclic cation is captured as the formate ester. Entry 2 also involves initiation by a symmetric allylic cation. In this case, the triene unit cyclizes to a tricyclic ring system. Entry 3 results in the formation of the steroidal skeleton with termination by capture of the alkynyl group and formation of a ketone. The cyclization in Entry 4 is initiated by epoxide opening. 

Table 8 presents structures observed for monocyclic dienes and polyenes with rings large enough to accommodate trans C=C double bonds. In a cyclodecadiene molecule strain-free carbon skeletons can only be derived when two double bonds are diametrically placed and have the same configuration (as, cis or trans,trans). Cw,cis-Cyclodeca-1,6-diene (1,6-CDD) may exist in twelve different conformations, and it is therefore noteworthy that it almost exclusively prefers one of these, namely the one indicated in Table 8. This conformer does not have the repulsive transannular HH interactions that destabilize the corresponding saturated molecule in all conceivable conformers.

In related work, the Yamamoto group developed LBA 54 containing a pyrogallol skeleton for the enantioselective polyene cycHzations of 4-(homogeranyl)toluene and 2-geranylphenol derivatives (Scheme 5.70) [131],... 

Amphotericin B (AmB) is a polyenic macrolide used in fungal infections and leishmaniasis, despite severe side effects (Figure 4.60). Fluorination of the macrolide skeleton has been performed using Selectfluor for F NMR studies on the mechanism of ion-channel formation in membranes by amphotericin B. ... 

Fluorosulfuric acid is a widely used, highly effective reagent808 in electrophilic polyene cyclizations to synthesize fully cyclized compounds in a selective and stereospecific way. Furthermore, an internal nucleophile, most often oxygen, allows the construction of polycyclic skeletons with a heteroatom (vide supra). Snowden and co-workers809 transformed trienone 202 (a mixture of 4 diastereomers) into three isomeric irone derivatives [Eq. (5.293)]. Other acids gave inferior results. 

The question of aromaticity versus antiaromaticity and delocalized versus localized double bonds in pentalene (2) dates back to 1922, when Armit and Robinson compared it with naphthalene and postulated that the former might be similarly aromatic [32, 33]. While the first synthesis of a non-fused hexaphenylpentalene (38) [30] provided only some clues as to the non-aromatic reactivity of the pentalene skeleton, the tri-tert-butyl derivative 39, prepared and studied by Hafner et al. in great detail [31], gave a better insight. The ring-proton signals of this alkyl-substituted pentalene 39 are shifted upfield compared to those of fulvene (27) and other cyclic polyenes. This observation led to the conclusion that the pentalene derivative 39 should be an antiaromatic species. However, the results did not permit a distinction... 

Stereoselective synthesis of the C11-C16 fragment of the polyene macro-lide antibiotic, pentamycin, has also been accomplished under the aldolase protocol.45 A formyl and benzyl protected aldehyde, available from D-glucose by chemical methods, reacts with DHAP under the influence of FDP aldolase. After phosphatase hydrolysis the essential C11-C16 skeleton of pentamycin is generated. Removal of an additional hydroxyl group at position 1 and isolation of the C11-C16 fragment as a thioacetal, is accomplished in several steps (Scheme 5.23). 

First, we will take up cyclopropyl group formation by the rearrangement of carbon skeletons via cationic intermediates encountered in various mono- and sesquiterpenes, and also examine the illudin biosynthesis where contraction of a cyclobutyl cation to a cyclopropane has been invoked. We will then discuss the head-to-head condensation of isoprenoid alcohols at the C15 or C20 level to generate the cyclopropyl intermediates, presqualene pyrophosphate and prephytoene pyrophosphate, on the way to the C30 and C40 polyene hydrocarbons, squalene and phytoene respectively. Conversion of 2,3-oxidosqualene via common intermediate protosterol cation to cycloartenol or lanosterol represents an important pathway in which the angular methyl group participates in the three-membered ring formation. The cyclopropanation outcome of this process has been carefully studied. 

The reaction is very useful synthetically in the synthesis of polyenes, vitamins, fatty acids, and the annulenes. Baeyer used the reaction in his historic synthesis of indigo as long ago as 1882. The reaction allowed the unequivocal establishment of the carbon skeleton of this dye ... 

The pyropheophorbide skeleton bears a carotenoid polyene and a naphthoquinone derivative. The naphthoquinone is substituted with a bromine atom in order to increase its electron accepting abilities, and therefore the photoinitiated electron transfer rate from the tetrapyrrole. 

The next molecules to be discussed are the seven-membered monocyclic dienes and polyenes. i,3-Cycloheptadiene has been studied by GED (Table 7). The molecule has also been studied by MW. This study did not include a complete structure determination, but it was concluded that the carbon skeleton is planar, except for the carbon, corresponding to Cs symmetry. This is in agreement with the GED results. Ab initio calculation at the Mp2 level, utilizing the 6-3lG(d,p) basis set, has recently been carried out. Both the Cs and C2 conformers of 1,3-cycloheptadiene were considered, and the Mp3/6-3lG(d,p)//Mp2/6-3iG(d,p) calculations predict the Cs conformer to be 3.3 kJmol lower in energy than the C2 conformer. It was concluded that the calculated Cs conformer at the Mp2 level is in excellent agreement with the available MW and GED data. The Mp2 and Mp3 energetics results allow, however, for the possibility of the presence of a C2 conformer, as evidenced by NMR data. The experimental results do not rule out the presence of small amounts of a C2 conformer that is twisted about the diene region. 

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