Polyene addition

Addition of sterol to bilayer membranes dramatically decreased both ionic and non-ionic permeability [212] but interaction of polyenes with membrane sterol did more than simply reverse the effect of sterol incorporation. Polyene addition produced specific permeability alterations [201—205] consistent with the creation of ion-selective channels or pores within the bilayer. 

Whether phase transition changes are directly responsible for the permeability changes observed in liposomes and bilayers is debatable but results obtained by DSC are indicative that polyene addition to sterol-containing liposomes, bilayers or membranes markedly alters the molecular structure of the membrane by reducing the phospholipid-sterol interaction. Such alterations may be the basis for the observed polyene-mediated permeability changes to ions and small nonelectrolytes [ 101,103-106,201 -212,216]. 

Other, removable cation-stabilizing auxiliaries have been investigated for polyene cyclizations. For example, a sdyl-assisted carbocation cyclization has been used in an efficient total synthesis of lanosterol. The key step, treatment of (257) with methyl aluminum chloride in methylene chloride at —78° C, followed by acylation and chromatographic separation, affords (258) in 55% yield (two steps). When this cyclization was attempted on similar compounds that did not contain the C7P-silicon substituent, no tetracycHc products were observed. Steroid (258) is converted to lanosterol (77) in three additional chemical steps (225). 

Amphotericin B. Amphotericin B (3), an important polyene antibiotic, is administered almost exclusively via the intravenous route and is therefore discussed in more detail under the systemic antimycotics. The vaginal tablets contain 50 mg amphotericin B, and 100 mg tetracycline base per tablet (see also Antibiotics, tetracyclines). The tablets for oral use contain 50 mg amphotericin B, 250 mg tetracycline base, and 125 mg sodium hexametaphosphate. A combination ointment contains 1 mg fludrocortisone acetate, 2.5 mg neomycin, 0.25 mg gramicidin, and 1 g plastibase in addition to 30 mg amphotericin B (see also Antibiotics, peptides). 

The rectangular structure is calculated to be strongly destabilized (antiaromatic) with respect to a polyene model. With 6-3IG calculations, for example, cyclobutadiene is found to have a negative resonance energy of—54.7 kcal/mol, relative to 1,3-butadiene. In addition, 30.7 kcal of strain is found, giving a total destabilization of 85.4 kcal/mol. G2 and MP4/G-31(d,p) calculations arrive at an antiaromatic destabilization energy of about 42kcal/mol. ... 

The fulvalene systems are not predieted to be aromatie by any of the theoretieal estimates of stability. Even simple resonanee eonsiderations would suggest polyene behavior, sinee only dipolar resonance stmctures can be drawn in addition to the single nonpolar stmeture. 

Head-to-head units formed in a molecule have not only been considered as initiation sites for the dehydrochlorination but also as termination points for the growing polyene sequences [19,66,68]. Head-to-head units can either be formed through termination by combination [Eq. (19)] or by head-to-head addition during propagation [Eq. (20)]. 

In the stabilization of PVC, the principal mode of action of the various stabilizer systems has been explained in terms of the Frye and Horst mechanism, i.e., substitution of labile chlorines by more stable groups. Evidence for other actions, such as HCl neutralization, addition to polyene sequences, and bimetallic complex formation have also been given. Despite the wide acceptance of the Frye and Horst mechanism, researchers have frequently contended that this could not be the dominant mechanism in the stabilization of PVC. 

Additions of sulfinic acids to polyenes ( hydrosulfonylation ), however, proceed with very strong acids80 or under catalysis of Pd complexes81 (equation 17). With copper(II) arenesulfinates, azulene has been oxidatively sulfonylated in the 1- and 2-positions of the five-membered ring82 (equation 18). The sulfonylmercuration has also been applied with success to conjugated dienes83 (equation 19). 

The Ramberg-Backlund reaction has been utilized for the preparation of polyenes. 1,3-Butadienyl allyl sulfones 398 and 399 were transformed into the tri- and tetra-enes 400 and 401 by alkylcuprate addition and the Ramberg-Backlund-type S02 extrusion449. Julia and coworkers450 carried out the Michael addition of various nucleophiles such as ethanol, t-butyl acetoacetate and phenyl thioacetone to allyl dienyl sulfones 402 and then converted them to diallyl sulfones 403. The sulfones were transformed into isoprenoid, 404 by the Ramberg-Backlund reaction. 

Addition — The addition of a radical species such as a peroxy radical ROO or the hydroxyl radical HO" to the polyene chain could generate a carotenoid-adduct radical CAR + ROO —> CAR - OOR. 

As with carbocation-initiated polyene cyclizations, radical cyclizations can proceed through several successive steps if the steric and electronic properties of the reactant provide potential reaction sites. Cyclization may be followed by a second intramolecular step or by an intermolecular addition or alkylation. Intermediate radicals can be constructed so that hydrogen atom transfer can occur as part of the overall process. For example, 2-bromohexenes having radical stabilizing substituents at C(6) can undergo cyclization after a hydrogen atom transfer step.348... 

Besides taxodione and taxodone, these synthetic approaches have been conveniently modified to synthesize other related derivatives such as ferruginols, sugiols, and royleanones.51-52,56-57,60-62 In addition, the enantiomeric-selective synthesis of (+ )-taxodione 1 has been reported using (—)-abietic acid as the starting material63 or with a chiral ligand in the polyene cyclization process.64... 

In addition, the results indicated that the efficiency of cis —> trans increased as the initial cis double bond configuration is shifted from the center of the polyenic chain, consistent with the 7j, triplet excited state potential curve that has a very shallow minimum at the 15-cis position compared to the deep minima at the all-trans position. The results strongly suggest that isomerization takes place via the 7j state of the carotenoid even in the case of direct photoexcitation, with their photosensitized process because of the very low intersystem crossing quantum yield, isc ([Pg.246]

Solvents, Additives, and Extraneous Impurities. The rate of PVC photodegradation under air at wavelengths >250 nm is said to be increased by small amounts of residual tetrahydrofuran (THF) or dichloroethane (56). On the other hand, residual THF has been reported not to enhance the dehydrochlorination of the polymer during irradiation under nitrogen at X >240 nm (41). Nevertheless, under the conditions of the latter study, THF was found to Increase the relative concentrations of the shorter polyene products (41). This effect was attributed to a facile... 

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