Heptaenes

This group contains over 30 described members, including two of clinical impor tance, amphotericin B and candicidin. Heptaenes can be divided into three subgroups on the basis of the presence or absence of an aromatic sidechain. 

The heptaenes of the candicidin group [61 ], candicidin, hamycin and ascosin, contain an aromatic sidechain (3) derived fromp-aminoacetophenone [9,34,35]. 

The third group, which includes perimycin and candimycin, also possesses an aromatic sidechain but in this-case it is A -methylated as in formula (4) [63]. Perimycin also contains a unique amino sugar, perosamine (2) [31]. 

Carbonyl pentaenes 364 (single broad peak) Flavomycoln 25 

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Fig. 9.3. (A) Carbon framework from X-ray crystal stmcture of iyn-tricyclo[8.4.1.1]hexadeca-1,3,5,7,9,11,13-heptaene. (B) Side view showing deviation from planarity of aimulene ring. (Reproduced from Ref 60 by permission from the International Union of Crystallography.)...

Fig. 9.4. (A) X-ray crystal structure of j> n-tricyclo[8.4.1.F ]hexadeca-2,4,6,8,10,12,14-heptaene. iB) X-ray crystal structure of anti stereoisomer of tricyclo[8.4.1.1 ]hexadeca-2,4,6,8,10,12,14-heptaene-5-carboxylic acid. (Reproduced from Ref 63 by permission of Wiley-VCH.)...

Therapeutic Function Topical antifungal Chemical Name Heptaene macrolide antibiotic Common Name —... 

Scheme 38 Regioselective RCM of heptaene 193 in Maleczka s synthesis of the structure 195 proposed for amphidinolide A [96a]...

In addition it is probable that each absorbance has a shoulder on the short wavelength side of the maximum. Application of Sorenson s data would associate the peaks at 590, 660, 730 and 790 nm with ions derived from pentaenes, hexaenes, heptaenes and octaenes respectively and interconversion of A qq to A660 A,q t0 A730 so on corresPonds to an increase In the length of tne ions by one unit in each case. Wasseiman (41) has also studied polyenic cations derived by protonation oF various polyenes but the reliability of his spectral data has been questioned (40) due to the high reactivity of the species concerned. 

In contrast to 2-cyclohexenones where no a-cleavage is observed this reaction occurs efficiently for 2,4-cyclohexadienones 216,217). Among different synthetic applications the synthesis of dimethylcrocetine (a heptaene dicarb-oxylic acid) may serve as an illustration (2.11) 218),... 

Sowinski and coworkers40 reported a structure of vacidin A (63), an aromatic hep-taene macrolide antibiotic. The constitution of vacidin A, a representative of the aromatic heptaene macrolide antibiotics, was established on the basis of 13C and H- H double quantum filtered correlated spectroscopy, rotating frame nuclear Overhauser effect spectroscopy, 7-resolved 11 as well as H-13C correlation NMR spectra. The geometry of the polyene chromophore was determined as 22E, 24E, 26E, 28Z, 30Z, 32E, 34E. 

Perhaps the best known clinical agent is the heptaene polyene, amphotericin B 50, isolated from Streptomyces nodosus and first reported in 1956. The full structure was not elucidated until 1970 when it was determined by X-ray crystallography,56 closely followed by a description of the absolute configuration determined by utilising the iodo-derivative for X-ray and by mass spectroscopy.57 Quite recently, 50 years after its initial discovery, a full review giving the highlights of the chemistry around the compound was published by Cereghetti and Carreira.58... 

Amphotericin B is an amphoteric heptaene maaolide with antifungal achvity. Conventional amphotericin B for injection contains amphotericin B, sodium deoxycholate, and sodium phosphates. The drug product must be reconshtuted with water for... 

Figure 4. Proposed partial model for the AmB-induced pore in the cell membrane. The drug acts as a counterfeit phospholipid, with the C,j hydroxyl, C,g carboxyl, and C g mycosamine groups situated at the membrane-water interface, and the Cj to and C gto chains aligned in parallel within the membrane. The heptaene chain will seek a hydrophobic envi-ronmentwhile the hydroxyl groups will seek a hydrophilic environment Thus, a cylindrical pore will be formed, the inner watt of which consists of the hydroxyl-substituted carbon chains of the AmB molecules, and outer watt of which is formed by the heptaene chains of the molecules and by sterol nuclei.

Polyene antibiotics, such as amphotericin B (II) which contains seven conjugated double bonds (heptaene moiety), are subject to attack by peroxyl radicals, leading to aggregation and loss of activity. ... 

Pattenden has described the reduction of a triene selenyl ester, RCOSeR, by a cascade sequence to give a tetracyclic steroidal ketone,157 and of an acyclic heptaene selenyl ester, by a seven-fold cascade of ring closures to give a heptacyclic system.158... 

The biogenesis of the polyene MACROLIDE candicidin (a heptaene) is mostly from acetate and propionate with the additional presence in the structure of p-am1noacetophenone and mycosamine (3-ami no-3,6-dideoxy D-mannopyranose) 43. The biosynthesis of the candidin and candihexin complexes (heptaene and hexaene, respectively) seems to be via sugar-free aglycones which are within the producing mycelium. Glycosylation may take place during secretion of the final products. 

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