Isocyclic ring

An alternative route to the reaction sequence applied by Woodward for the formation of the isocyclic ring E of chlorophyll a in his synthesis has been developed.40 55,56 It was shown that... 

The typical isocyclic ring E present in chlorophylls is susceptible to a number of different modifications such as epimerization, which produces stereoisomers by inversion of the configuration at C-13 of their parent pigments. These 13 -epichlorophylls, known as chlorophylls a and b, are minor pigments. They are considered artifacts produced in the course of handling plant extracts and sometimes are also found in small amounts in heated and deep-frozen vegetables, hi the old Fischer systan of nomenclature that can still be found in some literature, these epimers were named 10-epichlorophylls. 

Esterification of the propionic acid side chain at C-13 (ring C) with a methyl group catalyzed by S-adenosyl-L-methionine-magnesium protoporphyrin 0-meth-yltransferase yields protoporphyrin IX monomethyl ester (MPE), which originates protochlorophyllide by a P-oxidation and cyclization of the methylated propionic side chain. This molecule contains a fifth isocyclic ring (ring E), the cyclopentanone ring that characterizes aU chlorophylls. 

Another heterocyclic compound obtainable in considerable quantities-quin-oline-nitrates in the isocyclic ring. Indole Mid carbazole behave in a similar way. Nitro derivatives of these compounds have not yet found practical application. 

The basic structure of Chls is the tetrapyrrolic porphyrin macrocycle with an attached isocyclic ring (Fig. 1). This structure has been termed phytoporphyrin by the lUPAC commission (2). The four nitrogens bind a magnesium ion (Mg +) as central... 

Several functional groups of Chls are reactive. The allylic long-chain esterifying alcohol, phytol, is readily hydrolyzed. Under alkaline conditions, or with bases, the isocyclic ring is modified extensively, and it is often opened. The macrocycle can be opened (photo)chemically at the methine bridges, and it is cleaved enzymatically at C-5 (14,15) during Chi degradation. 

The best source for Chi a is the cyanobacterium Spirulina platensis, which is available commercially. Chi a/b mixtures can be obtained from all green plants. All other Chls are less readily accessible, which limits their applications. Several Chi derivatives are used as dyes for food colorants (Cu-chlorophyllin) and cosmetics. The chlorophyll used for the latter is a complex mixture of degradation products. More recently, (B)Chl derivatives have gained increasing interest as photosensitizers in photodynamic therapy of cancer, these compounds include pigments in which the isocyclic ring is opened and/or the central metal has been removed or replaced (e.g., by Pd" " ) to increase phototoxcicity (12, 13). 

Only fusion of heterocyclic rings to the 2,3-position proved to be a useful extension of the steroidal nucleus to produce enhanced activity or better dissociation of androgenic-anabolic activity. Isocyclic ring extensions and fusion of a heterocyclic ring to other positions, such as 1,2 (D-98) or 16,17 (E-27,E-31), gave products with decreased or abolished activities. 

In addition to the skeletal modifications accomplished by replacement of one carbon atom, several attempts have been made to improve hormonal activity by replacement of a whole isocyclic ring by a heterocyclic ring. The isocyclic ring A was replaced by a pyrazole [211], isoxazoline [212], pyrimidine [213], or thiopyrimidine [214] ring however, all these types of compounds were inactive. In view of the fact that fusion of the same heterocyclic rings in addition to the steroid nucleus led to highly active compounds, this finding emphasizes the importance of the steroid skeleton. 

In complete contrast to metalloporphyrins, the analogous metallochlorins showed no attractive interactions whatsoever. An important assembly occurred in the case where the keto oxygen of the isocyclic ring in chlorophylls bound to the central magnesium ion of another molecule. Dimers with an interplanar separation of 4.2. 7 A were formed. A series of earlier papers handled the characterization of such dimers by H-NMR and IR spectrosco-pies o ei, their behaviour has been compared with covalently connected dimer... 

The hydrolysis of the methyl ester and cleavage of the isocyclic ring in stronger alkalis... 

This compound, tentatively 9-oxy-deoxo-mesopyropheophorbide-a, is of interest as it offers a clue as to the mode of loss of the 9-ketone moiety inherited from chlorophyll-a. That is, it now appears that the 9-keto function is reduced to the alcohol which may then be dehydrated. If this were to occur, the product would contain a highly strained 6,Y-cycloetheno moiety. Most likely, concerted or subsequent and rapid reduction would follow and result in the common 6,Y-cycloethano type of isocyclic ring found in geoporphyrins of the DPEP-series. 

The oxidative scission of the isocyclic ring on the nucleus of chlorophyll and its derivatives, via allomerization, consists of a series of well documented reactions (6-7) and leads to such products as chlorin (e.g. -ea.-eg.-PeT nd purpurin (e.g. 

In the presence of oxygen, allomerization leads to the oxidative scission of the isocyclic ring. Products found in oxidative environments include the purpurin and chlorin acids (Figure 11). Tracing the down-hole fate of these compounds has proved futile, to date. That is, in cases were oxidation dominates, such as in sediments low in metabolizable organics (i.e. Philippine Sea. 

Figure 6.2.10 Circular dichroism spectrum of two diastereomers of a pheophorbide a dervative methoxylated at the isocyclic ring. (From Wolf et al.,1967.)...

Chlorophylls are key pigments participating in the absorption of light in photosynthesis. They consist of a magnesium porphyrin derivative in which one pyrrol ring is partially reduced. An isocyclic ring is also present Although no SERRS... 

The oxidative ring closure of a magnesium complex of porphyrin p-ketoesters (32a) onto the neighboring me.ro-position by iodine in methanol affords a meth-oxy phaeoporphyrin ester (33a) and provides a model for the biosynthesis of the isocyclic ring of chlorophyll. A more efficient process was the use of thallium... 

Several approaches have been made in the chlorophyll a molecule 15, by introducing a large number of metals," modification of the isocyclic ring, modification of the vinyl group at position 3, as well as by replacing the phytyl group at the propionyl residue throu either trans-esterification or conversion of the ester functionality into the corresponding amide derivatives (see Scheme 4, also see Chapter 1 by Smith). 

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