The Phenanthrenes

Opium is the dried, powdered sap of the unripe seed pod of Papaver somniferum, a poppy plant indigenous to Asia minor. Theophrastus described its medical properties in the third century BC, but the Sumerians, ca BC 4000, probably perceived its utility. Arab physicians knew of the dmg, and Arab traders carried it to the Orient where it was used as a treatment for dysentery. Paracelsus is credited with repopularizing the dmg in western Europe in the early sixteenth century by formulating opium into "laudanum", which is still in use. More than 20 different alkaloids (qv) of two different classes comprise 25% of the weight of dry opium. The benzylisoquinolines, characterized by papaverine [58-74-2] (1.0%), a smooth muscle relaxant, and noscapine [128-62-1] (6.0%), an antitussive agent, do not have any analgesic effects. The phenanthrenes, the second group, are the more common and include 10% morphine (1, = R = H), 0.5% codeine [76-57-3], C gH2 N03, (1, R = H, R = CH3), and 0.2 thebaine [115-37-7], C 2H2 N03, (2). 

The location of the nitrogen end of the ethanamine chain in the phenanthrene nucleus has been discussed recently by Holmes et and... 

Gulland and Robinson, having reviewed the evidence available regarding the structure of morphine and codeine, came to the conclusion that the data on which Pschorr s formula was based have been too lightly dismissed, and suggested that the ethanamine chain is associated with the phenanthrene skeleton by the bridge 8—15—13 (a) or 8—15—14 (b), of which they preferred (a). 

Considerable progress has also been made with the alternative line of work, the search for a synthetic analgesic as effective as morphine and without its disadvantages. The work of the American Committee has shown that it is possible to produce analgesics with a dibenzofuran or carbazole nucleus in place of the phenanthrene or phcnanthrylene oxide nucleus of morphine and it is stated that synthetic products with analgesic potency equal to that of codeine have been prepared. In the 1938 report moderate analgesic potency was recorded for preparation No. 421, 9-methyl-2-(l-hydroxy-3-diethylamino)-propylcarbazole at 10 mgm. by injection. 

Hexahydrobenzoyloxodedelphonine acetate (VI) was dehydrogenated by selenium at 330° and gave as chief product a hydrocarbon, b.p. 90°/0-02 mm., whose composition, ultra-violet absorption spectrum and chemical properties, so far as examined, indicate that it may be a bicyclopentenobenzene and therefore in a different category from the phenanthrene hydrocarbons yielded by the atisine group of bases. 

Photolysis at 254 nm, CH3OH, CH2CI2, phenanthrene, 51-84% yield. These conditions are selective for ally lie and benzylic alcohols. In the absence of the phenanthrene, TBDMS ethers are also cleaved. ... 

As has been described in Chapter 4, random copolymers of styrene (St) and 2-(acrylamido)-2-methylpropanesulfonic acid (AMPS) form a micelle-like microphase structure in aqueous solution [29]. The intramolecular hydrophobic aggregation of the St residues occurs when the St content in the copolymer is higher than ca. 50 mol%. When a small mole fraction of the phenanthrene (Phen) residues is covalently incorporated into such an amphiphilic polyelectrolyte, the Phen residues are hydrophobically encapsulated in the aggregate of the St residues. This kind of polymer system (poly(A/St/Phen), 29) can be prepared by free radical ter-polymerization of AMPS, St, and a small mole fraction of 9-vinylphenanthrene [119]. 

Rigid diphosphines have been used to enforce n-ans-geometries thus with the phenanthrene-derived diphosphine (Figure 3.49, R = Et) the complexes PdLCb and PtLCl2 have closely similar geometries (Pd-P 2.307 A, Pd-Cl 2.306 A, P-Pd-P 177.4° Pt-P 2.293 A, Pt-Cl 2.304 A, P-Pt-P 177.1°)... 

Adachi K, T Iwabuchi, H Sano, S Harayama (1999) Structure of the ring cleavage product of l-hydroxy-2-naphthoate, an intermediate of the phenanthrene-degradative pathway of Nocardioides sp. strain KP7. J Bacterial 181 757-763. 

White, J.D., Hrnciar, R, Stappendeck, F. (1997) Asymmetric Synthesis of (-F)-Morphine. The Phenanthrene Route Revisited. Journal of Organic Chemistry, 62, 5250-5251. 

The phenanthrene system appears to be no more easily cleaved than the naphthalene system however, ethyl anthracene is clearly destabilized significantly more than the other compounds in the table. The large decrease in bond-dissociation energy for the anthracene system is reflected in the increase by three to four orders of magnitude in the rate of scission at conversion temperatures, as shown in the table. 

The coal residue was separated into a THF-soluble fraction and a THF-insoluble residue. The wt % yields and atom % 2H compositions are given in Table I. The coal residue was 6 wt % soluble in tetrahydrofuran. The soluble fraction had 23 atom % 2H content. Evaluation of the 2H NMR data showed that 85 wt % of this fraction was derived from the coal and that its deuterium content was 10%. The chemically-bonded naphthalene-d8 content of the THF-soluble fraction, estimated from the 2H NMR data, was about 15 wt % or approximately 1 wt % of the coal. The insoluble residue had 6 atom % 2H content. This indicates that the residue contained approximately 1 wt % chemically-bonded naphthalene which was estimated from the difference in the atom % 2H content of the insoluble residue and recovered naphthalene-d8. This gives a total chemically-bonded naphthalene-d8 content of approximately 2 wt %. Similar results were obtained in extraction experiments made with phenanthrene (30), where it was found that 3-7 wt % of the phenanthrene was chemically linked to the coal product. 

The phenanthrene 1,2- and 3,4-diones are synthetically accessible from the related 8 phenols. Oxidation of 2-phenanthrol with either Fremy s salt ((KS0 )2N0) or phenylseleninic anhydride gave phenanthrene 1,2-dione directly (55). Unexpectedly, oxidation of 3-phenanthrol with (KSOg NO yielded 2,2-dihydroxybenz(e)indan-l,3-d-ione (Figure 10). However, phenanthrene 3,4-dione was readily obtained from 3-phenanthrol by Fieser s method entailing diazonium coupling, reduction, and oxidation of the resulting 4-amino-3-phen-anthrol with chromic acid (56). 

Figure 2. Log kQ versus AEdeioc/3 plots for the spontaneous hydrolysis of tetrahydroepoxides. Rates were measured at 25 °C in 1 9 dioxane.-t O, ionic strength 0.1 (NaC104) except in the case of the phenanthrene and naphthalene tetrahydroepoxides, whose rates were measured at 30 °C in 1 0, ionic strength 1.0 (KC1). (Adapted from Refs. 25, 26, and 27.)...

Most carcinogenic PAHs contain the phenanthrene grouping in them (see Figure 2) and there are two important areas in these molecules that are often referred to in studies of PAH carcinogenesis. 

A difference in reactivity was observed between the phenanthro[9,10-r]- and acenaphtho[l,2-c]-l,2,5-thiadiazole 1,1-dioxides 51 and 53 when treated with thiourea. The acenaphtho derivative 53 gave the expected addition product however, the phenanthro thiadiazole 51 was reduced to the thiadiazoline 1,1-dioxide 52 (Equation 2) <2004JP01091>. The difference in reactivity was attributed to the enhanced resonance stability offered by the phenanthrene group. 

The complexes Cr(CO)3L, with L = phenanthrene, naphthalene, or anthracene, are more active for diene hydrogenation than with L = substituted benzenes (see also Section VIII), and this is attributed to an easier displacement of the arene by the diene substrate, the phenanthrene type being asymmetrically bonded, having two longer and more readily cleaved chromium-carbon bonds (198, 199). 

Salutaridinol 7-0-acetyltransferase catalyzes the conversion of the phenanthrene alkaloid salutaridinol to salutaridinol-7-Oacetate, the immediate precursor of thebaine along the morphine biosynthetic pathway in P. somniferum (Fig. 10.7).26 Acetyl CoA-dependent acetyltransferases have an important role in plant alkaloid metabolism. They are involved in the synthesis of monoterpenoid indole alkaloids in medicinal plant species such as Rauwolfia serpentina. In this plant, the enzyme vinorine synthase transfers an acetyl group from acetyl CoA to 16-epi-vellosimine to form vinorine. This acetyl transfer is accompanied by a concomitant skeletal rearrangement from the sarpagan- to the ajmalan-type (reviewed in2). An acetyl CoA-dependent acetyltransferase also participates in vindoline biosynthesis in Catharanthus roseus, the source of the chemotherapeutic dimeric indole alkaloid vinblastine (reviewed in2). Acetyl CoA deacetylvindoline 4-O-acetyltransferase catalyzes the last step in vindoline biosynthesis. A cDNA encoding acetyl CoA deacetylvindoline 4-0-acetyltransferase was recently successfully isolated.27... 

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