9,10-Dihydrophenanthrenes structures

The most famous of these compounds is combretastatin A-4 (CA-4,7), isolated by Pettit et al. in 1989 [30]. Pettit s research led to the isolation and structural determination of a series of phenanthrenes, dihydrophenanthrene, stilbene, and bibenzyl compounds [31]. CA-4 (7), alongside CA-1 (8), was found to be an extremely active inhibitor of tubulin polymerization [30,32]. The major problems associated with these compounds were poor bioavailability and low aqueous solubility [33,34], and hence, research in the field was turned to designing better alternatives with the hope of eradicating the negative properties of these potent compounds. 

The partially hydrogenated ring of dihydtocorannulene constitutes a 1,3-cyclo-hexadiene ring, a system that has been well-studied with respect to its geometry and the conformational preferences of substituents. However, the curvature of the corannulene surface introduces an additional stereochemical factor that makes the conformational analysis especially interesting. 1,3-Cyclohexadiene (23) and 9,10-dihydrophenanthrene (24) serve as models they are structurally similar systems, and their stereochemistry and conformational preferences are well documented in the literature. In both cases, the reduced ring adopts a nonplanar, semi-chair conformation of symmetry. 

There are two types of enamides readily available for the simple synthesis of protoberberine alkaloids via the route involving photocyclization. One is the 2-acyl-1-benzylideneisoqui noline-type enamide that has a stilbene structure in the molecule and is known to undergo a six -electron conrota-tory electrocyclic cyclization to a dihydrophenanthrene and subsequent dehydrogenation (103), and thus provides a useful synthetic route to apor-phine alkaloids. The second is the 2-aroyl-l-methyleneisoqui noline-type enamide that gives the 8-oxoberbine in good yields on irradiation. 

Fluorene has been reported to afford the 3,9a-dihydro product, but it is almost certain that this is the 2,4a-dihydro isomer (55 = 1) by analogy with biphenyl. 9,10-Dihydrophenanthrene (56) is reduced as expected to (55 n = 2), but spontaneously reverts to the starting material on standing. These systems do not require the presence of alcohol for reduction and it is consequently possible to alkylate the intermediate anions with alkyl halides, as (56) gives (57). These products are much more stable and structural analysis is simplified accordingly oxidation of the doubly allylic methylene occurs readily to afford the dienone (58 Scheme 7). Dienones of this type have potential as intermediates for the synthesis of natural products. Anthracene and phenanthrene are both readily reduced in the central ring to form the 9,10-di-hydro derivatives as might be expected, but to avoid further reduction it is necessary to have an iron salt present. Further examples are reviewed elsewhere. ... 

The stilbene-dihydrophenanthrene photocycllsatlon reaction continues to find synthetic applications. The tetra-oxygenated methyl phenanthrene skeleton (161) has been prepared by photocyclisation of the stilbene (162) aromatisation of the intermediate dihydrophenanthrene occurs by elimination of methanol. 2 nq photocyclisation was observed In the absence of the cyano group in this compound 2 although the closely related structures (163) and (164) are said to cyclise to the phenanthrenes (165) and (166). Triarylethylenes are important... 

Substituted di- and triphenylamines lead to carbazoles (XXII, 0, Y = NR Table 7, number 8). The yields are poor, however, and the cyclization is restricted to tertiary amines with the para position blocked by substituents not susceptible to substitution or elimination. The 2-methyltetramethoxybibenzyl derivative XXIII cyclizes in an anodic 2,6 -coupling reaction, with a subsequent dienone-phenol rearrangement, to give an 88-98% yield of the dihydrophenanthrene XXIV [Eq. (15)], which contains the essential structural elements of the B, C, and D ring of steroids [143]. 

Phenanthrenoids are structurally classified into 5 subclasses, namely, phenanthrenes, 9,10-dihydrophenanthrenes, dimeric phenanthrenoids, phenanthrene alkaloids and other phenanthrenoids. 

Three novel phenanthrenes have been isolated from the wetland plant Juncus acutus. The structures of the novel phenanthrenes were established as 2-hydroxy-l,6-dimethyl-5-vinyl-phenanthrene (320), 2,7-dimethoxy-l,6-dimethyl-5-vinylphenanthrene (321) and 2-hydroxy-6-hydroxymethyl-l-methyl-5-vinyl-phenanthrene (322) [164, 165]. In spite of the great number of 9,10-dihydrophenanthrenes, only quite a small number of phenanthrenes have been reported until now as constituents of Juncaceae. 

Three new dihydrophenanthrenes, stemanthrenes A-C (356-358), along with the above mentioned bibenzyls (133, 135, 136 and 138) were isolated and identified from the underground parts of Stemona cf. pierrei. The structures showed a common substitution pattern for aromatic ring A and characteristic C-methylations for ring B. The trivial name, racemosol, for ring B was redefined to stemanthrene D (359) due to its priority for another compound [76]. 

Intramolecular photo-induced cyclization between aryl and ethylene moieties is a common reaction observed for a variety of molecular structures. The formation of 9,10-dihydrophenanthrene... 

If a stilbene is constrained in a cis configuration, for example when the double bond is part of a small ring, the photo-cyclisation to a dihydrophenanthrene is normally very efficient. Fields has reported that diphenylmaleic anhydride photocyclises readily to the phenanthrene (199), and this corrects an earlier report which assigned the structure of the product as a 2+2 dimer. 

It will be noticed that in four of the five structures the link between carbon atoms 9 and io is double these atoms are therefore the most reactive. Hydrogenation produces 9, io-dihydrophenanthrene XXIV. This com-... 

Aryl groups attached to adjacent positions on heterocyclic rings frequently photocyclise to dihydrophenanthrenes readily. Thus the reaction has been reported to proceed smoothly for (165), (166), (167),and (168), although it fails for the sulphur analogue of (168), compound (169). Heterocyclic arenes linked by an ethylene also photocyclise and new examples of structures which do this are (170), ° (171), (172), (173),(174), (175) and (176). An example has also been published of a l-aryl-2-heteroarylethylene possessing structure (177) which cyclises to (178) in the presence of oxygen as the oxidant. ... 

In a reaction which is mechanistically related to the stilbene-dihydrophenanthrene photocyclisation, the anilide derivative of (178), compound (179), photocyclises to give (180). As mentioned in the Introduction to this chapter, such enamide cyclisatlons have now been reviewed. Other new examples of this reaction are the formation of (181) from (182) and the formation of the regioisomers (183) and (184) from (185) by irradiation of the enamldes in the presence of sodium borohydride. These enamide photocyclisation reactions can be viewed as an electrocyclic closure of the amide contributing structure (186) to give (187) in the presence of borohydride the iminlum function in (187) is reduced to the observed products. 

Thus, it was logical to combine the principle for preparation of "step-ladder" structures with new, efficient and selective methods for aryl-aryl coupling. A first attempt at this was from Yamamoto et al. [17]. They coupled 2,7-dibromo-9,10-dihy-drophenanthrene to give an ethano-bridged poly( arflf-phenylene) derivative (poly(9,10-dihydrophenanthrene-2,7-diyl)) (fi) by way of low-valent nickel complexes, which were used either stoichiometrically as reagent (Ni(COD)2) or were genera-... 

Other studies of material extracted from high-volatile bituminous coal (in the presence of hydrogen at dSO C [SdO F]) indicate the occurrence of dihydrophenanthrene units in the extract and, therefore (by extrapolation and inference), in the coal. This, of course, is analogous to the earlier postulate of such units as an integral part of the structure of coal. 

The enzymatic mechanisms for lengthening of the side chain of cinnamic acids by one or more C2 units followed by cycli-zation are widespread in higher plants. Although by far the largest group of compounds formed by this route is the flavo-noids, several other important structural entities are known to arise in this manner. Among these are the 2-pyrones, stilbenes, dihydrophenanthrenes, and xanthones. 

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