Fission of Ring

Kubota and co-workers describe a novel oxidative rearrangement of the diosphenol (58) of 17iS-hydroxyandrost-4-ene-2,3-dione to the A-nor-A -1,2-diketone (59) in 33 % yield by the action of specially prep d manganese dioxide in boiling acetone. The rate of ring contraction is very sensitive to the source of the oxidant, and a trace of dilute sulfuric acid in the reaction mixture causes oxidative fission of ring A. 

It is noteworthy that, in all the many Hofmann degradations involving an Na quaternary metho salt, fission of ring III has never been observed. 

After irradiation, the steroid undergoes fission of ring B therefore, it is known as a. secosteroid. This is indicated in the name by the "9.10-seto" portion. The "ergosta portion indicates the presence of 28 atoms in the carbon. skeleton. 

A new and very neat synthesis of evodiamine and rutaecarpine is described by the authors as a retro mass spectral synthesis , since the original conception was derived from the mode of fragmentation of these alkaloids in the mass spectrometer this involves a familiar retro Diels-Alder fission of ring c. Evodiamine (16a) was thus constructed by a 27r + 47r cycloaddition of 3,4-dihydro-/8-carboline with the keteneimine (17), prepared in situ by elimination of sulphur dioxide from the sulphinamide anhydride (18) (Scheme 7). When the anthranilic acid derivative (19) was used the product was rutaecarpine (20) itself, the initially formed dihydro-... 

Although not strictly a rearrangement reaction, the behavior of (-)-vincadifformine (76) when heated in a sealed tube in a microwave oven is of interest. Almost quantitative racemization occurs, presumably via reversible Diels-Alder fission of ring C and the related achiral secodine intermediate (211). 

The mass spectrum of (6) contains,as expected, a major fragment at m/e 197. Deuteriation experiments unexpectedly show, however, that only ca. 20% of this ion originates via a retro-Diels-Alder fission of ring d instead, the ion appears to be mainly the result of a stepwise fragmentation of ring D (Scheme 4). 

A variety of methods have been employed in the fission of rings E and F. Among the more successful approaches have been (a) alkoxylating fission, (b) reductive fission, (c) cyanogen bromide, and (d) fission by the Hofmann method. 

The 16-aminomethyleneandrostan-17-one (447) was not hydrolysed by acids to the expected keto-aldehyde, but instead gave the bis-steroidal amine (448). The pyrrolidino-derivative (449), however, reacted with hydrochloric acid in acetone by fission of ring D (450) to give the 16,17-seco-eniminium salt (451), further hydrolysis of which afforded the carboxy-aldehyde (452). ... 

The structure proposed earlier for catharinine (vinamidine) has now been shown to be incorrect catharinine is, in fact, a product of the fission of ring D in leurosine or vinblastine, but in a different sense from that postulated earlier. The structure of catharinine (247) was established by the X-ray crystal structure analysis of the non-vindoline component (248), obtained by the reductive cleavage of catharinine in acid solution. A plausible biogenetic derivation of catharinine from leurosine (249) is illustrated in Scheme 41. 

The synthesis of Catharine (250), " to which catharinine was initially believed to be closely related, has in fact been achieved by a process which involves the fission of ring D of the velbanamine component of leurosine (249). This conversion was first reported as a result of the accidental over-oxidation that occurred in the preparation of leurosine from anhydrovinblastine by means of t-butyl hydroperoxide in the presence of trifluoroacetic acid. The by-product in this reaction was initially regarded as the 21-lactam related to leurosine, but it has now been recognised as Catharine, and can be prepared equally well by oxidation in the absence of acid (Scheme 41) a radical mechanism appears to be involved. In view of this facile conversion under oxidising conditions, the status of Catharine as a bona fide natural product is open to question. Indeed, the status of leurosine itself as an alkaloid has been questioned, in view of the ease with which anhydrovinblastine is oxidised to leurosine, even in the absence of specific oxidising agents. For example, anhydrovinblastine is oxidised to leurosine if not stored in an inert atmosphere, and the conversion is even more rapid in solution, particularly in the presence of adsorbents such as silica or alumina. A conversion of 40% has been observed after only 72 hours at room temperature. In view of these results it is perhaps not surprising that anhydrovinblastine has not been isolated from any Catharanthus species examined to date. 

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