Lycoricidine, carbocyclization

The synthetic plan for an antitumor alkaloid, lycoricidine 64, based on the Ferrier carbocyclization is shown in Scheme 12.18. The tricyclic phenanthridone skeleton was envisioned to be constructed by C—C bond formation between C-lOa and C-lOb by a transition metal-catalyzed sp -sp carbon coupling reaction. The C-ring 65 possessing an... 

The phenanthridone alkaloid, lycoricidine 64 fScheme 12.32). is known to possess cytotoxic activity. Based on the retrosynthetic analysis as discussed in Section 12.3.2 f Scheme 12.18T the Chida group reported the total synthesis of lycoricidine starting from d-glucose in which the Ferrier carbocyclization reaction was enployed as the key reaction. For the preparation of the cyclohexene unit in lycoricidine, d-glucose was converted into 2-azido-d-altropyranoside derivative 122 via epoxide 121 fScheme 12.31T Protection of the diol moiety in 122 afforded 68, which was transformed into 5-enopyranoside 67 by the action of DBU. Ferrier carbocyclization of 67 with 1 mol% of Hg(OCOCF3)2, followed by p-elimination,... 

Some natural products outside the carbohydrate field - particularly those with highly hydroxylated cyclohexane ring components - have been subject to synthetic studies which are dependent on the mercury-based rearrangement reaction the alkaloid (+)-lycoricidine (30) [12] and the cycloheptane-based (+)-calystegine 62(31) which stimulates growth of nitrogen-fixing Rhizobia [29] are examples, and compound 32 which offers novel access to the anthracyclinone components of anthracyclin anti-cancer compounds, has been produced by cycloaddition of a naphthalene-based o-xylylene to a 2,3-unsaturated hex-4-uloside followed by carbocyclization of the product by use of the mercuration procedure [30]. Studies on HMG-CoA reductase inhibitors like compactin have afforded the tetra-carbon-substituted 33 made from a hex-5-enopyranoside with deoxy-branch chains at C-2, C-3 and C-4 [31]. 

The Perrier reaction of 5,6-unsaturated hexopyranoses has been utilised on several occasions for preparing the carbocyclic analogues of lipid ring cleaved analogues, 82 and 83 of lycoricidine and narciclasine alkaloids, and the carba-sugars 84, which are related to allosamizoline. 

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