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Total synthesis of steroidal derivatives : synthesis of hydrochrysene analogues and related compounds.

University of British Columbia

A sequence leading to the total synthesis of cis-syn-cis-dodecahydrochrysene and cis-octahydrochrysene derivatives is described. The synthesis employs the Robinson-Mannich base reaction and the Michael reaction to construct the tetracyclic skeleton. Condensation of 6-methoxy-2-tetralone with 1-diethylamino-3-pentanone methiodide affords an isomeric mixture of tricyclic ketones. This mixture is then condensed with methyl vinyl ketone to yield 1β,6-dimethyl-6-hydroxy-2,3-(2'-methoxy-7',8'-dihydro-6',5'-naphtho)-Δ² -bicyclo [3.3. 1] nonene-9-one (IV). By appropriate modifications this compound can then be utilized for the synthesis of a variety of hydrochrysene analogues. Oxidation of dodecahydrochrysenes with t-butyl chromate solution is found to be dependent on the stereochemistry of the molecule. Whereas trans-anti-trans-2-methoxy-8β -acetoxy-10a-methyl-4b, 5,6,6a, 7,8,9,10,10a,10b,11,12-dodecahydrochrysene (XVIII) gives the 12-keto derivative XIX, cis-syn-cis-2-methoxy-8α-acetoxy-10a-methyl-4b,5,6,6a,7,8,9,10,10a,10b,11,12-dodecahydrochrysene (XVII) yields cis-2-methoxy-8α -acetoxy-5-keto-10a-methyl-5,6,6a, 7,8,9,10,10a-octahydrochrysene (XXIV). In the latter reaction, t-butyl chromate is superior to chromium trioxide as an oxidizing agent. Nuclear magnetic resonance spectra are found to be invaluable for the purpose of characterization of these rather complex molecules.

Text

2011-10-31

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http://hdl.handle.net/2429/38436

Chemistry

University of British Columbia

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