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Synthesis of Limonoid and Steroidal intermediates

University of British Columbia

The cyclopentyl intermediate 4 is an easily obtained, highly enantiopure starting material for the synthesis of numerous triterpenoids. Prepared from (+)-endo-3-bromocamphor (2) in a four-step sequence, 4 has been converted into two advanced triterpenoid intermediates. In an eleven-step sequence 4 was transformed into the bicyclic intermediate (42) that could be used in an enantiospecific approach to the limonoids. The enone 42 was subsequently dialkylated in a regio- and stereoselective manner to produce the intermediate 45. Removal of the silyl protecting group followed by oxidation and acid-catalysed annulation produced the tricyclic enone 53. Structure 53 represents a highly advanced ent-limonoid intermediate with correct relative and absolute stereochemistry with obvious similarities to limonoids such as ent-azadirone (6). Further investigations illustrated 4's utility in the synthesis of the steroidal hydrindane system. Using an analogous pathway 4 was again converted to a bicyclic enone 104 in eight steps. Regiospecific alkylation followed by medium pressure hydrogenation and epimerization yielded the hydrindane 110. Extensive NMR analysis of this compound was used to provide conclusive evidence of 110's absolute stereochemistry. This route is therefore potentially useful in an approach to natural products such as 1α, 25-Dihydroxyvitamin D₃ (58).

Thesis/Dissertation

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2008-08-20

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http://hdl.handle.net/2429/1430

Chemistry

University of British Columbia

UBCV

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