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Further investigations on the use of Camphor as an Enantiopure starting material in natural product synthesis

University of British Columbia

The use of (-)-camphor (ent-9) as an enantiopure intermediate in pseudoguaianolide and limonoid synthesis and further aspects of the chemistry df 4-methylcamphor (87) are presented in this thesis. First, the preparation of relay compounds ketal-enone 140, hydroxy-ketone 123, hydroxy-enone 158, and hydroxy-ketone 128 represents a formal, enantiospecific synthesis of the helenanolides carpesiolin (96), helenalin (95), bigelovin (97), mexicanin I (98), and linifolin A (99) and the ambrosanolides damsin (102) and confertin (103). (-)-Camphor (ent-9) was converted in nine steps to ketal-ester 164b. Stereoselective alkylation of 164b with methyl iodide yielded ketal-ester 165 that could be elaborated to the ketal-enone 140 in seven steps. Hydroxy-ketone 123 was obtained from 140 in a further three steps. Similarly, stereoselective alkylation of 164b with allyl bromide yielded ketal-ester 184 that could be converted subsequently to hydroxy-enone 158 in nine steps. Finally, catalytic hydrogenation of 158 provided hydroxy-ketone 128. Secondly, as part of an enantiospecific synthetic approach to the limonoids, the tricyclic enone 257 was prepared. (-)-Camphor (ent-9) was converted to the known bicyclic enone-ester (ent-255) in ten steps. Alkylation of ketal-ester .262, derived from ent-255, with methyl bromoacetate yielded ketal-diester 263, which could be transformed into dimethoxy-enone 267 in three steps. Two successive alkylations of enone 267 yielded the j3,^unsaturated enone 279, and subsequent desilylation, oxidation, and aldol condensation steps provided the tricyclic enone 257, which has potential as a BCD-intermediate for the synthesis of tetracyclic limonoids. Finally, a proposed mechanism for the bromination of endo-3-bromo-4-methylcamphor (327) to yield e«do-3,9-dibromo-4-(bromomethyl)camphor (332) was evaluated using the corresponding deuterium-labelled analogue, e«do-3-bromo-9-deuterio-4-(deuteriomethyl)camphor (351), as substrate. NMR spectroscopic evidence was used to identify the product resulting from the bromination of 351 as g«rfo-3,9-dibromo-9-deuterio-4-(bromodeuteriomethyl)camphor (352). Evidence supporting the proposed existence of unsaturated intermediates 355 and 358 in the bromination mechanism was also obtained.

Thesis/Dissertation

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2009-03-17

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http://hdl.handle.net/2429/6184

Chemistry

University of British Columbia

UBCV

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