Stereocontrolled Synthesis of Bicyclo[4.2.0]octadienes for SNF 4435 C and D Analogs, Bielschowskysin, and (+/-)-Kingianin A

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Authors
Kim, Keunsoo
Issue Date
1-Dec-12
Type
Dissertation
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en_US
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Abstract
Despite a growing interest in biological activities of natural products that contain the bicyclo[4.2.0]octadiene ring system such as SNF 4435 C and SNF 4435 D, an asymmetric version of 8??, 6?? electrocyclization has remained unattained. While investigating (2E,4Z,6Z,8E)-tetraene substrates bearing amide- or oxazoline-based chiral auxiliaries, a rationally designed chiral 4,5-trans-diphenyl oxazoline auxiliary provided an impressive stereoselectivity (70 de%) in the 8?? ring closure. Confirmation of the major isomer from the diastereomeric bicyclooctadienes was determined based on X-ray structure analysis of a SNF analog bearing (S)-phenylglycinol moiety. This first example of chiral induction generated by the trans-4,5-diphenyl oxazoline auxiliary in 8?? electrocyclization directly affords enantiomeric carboxylic acids (R = CO2H) which are key intermediates for elaboration to stereochemically homogeneous analogs of the SNF multidrug-resistance reversal agents. On the other hand, asymmetric Shi epoxidation and aspartate-catalyzed asymmetric epoxidation were adopted to convert racemic SNF analogs to their enantiomerically pure forms. While synthesizing the highly substituted cyclobutane core of bielschowskysin, tetraene substrates with 1,2-fused ring were cyclized to leading exclusively to endo products in the 8??, 6?? electrocyclization. In addition, the double ring closure was critically influenced by the methyl group adjacent to the aryl group. Progress toward the total synthesis of (+/-)-kingianin A, which is interested in its unique pentacyclic framework and potential biological activity, has been focused on model-based testing for 8??, 6?? electrocyclization and cation radical catalyzed Diels-Alder reaction. This issue is currently under active investigation in our laboratory.
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278 pg.
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The Graduate School, Stony Brook University: Stony Brook, NY.
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