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Synthetic studies towards sieboldine a and a macrocyclic precursor of bielschowskysin

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7DEOH&RQGLWLRQVIRUYLQ\OLRGLGHIRUPDWLRQ
7DEOH5HDFWLRQRSWLPLVDWLRQIRU6RQRJDVKLUDUHDFWLRQ
7DEOH&RQGLWLRQVIRUFRQYHUVLRQRIK\GUR[\OWRKDOLGH
7DEOH,QWUDPROHFXODUNHWRHVWHUDON\DWLRQ
7DEOH$WWHPSWVWRPDNHĮSKRVSKLQHSKRVSKLWHODFWRQH
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)LJXUH1DWXUDO3URGXFWVDV'UXJV
)LJXUH&KDUDFWHULVWLFVRI$O]KHLPHU¶V'LVHDVH
)LJXUH  6FKHPDWLF GLDJUDP RI KRZ DFHW\OFKROLQH LV XVHG LQ

QHXWURWUDQVPLVVLRQ

)LJXUH5HSUHVHQWDWLYH/\FRSRGLXP$ONDORLGV
)LJXUH5HODWLYH5DWHRI)RUPDWLRQRI/DFWRQHV
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)LJXUH5DWLRQDOHIRU'LDVWHUHRVHOHFWLYH&RQMXJDWH$GGLWLRQ
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)LJXUH  6WUXFWXUH RI %LHOVFKRZVN\VLQ  DQG  
FRUDO

)LJXUH6WHUHRVHOHFWLYH$GGLWLRQWRNHWRQH
)LJXUH12(([SHULPHQWIRU
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)LJXUH6LQJOHFU\VWDO;UD\VWUXFWXUHRI
)LJXUH12(([SHULPHQWIRU
)LJXUH  )RUPDWLRQ RI DF\ONHWHQH DQG WUDSSLQJ WR DOORZ WUDQVHVWHULIFDWLRQ


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6FKHPH0RGHOVWXG\E\3URI6WROW]¶VJURXSXVLQJULQJH[SDQVLRQDVWKH
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6FKHPH3URSRVHGPHFKDQLVPIRUIRUPDWLRQRIELF\FOLF
6FKHPH0DFURF\FOLVDWLRQDWWHPSWE\0U.DUWKLUN6HNDU
6FKHPH3DTXHWWH¶VV\QWKHVLVRI$FHURVROLGH
6FKHPH3DWWHQGHQ¶VV\QWKHVLVRIELVGHR[\ORSKRWR[LQ
6FKHPH3DWWHQGHQ¶VDOWHUQDWHDSSURDFKWRIXUDQRFHPEUDQRLGV
6FKHPH  7RNRUR\DPD¶V .QRHYHQDJHO FRQGHQVDWLRQ PDFURF\FOLVDWLRQ

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6FKHPH0DUVKDOO¶VDSSURDFKHVWRIXUDQRFHPEUDQRLGV
6FKHPH'RQKRH¶VV\QWKHVLVRIGHR[\SXNDOLGH
6FKHPH7UDXQHU¶VV\QWKHVLVRI%LSLQQDWLQ-
6FKHPH0LOGR[LGDWLRQRIIXUDQZLWK0033
6FKHPH)RUPDWLRQRIF\FOLFHQGRSHUR[LGHDQGUHDUUDQJHPHQW
6FKHPH%DUELHUDQG$OGROPDFURF\FOLVDWLRQV
6FKHPH,QLWLDOUHWURV\QWKHVLVRI%LHOVFKRZVN\VLQ
6FKHPH3URWRFROVWRSUHSDUHFKLUDODOOHQHVDQGSURSDUJ\OLFDOFRKROV
6FKHPH3UHSDUDWLRQRIWHUWLDU\DOFRKRO
6FKHPH)RUPDWLRQRIWKHSURSDU\OLFDOFRKRO
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6FKHPH3RVVLEOHPHFKDQLVPVWRH[SODLQWKHORVVLQVWHUHRFKHPLVWU\
6FKHPH8QVXFFHVVIXODWWHPSWVWRFRQVWUXFWDSURSDUJ\OLFDOFRKRO
6FKHPH6HFRQGJHQHUDWLRQUHWURV\QWKHVLV
6FKHPH6\QWKHVLVRIODFWRQHIRUFRXSOLQJ
6FKHPH0HWKRGVWRV\QWKHVLVHYLQ\OLRGLGHV
6FKHPH6\QWKHVLVRI$OGHK\GH
6FKHPH6\QWKHVLVRI=YLQ\OLRGLGHV
6FKHPH7HVWLQJWKHHQGJDPHYLDELOLW\
6FKHPH&RXSOLQJDQGIDLOHGSURSDUJ\ODWLRQUHDFWLRQ
6FKHPH&RPPRQO\3URSRVHG0HFKDQLVPIRU6RQRJDVKLUD5HDFWLRQ
6FKHPH  6RQRJDVKLUD &RXSOLQJ DQG 3UHSDUDWLRQ RI %DUELHU
PDFURF\FOLVDWLRQSUHFXUVRU


6FKHPH3UHSDUDWLRQRISURSDUJ\OLFEURPLGH
6FKHPH5HWURV\QWKHVLVYLDDNHWRHVWHULQWHUPHGLDWH
6FKHPH3UHSDUWLRQRIKRPRSURSDUJ\OLFDOFRKRO
6FKHPH3UHSDUWLRQRIDON\QHVXEVWUDWHVIRUFRXSOLQJ
6FKHPH  $WWHPSWHG 6RQRJDVKLUD DQG 0DFURF\FOLVDWLRQ YLD .HWRHVWHU
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