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Title: Application of the [5+2] photocycloaddition to alkaloid synthesis and the total synthesis of (±)-neostenine
Author: Lainchbury, Michael D.
ISNI:       0000 0004 2677 6480
Awarding Body: University of Bristol
Current Institution: University of Bristol
Date of Award: 2008
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A study towards the total synthesis of cephalotaxine was attempted by testing the applicability of the maleimide [5+2] photocycloaddition to a substrate that was isoelectronic with maleimide. A model system was prepared using indole quinones. Although these compounds were shown to be photochemically active, no products were isolated. After the study was undertaken, new insight into the mechanism of the maleimide [5+2] photocycloaddition demonstrated that the existing hypothesis that a concerted [2+2] cycloaddition process was not valid. The mechanism was actually found to involve an a-cleavage of the amide bond in maleimides. This indicated that [5+2] photocycloaddition with indole quinones may not be achievable. Four different approaches were investigated towards the total synthesis of selaginoidine. The first two approaches would have led to advanced synthetic intermediates, had irradiation not demonstrated a preference for the [2+2] cycloaddition process. A third disconnection provided a [5+2] photocycloadduct in moderate yield. Unfortunately elaboration of the product was difficult, particularly with a-alkylation. With this in mind a fourth strategy was undertaken whereby aalkylation would be avoided. This route has proven to be successful and rapidly affords an intermediate that may well be successful for the synthesis of (±)-selaginoidine. The synthesis of (±)-neostenine has been achieved in 14 steps from furan in a 9.5% overall yield. Anti selective SN2' bislactone CZ-desymmetrisation provided the first key intermediate, which contained four of the seven requisite stereocentres of (±)-neostenine. Two more centres were established with complete control from a key [5+2] photocycloaddition. Methylation of the lactone completed the final of the seven stereocentres required for (±)-neostenine.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available