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Title: New route to the API ropinirole hydrochloride and towards new synthetic applications of squaramides
Author: Yousuf, Zeshan
ISNI:       0000 0004 5346 9558
Awarding Body: University of Southampton
Current Institution: University of Southampton
Date of Award: 2015
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This thesis describes our efforts in developing a new synthesis of the active pharmaceutical ingredient (API) ropinirole hydrochloride, used in the symptomatic treatment of Parkinson’s disease and Restless Leg Syndrome. The API in Requip™ (marketed by GlaxoSmithKline) is currently prepared in 12% overall yield using a nine-step sequence, however, several generic routes have since been established in the pharmaceutical market. Herein we describe a shorter and more efficient route to ropinirole hydrochloride that could prove attractive from an industrial perspective. The strategies employed in developing the new synthesis of the API are presented - adopting Plieninger’s approach to 4-substituted indoles with a contemporary twist. Key transformations include the use of a dissolving metal reduction followed by an ozonolysis under flow to construct the API’s heterocyclic core. In our first approach the target is attained in six-steps from 1-aminonaphthalene. However, by increasing the oxidation level of the starting material we were able to achieve a synthesis of ropinirole hydrochloride in four steps from a commercial starting material. Also described in this thesis are our efforts towards probing the synthetic versatility of squaramides. Preliminary results indicate that the stabilisation exhibited by their derivatives may lead to alternative thermal rearrangement pathways, complimentary to squarates.
Supervisor: Harrowven, David Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: QD Chemistry