Quebrachamine group, synthesis

In view of the importance of vindoline (44) as a constituent of the oncolytic bisindole alkaloid vinblastine, methods for the synthesis of both vindorosine (43) and vindoline from members of the quebrachamine and vincadifformine groups have been extensively investigated. The first results... 

Yet another synthesis of the aldehydo-acid 430 by Takano s group (277) constitutes a further formal synthesis of ( )-quebrachamine. Here, butyro-nitrile was bisalkylated by allyl bromide, and the product converted into the iodolactone 441 by reaction with iodine in mild aqueous alkali. Hydrolysis then gave the corresponding alcohol, which on further hydrolysis and... 

Fig. 37), the late-stage enantioselective alkene RCM required the closure reaction onto one of two sterically hindered vinyl groups at a congested quaternary carbon in the presence of a potentially problematic tertiary amine moiety. Through an extensive screen of chiral catalysts, gratifyingly, the desired tetracycle (142) was obtained in 84% yield and 96% ee, which allowed the completion of total synthesis of (+)-quebrachamine (139). 

An enantioselective synthesis of Aspidosperma alkaloid quebrachamine, summarized in Scheme 12.4, has been recently accomplished [7]. The late-stage RCM requires ring-dosure onto one of two stericaUy hindered vinyl groups at a congested aU-carbon quaternary center [8] in the presence of a Lewis basic tertiary amine. [Mo]-diolate complexes (e.g., [Mo]-II, Scheme 12.1) do not promote any reaction even under fordng conditions (up to 50 mol% catalyst, up to 80 °C). When... 

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