Taxotere is the trade name for the synthetic anticancer drug docetaxel, whose structure

Chapter 22, Problem 22.81

(choose chapter or problem)

Taxotere is the trade name for the synthetic anticancer drug docetaxel, whose structure closely resembles the naturally occurring compound taxol, which is isolated from the Pacifi c yew tree (Section 5.5). N O O O docetaxel O OH O O O O O H O OH HO H OH C NHR H3O+ O (CH3)3CO carbamate C CH2 CO2 RNH3 + CH3 CH3 + + a. Taxols limited water solubility led to an extensive search for related compounds with increased water solubility. What structural features give docetaxel a better water solubility profi le? b. Docetaxel contains a carbamate (labeled in red), a functional group with a carbonyl group bonded to a nitrogen and oxygen atom. Draw three more resonance structures for a carbamate (in addition to the Lewis structure with all neutral atoms given). Rank all four resonance structures in order of increasing stability. c. A carbamate with a tert-butoxy group [(CH3)3CO ] is hydrolyzed according to the given equation. Draw a stepwise mechanism for the hydrolysis of a carbamate to the three products shown. d. Assuming that all ester and carbamate bonds are cleaved, draw all products formed when docetaxel is hydrolyzed with aqueous acid.