Synthetic approaches to the vineomycinones
Abstract (Summary)Restricted Item. Print thesis available in the University of Auckland Library or available through Inter-Library Loan. The furanoketone (24) and the dimethoxy ketone (103), envisaged as key intermediates for syntheses of the vineomycins and fridamycins, respectively were prepared from anthrarufin (18) utilizing reductive mono-Claisen rearrangements. The furanoketone (24) was obtained in 69% overall yield and the dimethoxy ketone (103) in 84% overall yield. The ketones (24) and (103) were reacted with a titanium reagent (75), prepared from the lithium enolate of (I)-menthyl acetate to give the butanoates (74) and (102), respectively. The diastereomeric pairs were separated by HPLC. No diastereoselection was observed in these reactions. The absolute configurations of the methoxy substituted compounds (102a,b) were established when one of the diastereomers (102b) was converted to the natural product (65), which also achieved a total synthesis of fridamycin E. The absolute configurations of the furanosubstituted compounds (74a, b) were established by comparison of their 1H NMR behaviour in the presence of Eu(hfc)3 with the corresponding fridamycin derivatives (102a,b) under the same conditions. The absolute configurations were confirmed by comparison of the 1H NMR behaviour of the methyl esters (73a,b) and (76a,b) in the presence of the chiral solvating agent, 2,2,2-trifluoro-1-(9-anthryl)ethanol (111). Attempts to obtain optical rotatory dispersion curves, and to separate mixtures of the enantiomeric methylbutanoates (73a,b) by chromatography on a chiral stationary phase were both unsuccessful. The furanobutanoate (73) was converted to the acetal (116) in preparation for the construction of the C-glycoside of the vineomycins. The reactivity of the reagent (75) and its potential for achieving asymmetric induction was assessed by its reaction with benzaldehyde, and the effect of an ortho-methoxy or hydroxyl group was investigated by reaction of (75) with the anthraquinone aldehydes (77) and (78). The reagent was found to be very reactive towards these aldehydes, although levels of asymmetric induction were low. Thus the propanoates (137), (150), and (151) were prepared and the diastereomeric pairs were separated by HPLC. The anthraquinonyl propanoates (150) and (151) are potential intermediates for syntheses of nor-vineomycins or fridamycins. The use of the chiral sulphoxide (79) as an acetate synthon for the construction of the butanoate side chain was investigated. The sulphinyl ester (166) was prepared, however problems were encountered with the desulphurization, probably due to interference by the quinone carbonyl groups. Attempts to add the sulphoxide (79) to the trimethoxyanthracene (171) were unsuccessful.
School Location:New Zealand
Source Type:Master's Thesis
Date of Publication:01/01/1992