Abstract:[reaction: see text] Initial efforts toward the total synthesis of the antifungal antibiotics spirofungins A and B are reported. A short and efficient synthesis of the C9-C20 6,6-spiroketal fragments of both compounds is described. This asymmetric approach uses a very efficient alkylation of a lithiated N,N-dimethylhydrazone followed by spiroketal formation under acidic conditions.
“…In addition,equatorial methyl groups at the 2-or 8-position appear at lower field in the 13 C spectrum than axial methyl groups. [32] In all mixtures the configuration with bisaxial arrangement of the spiro C À O bonds was favoured ( Table 1). The minor isomer is expected to adopt configuration B or C stabilised by only one anomeric effect (Scheme 7).…”
An efficient and reliable multi-step synthesis of 251 natural product-like [5.5]-spiroketals on solid supports has been developed. As central key step, a double intramolecular hetero-Michael (DIHMA) reaction to alkynones was applied. The sequence allows for introduction of numerous substituents on the scaffold and for variation of stereochemistry. [5.5]-Spiroketals bearing an additional ketone were obtained in high overall yields. Further diversification was achieved by reduction of the ketone and reductive amination using polymer-supported borohydride, Grignard reaction and conversion to oxime derivatives in the solution phase.
“…In addition,equatorial methyl groups at the 2-or 8-position appear at lower field in the 13 C spectrum than axial methyl groups. [32] In all mixtures the configuration with bisaxial arrangement of the spiro C À O bonds was favoured ( Table 1). The minor isomer is expected to adopt configuration B or C stabilised by only one anomeric effect (Scheme 7).…”
An efficient and reliable multi-step synthesis of 251 natural product-like [5.5]-spiroketals on solid supports has been developed. As central key step, a double intramolecular hetero-Michael (DIHMA) reaction to alkynones was applied. The sequence allows for introduction of numerous substituents on the scaffold and for variation of stereochemistry. [5.5]-Spiroketals bearing an additional ketone were obtained in high overall yields. Further diversification was achieved by reduction of the ketone and reductive amination using polymer-supported borohydride, Grignard reaction and conversion to oxime derivatives in the solution phase.
“…104 A very efficient alkylation of a lithiated N,N-dimethylhydrazone of a chiral ketone (33, R 2 ) Me, R 1 ) CH 2 CH(Me)-CH(O(TBS))CH 2 O(PMB)) followed by spiroketal formation under acidic conditions was also used in a short synthesis of the 6,6-spiroketal fragments 38 and 39 useful for synthesis of the antifungal antibiotics spirofungins A and B. 105 Another alkylation reaction of the lithiated N,N-dimethylhydrazones of elaborate methyl ketones 33 (R 1 ) H, R 2 ) chiral O-protected substituted trihydroxynonyl) with suitable, protected iodide 40 afforded linear spiroketal intermediates. After functional group adjustment, these advanced intermediates were cyclized to their respective spiroketals 41 (R ) H, R ) Me), which constituted subunits in the asymmetric synthesis of the macrolide antibiotics (+)-rutamycin B and (+)-oligomycin.…”
Section: Alkylation Of Nn-dimethylhydrazonesmentioning
“…It was also observed that each isolated pure spiroketal led to the same 30:70 equilibrium mixture under very mild acidic conditions (CDCl 3 ). 23 Synthesis of the Spiroketal Segment of Spirofungins A and B by Dias et al …”
Section: 2 Polyketide Antibiotics With a Nonanomeric
[66]-spiroketal ...mentioning
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