Total Synthesis and Stereochemical Assignment of cis-Uvariamicin I and cis-Reticulatacin

Abstract

Diastereoisomeric mixtures of cis-uvariamicin I (15R,16R,19S,20S,36S and 15S,16S,19R,20R,36S) andcis-reticulatacin (17R,18R,21S,22S,36S and 17S,18S,21R,22R,36S) weresynthesizedtodetermine the stereochemistry of the natural products isolated from Annona muricata. Itwasnotpossibleto resolve a mixture of the four synthetic isomers using chiral HPLC, but the mixed isomers could be distinguished using chiral HPLC EIMSwithextractedfragmentionanalysis. Comparisonofsynthetic standards with the natural isolate revealed that cis-uvariamicin I and cis-reticulatacin are present in nature as mixtures of threo-cis-threo diastereoisomers. It is suggested that the nomenclature for the natural products is amended as follows: (15R,16R,19S,20S,36S)-cis-uvariamicin I (cis-uvariamicin IA); (15S,16S,19R,20R,36S)-cis-uvariamicin I (cis-uvariamicin IB); (17R,18R,21S,22S,36S)-cis-reti culatacin (cis-reticulatacin A); (17S,18S,21R,22R,36S)-cis-reticulatacin (cis-reticulatacin B)