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

• Published in: Journal of organic chemistry Vol. 74; no. 18; pp. 6924 - 6928
• Main Authors: Abdel Ghani, Sherif B, Chapman, James M, Figadère, Bruno, Herniman, Julie M, Langley, G. John, Niemann, Scott, Brown, Richard C. D
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 18.09.2009; Amer Chemical Soc
• Subjects: Analytical chemistry; Annona - chemistry; Antineoplastic Agents, Phytogenic - chemical synthesis; Biological Products - chemistry; Biological Products - isolation & purification; Chemistry; Chemistry, Organic; Chromatographic methods and physical methods associated with chromatography; Chromatography, High Pressure Liquid; Exact sciences and technology; Furans - chemical synthesis; Furans - chemistry; Heterocyclic compounds; Heterocyclic compounds with o, s, se, te hetero atom and condensed derivatives; Lactones - chemical synthesis; Lactones - chemistry; Molecular Structure; Organic chemistry; Other chromatographic methods; Physical Sciences; Preparations and properties; Science & Technology; Stereoisomerism; SOLAMIN; H-1-NMR; SEEDS; ABSOLUTE-CONFIGURATION; SQUAMOSA; RECENT PROGRESS; ROLLINIASTATIN-1; MECHANISMS; ANNONACEOUS ACETOGENINS; Furan derivatives; HPLC chromatography; Chiral compound; Natural compound; Stereochemistry; Oxygen heterocycle; Total synthesis; Polyketide; Dicotyledones; Angiospermae; Threo stereoisomer; Spermatophyta; Annonaceae; Acetogenin; Chemical synthesis; Diastereomer
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo9012578

Diastereoisomeric mixtures of cis-uvariamicin I (15R,16R,19S,20S,36S and 15S,16S,19R,20R,36S) and cis-reticulatacin (17R,18R,21S,22S,36S and 17S,18S,21R,22R,36S) were synthesized to determine the stereochemistry of the natural products isolated from Annona muricata. It was not possible to resolve a mixture of the four synthetic isomers using chiral HPLC, but the mixed isomers could be distinguished using chiral HPLC EIMS with extracted fragment ion analysis. Comparison of synthetic 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-reticulatacin (cis-reticulatacin A); (17S,18S,21R,22R,36S)-cis-reticulatacin (cis-reticulatacin B).