title: Prediction and determination of the stereochemistry of the 1,3,5-trimethyl-substituted alkyl chain in verucopeptin, a microbial metabolite.
abstract: For the prediction of the relative stereochemistry of 1,3-dimethyl substitution in alkyl chains, a simple approach based on (1)H NMR data was recently proposed; Δδ values of methylene protons located between methyl-substituted methine carbons can be diagnostic for predicting it. Here we applied this empirical "geminal proton rule" to verucopeptin, a lipopeptide from Streptomyces sp. To determine the absolute stereochemistry of the 1,3,5-trimethyl-substituted alkyl chain in verucopeptin, we converted the corresponding alkyl chain to a carboxylic acid by oxidative cleavage. The geminal proton rule clearly predicted the relative stereochemistry as 31S*,33S*,35R*. This prediction was definitely confirmed by synthesizing four possible diastereomers and comparing their NMR spectra. Furthermore, we reinvestigated the geminal proton rule using reported compounds and our synthesized compounds. Our result strongly suggests that the rule was solid, at least for predicting the stereochemistry of 2,4-dimethylated and 2,4,6-trimethylated fatty acids.
authors.affiliation: Department of System Chemotherapy and Molecular Sciences, Division of Bioinformatics and Chemical Genomics, Graduate School of Pharmaceutical Sciences, Kyoto University , Kyoto 606-8501, Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Yoshimura
authors.forename: Shinji
authors.initials: S
authors.lastname: Kishimoto
authors.forename: Shinichi
authors.initials: S
authors.lastname: Nishimura
authors.forename: Saori
authors.initials: S
authors.lastname: Otsuka
authors.forename: Yuki
authors.initials: Y
authors.lastname: Sakai
authors.forename: Akira
authors.initials: A
authors.lastname: Hattori
authors.forename: Hideaki
authors.initials: H
authors.lastname: Kakeya
mesh_terms: D002264:Carboxylic Acids / Q000737:chemistry*; D047630:Depsipeptides / Q000138:chemical synthesis* / Q000737:chemistry* / Q000378:metabolism; D005227:Fatty Acids / Q000138:chemical synthesis* / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D013237:Stereoisomerism
chemical_list: D002264:Carboxylic Acids; D047630:Depsipeptides; D005227:Fatty Acids; C082424:verucopeptin