Yoshimura Aya, Kishimoto Shinji, Nishimura Shinichi, Otsuka Saori, Sakai Yuki, Hattori Akira, Kakeya Hideaki
Department of System Chemotherapy and Molecular Sciences, Division of Bioinformatics and Chemical Genomics, Graduate School of Pharmaceutical Sciences, Kyoto University , Kyoto 606-8501, Japan.
J Org Chem. 2014 Aug 1;79(15):6858-67. doi: 10.1021/jo500906v. Epub 2014 Jul 11.
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.
最近有人提出了一种基于¹H NMR数据预测烷基链中1,3 - 二甲基取代相对立体化学的简单方法；位于甲基取代次甲基碳之间的亚甲基质子的Δδ值可用于预测。在此，我们将这种经验性的“偕质子规则”应用于来自链霉菌属的脂肽verucopeptin。为了确定verucopeptin中1,3,5 - 三甲基取代烷基链的绝对立体化学，我们通过氧化裂解将相应的烷基链转化为羧酸。偕质子规则明确预测相对立体化学为31S*,33S*,35R*。通过合成四种可能的非对映异构体并比较它们的NMR光谱，这一预测得到了明确证实。此外，我们使用已报道的化合物和我们合成的化合物重新研究了偕质子规则。我们的结果有力地表明，该规则是可靠的，至少对于预测2,4 - 二甲基化和2,4,6 - 三甲基化脂肪酸的立体化学是如此。
