Study on the Absolute Configurations of 3‐Alkylphthalides using TDDFT Calculations of Chiroptical Properties

Abstract

Absolute configurations (ACs) of 3-alkylphthalides including natural products (-)-3-n-butylphthalide ((-)-1) and fuscinarin have been studied using chiroptical properties and quantum chemical calculation. Electronic circular dichroism and optical rotatory dispersion spectra of (S)-1 predicted adopting time-dependent density functional theory and hybrid functionals coincide very well with the experimental and literature data of (-)-1, leading unambiguously to AC assignment as S for levorotatory isomer. The relationship between structures and chiroptical properties of 3-alkylphthalides were also studied using theoretical calculation. It is found that when the alkyl group is adjacent to the single chiral center in the molecule, both the length of the alkyl side chain and the polarity of solvent may exert significant effect on electronic circular dichroism spectra. On the basis of these observations, it is recommended that the long-chain alkyl group may be replaced by at least propyl instead of methyl group in such compounds. The present work shows that combination of chiroptical properties and ab initio calculations can provide a feasible and reliable way to the AC establishment of novel 3-alkylphthalide derivatives with a high degree of confidence.

Enantioseparation, Stereochemical Assignment and Chiral Recognition Mechanism of Sulfoxide-Containing Drugs

“…However, it might be interesting and useful to establish directly their stereochemistry without reference samples and spectra. Presently, ECD spectra together with quantum chemical calculations using time-dependent density functional theory (TDDFT) have provided a feasible and reliable way to facilitate the AC assignments of chiral drugs and natural products [ 15 , 18 , 40 , 41 , 42 , 43 , 44 ]. Hence, TDDFT calculations will be adopted to simulate ECD spectra of sulfoxides in this study.…”

Total synthesis of xiamenmycin C and all of its stereoisomers: stereochemical revision

“…Reaction (±) 8 with (S)-O-methyl mandelic acid provided a pair of diastereomeric esters 16 ( 17 (R f = 0.5, 1:1 DCM/EtOAc). After chromatography separation, each diastereomer was hydrolyzed using sodium methoxide [8] 13 C NMR spectra and NOE experiments, and comparison of the experimental CD spectra with the calculated spectra using TDDFT method [18,19] ( Figure 2). The data of (2R,3S)-23 were in agreement with those reported [1] for the natural product.…”

Two New Diterpenoids from Cell Cultures of <i>Salvia miltiorrhiza</i>

“…The absolute configuration of 1 was established by circular dichroism (CD) spectrum. In a previous paper, 15) it was reported that the S configuration of chiral center (C-13) in five-membered α,β-unsaturated lactone ring exhibits positive Note * To whom correspondence should be addressed. e-mail: jgdai@imm.ac.cn The authors declare no conflict of interest.…”