Synthesis and NMR Spectroscopic Elucidation of Four Diastereoisomers of Oxygenated Bisabolane Side Chain

Abstract

Four possible stereoisomers of a model compound of highly O‐bearing bisabolane sesquiterpenes were synthesized and their NMR spectra were compared. Starting from isopulegol, allylic oxidation and Grignard reaction afforded a mixture of alcohols at C(8), which was separated. After metathesis reaction, both α‐ and β‐epoxides were obtained via non‐stereoselective epoxidation, while VO(OiPr)3‐catalyzed epoxidation afforded a single diastereoisomer selectively. NMR Spectra of twelve synthesized compounds, four stereoisomers of acetates, isobutyrates, and tiglates, were measured. A difference between C(8α)‐ and C(8β)‐acyloxy isomers was observed in the δ‐values of HC(8) in CDCl3. Within the 8β‐acyloxy compounds, the α‐ and the β‐epoxides were distinguished by either the J‐value of HC(8) or the chemical shift of CH2(9). Within the 8α‐acyloxy compounds, two epoxide isomers were distinguished by the J‐value of HC(10) in C6D6 or in CD3OD.

Enantiomeric Isopulegol as the Chiral Pool in the Total Synthesis of Bioactive Agents

“…Based on this background, Hirai and his research group decided to synthesise model compounds in 2015 starting from (À )-isopulegol 2. [145] TBS-protected (À )-2 was oxidised with SeO 2 to afford aldehyde 260, which was alkylated with allylmagnesium chloride giving a 1 : 1 mixture of 261 and 262. The configuration of the newly generated chiral centre was determined by advanced Mosher's method.…”

“…The configuration at C-8 was determined to be (S)-for 261 and (R)-for 262 from the difference in chemical shifts in the 1 H-NMR spectra (Scheme 49). [145] On the other hand, compounds 261 and 262 was subjected to to metathesis reaction and subsequent epoxidation with m-CPBA to provide epoxides (d.r. = 1:1), which was converted to esters 267-270 via deprotection followed by esterfication (Scheme 49).…”

“…= 1:1), which was converted to esters 267-270 via deprotection followed by esterfication (Scheme 49). [145] When NMR spectra of 267-270 recorded in CDCl 3 were compared, a distinct difference in chemical shifts was observed between 8α-and 8β-acyloxy isomers. Within the 8β-acyloxy compounds, α-epoxides 267 a-c and β-epoxides 268 a-c could be distinguished by the J-value of H-C( 8) and(or) the chemical shift of CH 2 (9).…”

Chemical Studies of Cremanthodium (Asteraceae) Species; Sesquiterpenoids and Related Compounds

“…42 Kuroda et al recently established the absolute configurations at C-8 and C-10 in a side chain of some bisabolane compounds by total synthesis. 43,44…”

Bisabolane, Oplopane, and Lignan Constituents of Cremanthodium campanulatum Collected in China

“…30 Kuroda et al recently established the absolute configurations at C-8 and C-10 in a side chain of some bisabolane compounds by total synthesis. 31,32 However, the absolute configuration at the C-8 position and the epoxide at C-10/C-11 in compounds 1 to 8 could not be determined using the spectroscopic methods because the requisite NMR data were not feasible to obtain as part of this study.…”