Methods for Determination of Absolute Configurations of Chiral Diols by THENA Ester and NMR Shift Difference

Abstract

Determination of the absolute configuration of chiral secondary diols by chiral derivatizing agent (CDA) and NMR shift difference is of great challenge due to the complication from the interference of the aromatic anisotropic shielding effect of the two CDAs in close proximity. In this work, tetrahydro-1,4-epoxynaphthalene-1-carboxylic acid (THENA) was introduced as an alternative CDA for diols to overcome such complexity. Since the deshielding effect of THENA is weaker than the shielding effect of other CDAs, THENA would allow the direct analysis of the chemical shift difference in determining the absolute configuration of the chiral diols. In addition, an analytical method based on Riguera’s model could also be used to confirm the assignment. With a good agreement between the assigned configuration based on both analytical models, the absolute configuration of the chiral diols could be assigned with reliability.

Key words

absolute configuration - chiral derivatizing agent - diols - NMR shift difference - natural products - stereochemistry - THENA

Publication History

Received: 01 February 2022

Accepted after revision: 09 March 2022

Article published online:
06 May 2022

• References and Notes

• 1 New address: K. Dolsophon, Department of Chemistry and Center of Excellence for Innovation in Chemistry, Faculty of Science, Srinakharinwirot University, Bangkok 10110, Thailand.
• 2 New address: J. Soponpong, Chulalongkorn University Drug Discovery and Drug Development Research Center, Chulalongkorn University, Bangkok, Thailand.
• 3a Allenmark S, Gawronski J. Chirality 2008; 20: 606
• 3b Kong LY, Wang P. Chin. J. Nat. Med. 2013; 11: 193
• 3c Structure Elucidation in Organic Chemistry: The Search for the Right Tools; Cid M.-M, Bravo J. Weinheim: Wiley-VCH; 2015
• 4a Seco JM, Quiñoá E, Riguera R. Chem. Rev. 2004; 104: 17
• 4b Trost BM, Belletire JL, Godleski S, McDougal PG, Balkovec JM. J. Org. Chem. 1986; 51: 2370
• 4c Seco JM, Quiñoá E, Riguera R. Tetrahedron: Asymmetry 2001; 12: 2915
• 4d Porto S, Quiñoá E, Riguera R. Tetrahedron 2014; 70: 3276
• 4e Latypov SK, Seco JM, Quiñoá E, Riguera R. J. Org. Chem. 1996; 61: 8569
• 5a Seco JM, Quiñoá E, Riguera R. Chem. Rev. 2012; 112: 4603
• 5b Freire F, Seco JM, Quiñoá E, Riguera R. Org. Lett. 2010; 12: 208
• 5c Seco JM, Martino M, Quiñoá E, Riguera R. Org. Lett. 2000; 2: 3261
• 5d Freire F, Seco JM, Quiñoá E, Riguera R. J. Org. Chem. 2005; 70: 3778
• 6 Sungsuwan S, Ruangsupapichart N, Prabpai S, Kongsaeree P, Thongpanchang T. Tetrahedron Lett. 2010; 51: 4965
• 7 Arita S, Yabuuchi T, Kusumi T. Chirality 2003; 15: 609
• 8a Isaka M, Chinthanom P, Sappan M, Supothina S, Boonpratuang T. Mycenadiols (compound B) were provided by Dr. Masahiko Isaka, see. 2014: 97 ; 909 (+)-Goniodiol (compound E) was provided by Prof. Dr. Patoomratana Tuchinda, see:
• 8b Thienthiti K, Tuchinda P, Wongnoppavich A, Anantachoke N, Soonthornchareonnon N. Pharm. Sci. Asia 2017; 44: 86
• 9 The Δδ_H value of compounds B and E were sufficient for determining the absolute configuration of only one chiral center.
• 10 Kornsakulkarn J, Palasarn S, Choowong W, Thongpanchang T, Boonyuen N, Choeyklin R, Boonpratuang T, Isaka M, Thongpanchang C. J. Nat. Prod. 2020; 83: 905
• 11 CCDC 2144692 contains the supplementary crystallographic data for this paper (excluding structure factors). The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/structures.
• 12 Due to the sign distribution error, the absolute configuration of compounds B-i and B-ii might not be properly assigned by this model due to the small number of data points.