Conformational Analysis of (+)-Germacrene D-4-ol Using the Crystalline Sponge Method to Elucidate the Origin of its Instability

Youngcheol Jung; Takaaki Mitsuhashi; Ko Kageyama; Takashi Kikuchi; Sota Sato; Makoto Fujita

doi:10.1002/chem.202400512

Conformational Analysis of (+)-Germacrene D-4-ol Using the Crystalline Sponge Method to Elucidate the Origin of its Instability

Chemistry. 2024 May 14:e202400512. doi: 10.1002/chem.202400512. Online ahead of print.

Authors

Youngcheol Jung¹, Takaaki Mitsuhashi², Ko Kageyama¹, Takashi Kikuchi³, Sota Sato¹, Makoto Fujita⁴

Affiliations

¹ The University of Tokyo, Department of Applied Chemistry, School of Engineering, JAPAN.
² Institute for Molecular Science, Division of Advanced Molecular Science, JAPAN.
³ Rigaku Corporation, n/a, JAPAN.
⁴ The University of Tokyo Graduate School of Engineering Faculty of Engineering: Tokyo Daigaku Daigakuin Kogakukei Kenkyuka Kogakubu, Applied Chemistry, Mitsui Link Lab Kashiwanoha 1, FS CREATION, 6-6-2 Kashiwanoha, Kashiwa, Chiba, 277-0882, Chiba, JAPAN.

PMID: 38742865
DOI: 10.1002/chem.202400512

Abstract

Unsaturated cyclic terpenes often exhibit instability due to the proximation of C=C bonds in the cyclic skeleton, leading to nonenzymatic degradation. In this study, the crystalline sponge (CS) method was employed for the X-ray conformational analysis of a minute amount of oily and cyclic terpene compound, (+)-germacrene D-4-ol, which was produced by a terpene synthase OILTS under in vitro conditions. The CS method revealed a reactive conformation of the cyclic terpene with proximal double bonds. Under weakly acidic in vivo conditions, OILTS gave four pseudo-natural products or artifacts. The CS method also elucidated the structures of these degraded compounds, proposing a degradation mechanism triggered by the transannular reactions.

Keywords: Natural Product; conformational analysis; crystalline sponge method; non-enzymatic reaction; terpenoids.