Crystalline‐Sponge‐Based Structural Analysis of Crude Natural Product Extracts

Abstract

Characterization of complex natural product mixtures to the absolute structural level of their components often requires significant amounts of starting materials and lengthy purification process,followed by arduous structure elucidation efforts.The crystalline sponge (CS) method has demonstrated utility in the absolute structure elucidation of isolated organic compounds at miniscule quantities compared to conventional methods.Inthis work, we developed anew CS-based workflow that greatly expedites the in-depth structural analysis of crude natural product extracts.U sing ac rude extract of the red alga Laurencia pacifica, we showed that CS affinity screening prior to compound isolation enables prioritization of analytes present in the extract, and we subsequently resolved the molecular structures of six sesquiterpenes with stereochemical clarity from around 10 mg crude extract. This study demonstrates anew chemotyping workflow that can greatly accelerate natural product discovery from complex samples.A typical workflow for natural product isolation followed by structure elucidation often begins with collecting and processing large quantity of bulk materials from living organisms, such as plants,a nimals,f ungi, algae,a nd sponges.

Structure determination of terpenes by the crystalline sponge method

“…These interactions include π-π, CH-π, and charge-transfer interactions. The technique was first introduced by Fujita et al [1] in 2013 and since then has grown rapidly and proven helpful in the structure elucidation of natural products [2], [3] volatile compounds [4], [5], ozonides [6], metabolites [7], in studying reaction mechanisms [8], [9] and in absolute structure determination [10], [11]. With the success of the crystalline sponge method many researchers developed alternative crystalline sponges [12], [13].…”

“…Absolute structure determination of other terpenes such as astellifadiene [19], LphTPS-A -a sesquiterpene synthase [20] -and prenyltransferase-terpene synthase [3] has been previously achieved using the crystalline sponge method, demonstrating that this technique is suitable for structure determination of complex natural products.…”

Natural Products as a Foundation for Drug Discovery

“…To date, most of the applications of this method to characterizing natural‐product structures were performed by the Fujita laboratory (Brkljaca et al., ; Kai, Sogame, Sakurai, Nasu, & Fujita, ; Lee, Hoshino, Fujita, & Urban, ; Matsuda et al., ; Urban, Brkljaca, Hoshino, Lee, & Fujita, ; Yoshioka, Inokuma, Hoshino, Sato, & Fujita, ), although another group has published the absolute configuration determination of a plant metabolite, asarinin, using crystalline‐sponge methods (Li, Yang, Gu, & Di, ). It has been reported that crystalline sponges could be used as an affinity matrix to trap sesquiterpenes from a crude red algal extract for analysis (Wada et al., ).…”

CANPA: Computer-Assisted Natural Products Anticipation

“…Extending knowledge and principles of structural chemical diversity is one fundamental outcome derived from the natural product (NP) discovery process. From an applied standpoint, this process often consists of an extraction step followed by a spate of finely tuned scenarios, each making use of different targeting strategies (i.e., bioactivity-based (1)(2)(3)(4) and/or structure-based (5)(6)(7)(8)(9)), leading to the identification of NP structures. Remarkably, discovery-based workflows systematically need a crucial NPs database search that identifies and filters out any known compounds that are present in the extract.…”