Manabu Hoshino

Astellifadiene: Structure Determination by NMR Spectroscopy and Crystalline Sponge Method, and Elucidation of its Biosynthesis

Genome mining of a terpene synthase gene from Emericella variecolor NBRC 32302 and its functional expression in Aspergillus oryzae led to the production of the new sesterterpene hydrocarbon, astellifadiene (1), having a 6-8-6-5-fused ring system. The structure of 1 was initially investigated by extensive NMR analyses, and was further confirmed by the crystalline sponge method, which established the absolute structure of 1 and demonstrated the usefulness of the method in the structure determination of complex hydrocarbon natural products. Furthermore, the biosynthesis of 1 was proposed on the basis of isotope-incorporation experiments performed both in vivo and in vitro. The cyclization of GFPP involves a protonation-initiated second cyclization sequence, 1,2-alkyl migration, and 1,5-hydride shift to generate the novel scaffold of 1.

Phosphine‐Catalyzed β,γ‐Umpolung Domino Reaction of Allenic Esters: Facile Synthesis of Tetrahydrobenzofuranones Bearing a Chiral Tetrasubstituted Stereogenic Carbon Center

An enantio-, diastereo-, regio-, and chemoselective phosphine-catalyzed β,γ-umpolung domino reaction of allenic esters with dienones has been developed for the first time. The designed sequence, involving oxy-Michael and Rauhut-Currier reactions, produced highly functionalized tetrahydrobenzofuranones, bearing a chiral tetrasubstituted stereogenic center, in up to 96 % ee.

The crystalline sponge method updated

The protocols of the crystalline sponge method, particularly those in the soaking, data collection and refinement processes, are considerably improved to give reliable structural information.

Where is the Oxygen? Structural Analysis of α‐Humulene Oxidation Products by the Crystalline Sponge Method

Crystal structures of α-humulene, a cyclic sesquiterpene, and its oxidized subproducts, were analyzed by the crystalline sponge method. Regio- and stereochemistry, including absolute configuration when a chiral oxidant was applied, and the stable conformations of all the scaffold-related compounds were successfully determined for samples on a 5-50 μg scale.

In Situ Observation of Thiol Michael Addition to a Reversible Covalent Drug in a Crystalline Sponge

A reversible Michael addition reaction between thiol nucleophiles and cyanoenones has been previously postulated to be the mechanism-of-action of a new family of reversible covalent drugs. However, the hypothetical Michael adducts in this mechanism have only been detected by spectroscopic methods in solution. Herein, the crystallographic observation of reversible Michael addition with a potent cyanoenone drug candidate by means of the crystalline-sponge method is reported. After inclusion of the cyanoenone substrate, the sponge crystal was treated with a thiol solution. Subsequent crystallographic analysis confirmed the single-crystal-to-single-crystal transformation of the substrate into the impermanent Michael adduct.

Undeniable Confirmation of the syn-Addition Mechanism for Metal-Free Diboration by Using the Crystalline Sponge Method

The stereochemical outcome of the recently developed metal-free 1,2-diboration of aliphatic alkenes has, until now, only been elucidated by indirect means (e.g. derivatization). This is because classical conformational analysis of the resulting 1,2-diboranes is not viable; in the (1)H NMR spectrum the relevant (1)H resonances are broadened by (11)B, and the occurrence of the products as oily compounds precludes X-ray crystallographic analysis. Herein, the crystalline sponge method is used to display the crystal structures of the diboronic esters formed from internal E and Z olefins, evidencing the stereospecific syn addition mechanism of the reaction, which is fully consistent with the prediction from DFT calculations.

Compressed Corannulene in a Molecular Cage.

Self-assembled coordination cages can be employed as a molecular press, where the bowl-shaped guest corannulene (C20H10) is significantly flattened upon inclusion within the hydrophobic cavity. This is demonstrated by the pairwise inclusion of corannulene with naphthalene diimide as well as by the dimer inclusion of bromocorannulene inside the box-like host. The compressed corannulene structures are unambiguously revealed by single-crystal X-ray analysis.

Cycloelatanene A and B: absolute configuration determination and structural revision by the crystalline sponge method

Cycloelatanene A and B are marine natural products first reported a few years ago. Their relative structures had been elucidated by an extensive NMR study and found to be epimers. However, their absolute configurations had not been established because they were isolated in only minute quantities as oily compounds. In this study, the complete structures of cycloelatanene A and B, including absolute configurations, were determined by the crystalline sponge method. The structure analysis confirmed the unique tricyclic structure involving a spiro[5.5]undecene skeleton. One stereogenic centre at C4 was revised as a result of this analysis. Since it only took 1–2 weeks to complete the experiments using the crystalline sponge method (guest-soaking followed by crystallographic analysis), this method is now highly recommended as a first port of call to achieve complete natural product structure elucidation.

A Tray-Shaped, PdII-Clipped Au3 Complex as a Scaffold for the Modular Assembly of [3×n] Au Ion Clusters†

A tray-shaped Pd(II)3Au(I)3 complex (1) is prepared from 3,5-bis(3-pyridyl)pyrazole by means of tricyclization with Au(I) followed by Pd(II) clipping. Tray 1 is an efficient scaffold for the modular assembly of [3×n] Au(I) clusters. Treatment of 1 with the Au(I)3 tricyclic guest 2 in H2O/CH3CN (7:3) or H2O results in the selective formation of a [3×2] cluster (1⋅2) or a [3×3] cluster (1⋅2⋅1), respectively. Upon subsequent addition of Ag(I) ions, these complexes are converted to an unprecedented Au3-Au3-Ag-Au3-Au3 metal ion cluster.

Application of the Crystalline Sponge Method to Revise the Structure of the Phenalenone Fuliginone

The structure of fuliginone was revised from a phenyl substituted phenalenone to a hydroxyl substituted phenalenone as a result of its re-purification via HPLC with subsequent NMR analysis together with an independent synthesis and analysis of the crystal structure, which was secured via the crystalline sponge method. On-flow High Performance Liquid Chromatography coupled to Nuclear Magnetic Resonance spectroscopy (HPLC-NMR) was employed to confirm the presence of the natural product in the plant extract and to monitor for any possible degradation or conversion of the compound.