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Fungal meroterpenoids are a diverse group of hybrid natural products with impressive structural complexity and high potential as drug candidates. In this work, we evaluate the promiscuity of the early structure diversity-generating step in fungal meroterpenoid biosynthetic pathways: the multibond-forming polyene cyclizations catalyzed by the yet poorly understood family of fungal meroterpenoid cyclases. In total, 12 unnatural meroterpenoids were accessed chemoenzymatically using synthetic substrates. Their complex structures were determined by 2D NMR studies as well as crystalline-sponge-based X-ray diffraction analyses. The results obtained revealed a high degree of enzyme promiscuity and experimental results which together with quantum chemical calculations provided a deeper insight into the catalytic activity of this new family of non-canonical, terpene cyclases. The knowledge obtained paves the way to design and engineer artificial pathways towards second generation meroterpenoids with valuable bioactivities based on combinatorial biosynthetic strategies.

Genome mining, an effective approach to natural product discovery, often requires large-scale cultivation (several to dozens of liters). Here, we demonstrate that the crystalline sponge method significantly reduces the cultivation scale as the method requires only a microgram quantity of an analyte. Prior to the NMR study, we directly addressed the X-ray structure of a natural product from a terpene synthase, which was heterologously expressed by only a 25-mL scale cultivation. [ABSTRACT FROM AUTHOR]

Methods for precisely constructing a β‐sheet assembly with number‐defined strands in solution remains quite limited due to its intense aggregation property. Here, we report the precise construction of a four‐stranded anti‐parallel β‐sheet by utilizing a non‐covalent approach. This was achieved by folding and assembly of Ag+ and a pentapeptide (1) with the Ala‐D3pa‐Gly‐3pa‐Val (3pa: β‐(3‐pyridyl)‐alanine) sequence, which was designed to form an interlocking Ag2(1)2 ring through metal cross‐linking of the side chains. NMR analyses and X‐ray crystallographic studies characterized the structure of the discrete β‐sheet assembly as well as the remarkable structural selectivity in terms of strands’ number, orientation and the sheet type. [ABSTRACT FROM AUTHOR]

Experimental and theoretical evidence is reported for a rare type I dyotropic rearrangement involving a [1,2]-alkene shift, leading to the regio- and stereospecific ring contraction of bromocycloheptenes. This reaction occurs under mild conditions, with or without a Lewis acid catalyst. DFT calculations show that the reaction proceeds through a nonclassical carbocation-anion pair, which is crucial for the low activation barrier and enantiospecificity. The chiral cyclopropylcarbinyl cation may be a transition state or an intermediate, depending on the reaction conditions.

Arene‐formaldehyde condensation is a versatile reaction for producing various oligomeric/polymeric materials. However, the precise control of oligomerization degree is still challenging because the starting materials and intermediates have similar reactivities. Here, we demonstrate the selective synthesis of a methylene‐bridged arene trimer using the confined cavity of a coordination cage. The limited space of the cavity prevents unregulated polymerization. The confinement effect for the kinetic protection is also demonstrated by the subsequent site‐selective iodination of the trimer product within the cage. [ABSTRACT FROM AUTHOR]

The Industries need techniques for the rapid structure analysis of amino acid derivatives. The amino acid derivatives are sometimes produced as impurities in the industrial production processes, and cause toxicity problems. Herein, we report the crystalline sponge (CS) method analysis of variety of amino acids using a formyl group installed CS crystal. Most amino acids possess a primary amino group, which can form Schiff‐base with the formyl group under mild conditions. Thus, the formyl group installed CS crystal can efficiently capture the amino acids via Schiff‐base formation. We successfully analyzed derivatives of 18 proteogenic amino acids, 6 non‐proteogenic amino acids, and 4 dipeptides using the formyl group installed CS. We thus believe that the protocols shown in this study would serve the need of the industries. [ABSTRACT FROM AUTHOR]

Numerous indole alkaloids such as the iboga‐ and aspidosperma‐type are believed to be biosynthesized via a common hypothetical intermediate, dehydrosecodine. The highly reactive nature of dehydrosecodine‐type compounds has hampered their isolation and structural elucidation. In this study, we achieved the first X‐ray structural determination of a dehydrosecodine‐type compound by integrating synthetic optimization of the reactivity and stabilizing the fragile molecule by encapsulation into a supramolecular host. Formation of a 1 : 1 complex of the dehydrosecodine‐type labile guest bearing both vinyl indole and dihydropyridine units with the host was observed. This integrated approach not only provides insights into the biosynthetic conversions but also allows stabilization and storage of the reactive and otherwise short‐lived intermediate within the confined hydrophobic cavity. [ABSTRACT FROM AUTHOR]

Author(s): Daishi Fujita (corresponding author) [1, 2, 3]; Yoshihiro Ueda [1, 3]; Sota Sato [4, 5]; Nobuhiro Mizuno [6]; Takashi Kumasaka [6]; Makoto Fujita (corresponding author) [1, 3] Rational control [...]

The patient is a 60-year-old female with a history of multiple times of recurrences of an esophageal diverticulum. She was referred for a diagnosis of persistent dysphagia and vomiting. Balloon dilation did not improve the symptoms; thus, she was referred for surgery. Esophageal fluoroscopy revealed a 5 cm diverticulum. There was no significant change in the size before and after dilation. Gastrointestinal endoscopy revealed a diverticulum in the lower esophagus, with a residue accumulation. The esophagus directly below the diverticulum was narrowed. The patient was diagnosed with recurrent lower esophageal diverticulum and underwent surgery. The operative findings showed poor coloration of the gastric fundus surrounding operated before by Nissen's method, so the patient underwent lower esophagogastric resection and interstitial jejunal reconstruction. The postoperative course was uneventful and discharged on the 19th day. She is 6 years postoperatively and gained six kg compared to her preoperative weight. She has remained in excellent health. [ABSTRACT FROM AUTHOR]