Genome Mining-Based Discovery of Pyrano[2,3-]pyrrole Type Natural Products Possessing Alkyl Side Chain with Branched Methyl Groups.

Genome mining of polyketide synthase-nonribosomal peptide synthetase (PKS-NRPS) in fungal endophyte strain BRIP 39872 identified seven new natural products (olumilides A-D, D1, D1', D2) with pyrano[2,3-]pyrrole scaffolds and their biosynthetic precursor preolumilide. Unlike known congeners, such as curvupallides, olumilides possess alkyl side chains with branched methyl groups and threonine-derived core scaffolds. Absolute configurations were determined by microED and ECD simulations, providing valuable information for further research focusing on the stereochemistry of PKS-NRPS reactions.

Expanding the Diversity of the Terpene Skeleton and Structure through Identification of Noncanonical Class IE and IF Terpene Synthase-Formed Products.

Noncanonical class IE and IF terpene synthases have recently been discovered from bacterial genomes through the nonsequence-similarity-based method: protein-structural-model-based genome mining. This study identified the class IE product as a new diterpene comprising the first hydrocarbon skeleton among all terpenoids. The skeleton with a 6/6/6-fused tricyclic structure and six methyl groups could be synthesized through an unprecedented terpene-forming reaction.

Stereoisomer library prepared controlled radical polymerization: isolation, structural identification and discovery of stereospecific gelation behaviour of tri(N-phenyl acrylamide).

The construction of stereoisomer libraries is essential for designing, maximizing, and tuning the biological, self-assembly, and photoelectromagnetic properties of optically active molecules. In this study, a stereoisomer library consisting of all eight stereoisomers of a vinyl oligomer, a trimer of phenyl acrylamide (tri(PAAm)), was prepared by a one-pot controlled radical polymerization reaction followed by two-step column chromatography. Tacticity of each isomer, , the relative stereochemistry of three chiral centers within tri(PAAm), was assigned using proton nuclear magnetic resonance (H-NMR) and circular dichroism (CD) spectra.

Enantioselective Synthesis of Axially Chiral 1,8-Diarylnaphthalenes by Rh-Catalyzed [2 + 2 + 2] Cycloaddition and Evaluation of Their Chiroptical Properties.

Intermolecular [2 + 2 + 2] cycloaddition of 1-alkynyl-8-arylnaphthalenes with 1,6-diynes proceeded in the presence of Rh-chiral BINAP derivative catalysts to give axially chiral 1,8-diarylnaphthalenes in excellent yields along with up to perfect enantioselectivity. As the aryl moiety, we could introduce 1-pyrenyl and (dibenzo)carbazolyl groups in addition to substituted phenyl ones. 1-Aryl-8-(1-pyrenyl)naphthalenes exhibited high fluorescence quantum yields (up to Φ = 0.

Asymmetric Synthesis of Noradamantane Scaffolds via Diphenylprolinol Silyl Ether-Mediated Domino Michael/Epimerization/Michael (or Aldol)/1,2-Addition Reactions.

Topologically unique chiral noradamantanes are synthesized using a diphenylprolinol silyl ether-mediated domino Michael/epimerization/Michael/1,2-addition or Michael/epimerization/aldol/1,2-addition reaction with excellent enantioselectivity in a single reaction vessel. Three carbon-carbon bonds are formed, and six chiral centers, including one all-carbon quaternary center, are generated, five of which are fully controlled. These functionalized noradamantanes are 3D, cage-like molecules that can serve as valuable chiral building blocks for drug design.

Discovery and Theoretical Studies of Nonenzymatic Polyketide Dimerizations of Chaetophenols.

Nonenzymatic reactions sometimes construct complex structures observed in natural products, showing us unique chemical reactions. In our exploration of natural products, we identified a novel type of isochromene-derived polyketide dimer with a 6/6/6/6/6 five-ring system from along with several new related polyketides. We demonstrated that isochromene and its oxidized derivative undergo nonenzymatic dimerization under acidic conditions to give .

Scalable preparation of furanosteroidal viridin, β-viridin and viridiol from Trichoderma virens.

Viridin and viridiol, along with wortmannin, metabolized by filamentous fungus Trichoderma virens, are identical furanosteroids with high-potent inhibitory activity towards phosphatidylinositol 3-kinase (PI3K) that associates the growth of tumor cells. Therefore, structure-activity relationship study (SAR) of these furanosteroids contributes to the development of novel drugs. However, rational supply methods have not been established yet.

Computational Study on the Conformational Flexibility-Mediated Intramolecular Oxidative Spirocyclization of Procyanidin B4.

Procyanidins, found widely in foods and beverages, are prone to oxidation, yet the chemical structures of their oxidation products and the mechanisms involved remain unclear. Herein, we report that the conformation of procyanidin B4 influences its oxidation products and their stereochemistry. Eight spirocyclized oxidation products were obtained from procyanidin B4 and classified as - or -forms based on the configuration of the spiro carbons.

Raman optical activity study of deuterated sugars: deuterium labelling as a tool for structural analysis.

Structural analyses using Raman optical activity (ROA) spectroscopy conventionally rely on vibrational signals in the fingerprint region ranging from 100 to 1800 cm. Use of deuterium labelling to observe ROA signals in the C-D stretching region provides additional information about a local structure of large molecular systems. So far, the potential of C-D stretching ROA signals for structural analysis has rarely been explored.

Structural-model-based genome mining can efficiently discover novel non-canonical terpene synthases hidden in genomes of diverse species.

Non-canonical terpene synthases (TPSs) with primary sequences that are unrecognizable as canonical TPSs have evaded detection by conventional genome mining. This study aimed to prove that novel non-canonical TPSs can be efficiently discovered from proteins, hidden in genome databases, predicted to have 3D structures similar to those of class I TPSs. Six types of non-canonical TPS candidates were detected using this search strategy from 268 genome sequences from actinomycetes.

Determination of N-centered stereochemistry in N22-methylated chlorophyll-a derivatives and their epimer-dependent optical spectra.

An N-centered epimeric mixture of chlorophyll-a derivatives methylated at the inner nitrogen atom was separated by reverse-phase high-performance liquid chromatography. Circular dichroism (CD) spectroscopic analyses of the epimerically pure N22-methyl-chlorins revealed that the minor first-eluted and major second-eluted stereoisomers were (22S)- and (22R)-configurations, respectively. Their visible absorption and CD spectra in solution were dependent on the N22-stereochemistry.

Isolation and Structure Determination of -OPDA-α-Monoglyceride from .

-12-oxo-Phytodieneoic acid-α-monoglyceride () was isolated from . The chemical structure of was elucidated based on exhaustive 1D and 2D NMR spectroscopic measurements and supported by FDMS and HRFDMS data. The absolute configuration of the -OPDA moiety in was determined by comparison of H NMR spectra and ECD measurements.

Dopamine-Derived Guanidine Alkaloids from a Didemnidae Tunicate: Isolation, Synthesis, and Biological Activities.

Mellpaladines A-C () and dopargimine () are dopamine-derived guanidine alkaloids isolated from a specimen of Palauan Didemnidae tunicate as possible modulators of neuronal receptors. In this study, we isolated the dopargimine derivative 1-carboxydopargimine (), three additional mellpaladines D-F (), and serotodopalgimine (), along with a dimer of serotonin, 5,5'-dihydroxy-4,4'-bistryptamine (). The structures of these compounds were determined based on spectrometric and spectroscopic analyses.

Photoinduced dual bond rotation of a nitrogen-containing system realized by chalcogen substitution.

Photoinduced concerted multiple-bond rotation has been proposed in some biological systems. However, the observation of such phenomena in synthetic systems, in other words, the synthesis of molecules that undergo photoinduced multiple-bond rotation upon photoirradiation, has been a challenge in the photochemistry field. Here we describe a chalcogen-substituted benzamide system that exhibits photoinduced dual bond rotation in heteroatom-containing bonds.

Amoxetamide A, a new anoikis inducer, produced by combined-culture of Amycolatopsis sp. and Tsukamurella pulmonis.

Cancer cells including colorectal cancer cells are resistant to anoikis, an anchorage-independent programmed death, which enables metastasis and subsequent survival in a new tumor microenvironment. In this study, we identified a new anoikis inducer, amoxetamide A (1) with a β-lactone moiety, that was produced by combined-culture of Amycolatopsis sp. 26-4 and mycolic acid-containing bacteria (MACB) Tsukamurella pulmonis TP-B0596.

Vibrational circular dichroism spectroscopy in the C-D, XY, and XYZ stretching region.

Vibrational circular dichroism (VCD) spectroscopy is a powerful technique for structural analysis of chiral molecules, but information available from VCD spectra of large molecular systems can be limited by severe overlap of vibrational bands. While common chiral molecules do not absorb in the 1900-2400 cm region, observation of VCD signals in this spectrally-isolated region is possible for molecules containing C-D, XY, and XYZ chromophores. Thus, a strategic introduction of these chromophores to a target molecule may produce VCD signals informative for molecular structures.

Scope and limitations of absolute configuration determination of allenic natural products using the CCC stretching VCD signal.

The allene functional group in natural products isolated so far exists in a non-racemic form, but its axial chirality is difficult to elucidate. Allenes exhibit a characteristic antisymmetric CCC stretching mode at around 1950 cm, and their VCD properties have not been studied in detail. This work, for the first time, applied VCD spectroscopy to allenic natural products and allenic molecules with other asymmetric centers focusing on the antisymmetric CCC stretching mode.

Total Synthesis, Absolute Configuration, and Phytotoxic Activity of Foeniculoxin.

Foeniculoxin is a major phytotoxin produced by Italian strains of Phomopsis foeniculi. The first total synthesis is described utilizing the ene reaction and Sonogashira cross-coupling reaction as key steps. The absolute configuration of the C6' was determined using chiral separation and an advanced Mosher's method.

Stereoselective Construction of Fluorinated Quaternary Stereogenic Centers via an Organocatalytic Asymmetric -Selective Diels-Alder Reaction in the Presence of Water.

A catalytic, asymmetric Diels-Alder reaction of α-fluoro α,β-unsaturated aldehydes and cyclopentadiene was developed using diarylprolinol silyl ether as an organocatalyst. The reaction proceeds in toluene with trifluoroacetic acid as an additive (condition A). Perchloric acid salt of diarylprolinol silyl ether also promotes the reaction using water as a reaction medium (condition B).

Stereostructural analysis of flexible oxidized fatty acids by VCD spectroscopy.

Oxidation of polyunsaturated fatty acids produces various oxidized lipids whose absolute configuration (AC) and conformations are difficult to analyze due to their flexibility. Through studies on hydroxy fatty acids, lipid hydroperoxides, and lipid epoxides, this work demonstrates the effectiveness of VCD spectroscopy to elucidate their AC and conformational preferences.

Control of Reactions of Pyruvates by Catalysts: Direct Enantioselective Mannich Reactions of Pyruvates Catalyzed by Amine-based Catalyst Systems.

Enantioselective Mannich reactions of pyruvates catalyzed by amine-based catalyst systems, in which pyruvates act as nucleophiles, are reported. The reactions of pyruvates and cyclic sulfonylimines afforded the desired Mannich products, including those bearing tetrasubstituted carbon centers, in high yields with high enantioselectivities in most cases. The selection of the acid used in the amine-based catalyst system was key for the formation of the Mannich products with high enantioselectivities.

Deuterium labelling to extract local stereochemical information by VCD spectroscopy in the C-D stretching region: a case study of sugars.

Stereochemical elucidation of molecules with multiple chiral centers is difficult. Even with VCD spectroscopy, excluding all but one diastereomeric structural candidate is challenging because the stereochemical inversion of one chiral center among many centers does not always result in noticeable differences in their VCD spectra. This work demonstrates that the introduction of a suitable VCD chromophore with absorption in the 2300-1900 cm region can be used for extracting local stereochemical information and for the stereochemical assignment of the C-1 position of various sugars as a case study.

Exploration of chromophores for a VCD couplet in a spectrally transparent infrared region for biomolecules.

Interactions of two chromophores such as carbonyl groups yield a strong VCD couplet that reflects the molecular structures. The use of VCD couplets for biomacromolecular structural studies has been hampered by severe signal overlap caused by numerous functional groups that originally exist in biomacromolecules. Nitrile, isonitrile, alkyne, and azido groups show characteristic IR absorption in the 2300-2000 cm region, where biomolecules do not strongly absorb.

Enantiodivergent One-Pot Synthesis of Axially Chiral Biaryls Using Organocatalyst-Mediated Enantioselective Domino Reaction and Central-to-Axial Chirality Conversion.

Enantiodivergent one-pot synthesis of biaryls was developed using a catalytic amount of a single chiral source. A domino organocatalyst-mediated enantioselective Michael reaction and aldol condensation provided centrally chiral dihydronaphthalenes with excellent enantioselectivity, from which an enantiodivergent chirality conversion from central-to-axial chirality was achieved. Both enantiomers of biaryls were obtained with excellent enantioselectivity.