Crystal structures of (±)-(1,5,6,7,10,11,13,14,15,16)-13-acet-oxy-16-benzyloxy-15-hy-droxy-7-meth-oxy-meth-oxy-3-oxo-11,15,18,18-tetra-methyl-2,4-dioxa-tetra-cyclo[12.3.1.0.0]octa-decan-10-yl benzoate and its 13-epimer.

The title compounds, CHO ( and ), are tetra-cyclic benzoates composed of a taxane ring with a fused dioxolane ring as the core skeleton. In compound , the five-membered dioxolane ring is essentially planar while the two cyclo-hexane rings and the cyclo-octane ring adopt chair and chair-chair forms, respectively, and there are three intra-molecular H⋯H short contacts. The corresponding ring conformations in are similar; however, one intra-molecular C-H⋯O inter-action and two H⋯H short contacts are observed, and the benzoyl and meth-oxy-methyl groups show orientational disorder.

Conjugate Position of Glucuronide and Sulfate in Piceatannol Derivatives Affects the Stability and Hydrolytic Resistance of the Conjugate in Biological Matrices.

Piceatannol, a stilbene compound, undergoes a comprehensive phase II metabolism mediated by UDP-glucuronosyltransferases (UGTs) and sulfotransferases (SULTs) in humans. Despite their well-documented beneficial effects on health, their detailed pharmacokinetic fate, including the metabolite structure and properties, is poorly understood. Thus, we determined the structure of seven glucuronides and six sulfates transformed from piceatannol and its methylated derivatives in recombinant yeast cells expressing UGTs or SULTs.

Cladoic Acid, an Anti- Polyketide from sp. TP-F2020.

A new polyketide, cladoic acid, was isolated from a fungus of the genus . The structure of the highly oxygenated -decalin ring with an all- triene side chain was elucidated by extensive spectroscopic analysis. The unique chair/twist-boat conformation of the -decalin core and the flexibility of the B-ring were demonstrated by computer-aided conformational analysis.

Synthesis of Macrolactone Core of -Formosalide A via Regioselective Ether Cyclization.

Formosalide A is a cytotoxic macrolide isolated from the dinoflagellate sp, whose structure is characterized by functionalized 5- and 6-membered ether rings embedded in the macrolactone and an all -tetraene side chain. Here, we report the synthesis of the macrolactone core of -formosalide A. Our approach is highlighted by the Au-mediated 6-- cyclization for the synthesis of the 6-membered ether ring, which proceeded in a highly regioselective manner.

Computational Study Focusing on a Comprehensive Conformational Analysis of Transition States for Aza-Spiro Ring Formations with -Alkoxyamides.

An accurate understanding of conformations in transition states is a critical piece in the theoretical analysis of complex molecular reactions. In this study, we investigated conformationally diverse transition states during intramolecular aza-spiro ring formation with an allylsilane moiety and -alkoxy iminium ion, a key reaction in the synthesis of fasicularin by Sato and Chida , and identified the origins of stereoselectivity of the cyclization. A large number of conformational isomers with forming C-C bonds were comprehensively analyzed using Cremer-Pople puckering parameters.

Isolation and structure determination of allopteridic acids A-C and allokutzmicin from an unexplored actinomycete of the genus Allokutzneria.

Two classes of new polyketides, allopteridic acids A-C (1-3) and allokutzmicin (4), were isolated from the culture extract of an actinomycete of the genus Allokutzneria. The structures of 1-4 were elucidated through the interpretation of NMR and MS analytical data. Compounds 1-3 possess the same carbon skeleton with pteridic acids but their monocyclic core structures are distinct from the spiro-bicyclic acetal structures of pteridic acids.

Krasilnikolides A and B and Detalosylkrasilnikolide A, Cytotoxic 20-Membered Macrolides from the Genus : Assignment of Anomeric Configuration by -Based Configuration Analysis.

A chemical investigation of strain RD003821, belonging to the underexplored actinomycetes genus , led to the discovery of three novel polyketides: two 20-membered glycomacrolides, krasilnikolides A () and B (), and an aglycone of , detalosylkrasilnikolide A (). A major challenge in the structure elucidation of was to determine the anomeric configuration of the α-l-6-deoxytalose (6dTal) unit, which was achieved by -based configuration analysis (JBCA) that incorporated anomeric carbon- and proton-specific two-bond C-H spin-spin coupling constants as diagnostic parameters. The updated criteria for the conformation/configuration assignment facilitated discrimination of three out of four stereochemical variants at the anomeric and the adjacent C2 positions, which expanded the scope of the JBCA method to determination of the anomeric configuration of aldohexopyranoses.

Cyclic enaminones and a 4-quinazolinone from an unidentified actinomycete of the family Micromonosporaceae.

Four novel cyclic enaminones, designated RD4123A-D (1-4), and a new 4-quinazolinone metabolite, RD4123E (5), were isolated from the culture extract of an unidentified actinomycete strain RD004123, which belongs to the family Micromonosporaceae. Structures of 1-5 were determined by spectroscopic analyses using NMR, MS, and electronic circular dichroism (ECD), combined with quantum chemical calculations of ECD and NMR chemical shifts and biosynthetic consideration. Compounds 1-5 showed weak to modest cytotoxicity against murine leukemia P388 cells, while being inactive against bacteria and fungi.

Bisprenyl naphthoquinone and chlorinated calcimycin congener bearing thiazole ring from an actinomycete of the genus Phytohabitans.

A bisprenyl naphthoquinone, phytohabinone (1), and a calcimycin congener with unusual modifications, phytohabimicin (2), were isolated from the culture extract of Phytohabitans sp. RD003013. The structures of 1 and 2 were determined by NMR and MS analyses, and the absolute configuration of 2 was established by using electronic circular dichroism (ECD) calculation.

Catellatolactams A-C, Plant Growth-Promoting Ansamacrolactams from a Rare Actinomycete of the Genus .

Catellatolactams A-C (-), three novel ansamacrolactams, were isolated from the culture extract of an underexplored rare actinomycete of the genus . Spectroscopic and spectrometric analyses by NMR and MS elucidated the structure of to be a lactamized pentaketide presumably extended on a 3-amino-5-hydroxybenzoic acid starter unit. Compounds and further received epoxidation and intramolecular cross-linking to incorporate a 2-indolinone unit, with a 3-amino-5-hydroxybenzoic acid pendant on .

Stereocontrolled Synthesis of C20-C26 and C20-C26 Fragments of Amphidinolide L.

Amphidinolide L is a cytotoxic macrolide isolated from marine symbiotic dinoflagellates of the genus . While its planar structure and the absolute stereochemistry of the C21-C26 part have been determined, six stereocenters have remained unassigned. Aiming at structure determination, we have developed a synthetic route to the C20-C26 and C20-C26 fragments via the Li-mediated stereocontrolled aldol reaction.

Marinoquinolones and Marinobactoic Acid: Antimicrobial and Cytotoxic -Dialkylbenzene-Class Metabolites Produced by a Marine Obligate Gammaproteobacterium of the Genus .

Chemical investigation of the culture extract of a marine obligate proteobacterium, sp. C17-8, isolated from scleractinian coral sp., led to the discovery of three new -dialkylbenzene-class metabolites, designated marinoquinolones A () and B () and marinobactoic acid ().

RCM approach to the CDE-tricyclic structure of nakiterpiosin.

A synthetic approach to the CDE-tricyclic structure of nakiterpiosin, a marine-derived antimitotic C-nor-D-homosteroid, is reported. The trans-disubstituted indanone was synthesized from a commercially available carboxylic acid in 9 steps, and the ring closing metathesis of the indanone constructed the trans-fused 5/6-membered ring system. The present approach enables the concise synthesis of the functionalized CDE-tricyclic structure, which will serve as a synthetic intermediate toward nakiterpiosin.

Kumemicinones A-G, Cytotoxic Angucyclinones from a Deep Sea-Derived Actinomycete of the Genus .

Chemical investigation of the fermentation products of a deep sea water-derived actinomycete, sp. KD439, identified seven new angucyclinones, designated as kumemicinones A-G (-), together with the known SF2315B and miaosporone E. NMR and MS spectroscopic analyses, combined with X-ray crystallography and quantum chemical calculations of NMR chemical shifts and electronic circular dichroism (ECD) spectra, uncovered the structures of new angucyclinones as regioisomers of SF2315B at the allyl alcohol unit ( and ), an epoxy ring-opened γ-hydroxy enone isomer (), a B/C-ring-rearranged product (), or dimers with a new mode of bridging (-), adding new structural variation to this antibiotic group.

Crystal structure of (+)-(1,5,6,7,10,11,16)-16-hy-droxy-7-(meth-oxy-meth-oxy)-11,15,18,18-tetra-methyl-3,13-dioxo-2,4-dioxa-tetra-cyclo[12.3.1.0.0]octa-dec-14-en-10-yl benzoate.

In the fused tetra-cyclic system of the title compound, CHO, the five-membered dioxolane ring adopts a twist conformation; the two adjacent C atoms deviate alternately from the mean plane of the other three atoms by -0.252 (6) and 0.340 (6) Å.

Total Synthesis of Paclitaxel.

The total synthesis of paclitaxel (Taxol) is described. Double Rubottom oxidation of the bis(silyl enol ether) derived from a tricarbocyclic diketone effectively installed a bridgehead olefin and C-5/C-13 hydroxy groups in a one-step operation. The novel Ag-promoted oxetane formation smoothly constructed the tetracyclic framework of paclitaxel.

Nomimicins B-D, new tetronate-class polyketides from a marine-derived actinomycete of the genus .

Three new tetronate-class polyketides, nomimicins B, C, and D, along with nomimicin, hereafter named nomimicin A, were isolated from the culture extract of sp AKA43 collected from floating particles in the deep-sea water of Sagami Bay, Japan. The structures of nomimicins B, C, and D were elucidated through the interpretation of NMR and MS analytical data, and the absolute configuration was determined by combination of NOESY/ROESY and ECD analyses. Nomimicins B, C, and D showed antimicrobial activity against Gram-positive bacteria, and , with MIC values in the range of 6.

Structure Determination, Biosynthetic Origin, and Total Synthesis of Akazaoxime, an Enteromycin-Class Metabolite from a Marine-Derived Actinomycete of the Genus .

A new enteromycin-class antibiotic, akazaoxime (), possessing an aldoxime functionality in place of -methyl nitronic acid, was isolated from the cultured extract of a marine-derived actinomycete of the genus , along with known A-76356 (). The structure of , including the absolute stereochemistry of three chiral centers, was established by comprehensive analysis of nuclear magnetic resonance (NMR) and mass spectrometry data coupled with magnetic anisotropy analysis of its phenylglycine methyl ester derivatives. The stereochemistry of , not determined previously, was proven to be the same as that of on the basis of the similarity of their NMR and specific rotation data.

TMKS8A, an antibacterial and cytotoxic chlorinated α-lapachone, from a sea slug-derived actinomycete of the genus Streptomyces.

TMKS8A (1), a new chlorinated α-lapachone derivative, along with five known related metabolites, A80915 C (2), SF2415B1 (3), chlorinated dihydroquinone 3 (4), SF2415B3 (5), and A80915 C (6), were identified from the culture extract of Streptomyces sp. TMKS8, which was isolated from a sea slug, Paromoionchis tumidus. The structure of 1 was determined by the analysis of NMR and MS spectral data, assisted by NMR chemical shift prediction using DFT-based calculation.

Pharmacokinetics and metabolism of cinnamic acid derivatives and flavonoids after oral administration of Brazilian green propolis in humans.

Brazilian green propolis (BGP) has chemical compounds from botanical origin that are mainly cinnamic acid derivatives (artepillin C, baccharin, and drupanin) and flavonoids (kaempferide and 6-methoxykaempferide). These compounds are expected to play an important role in the pharmacological activities of BGP. However, there is little known about the pharmacokinetics and metabolism of these compounds after oral administration of BGP.

Cyclopeptides from the Mushroom Pathogen Fungus .

Three new cyclopeptides with serial Phe residues were identified with the aid of HPLC-DAD analysis, from the culture broth of , a fungal pathogen causing mushroom cobweb disease. Cladoamides A () and B () have two consecutive -methylphenylalanine units in the destruxin class cyclic depsipentapeptide framework, while cladoamide C () has a three consecutive Phe motif in a cyclopentapeptide structure. Of these three cyclopeptides, showed potent autophagy-inducing activity at 10 μg/mL, comparable to a positive control, rapamycin.

A cyclopeptide and three oligomycin-class polyketides produced by an underexplored actinomycete of the genus .

Aside from the well-studied conventional actinomycetes such as , the less investigated genera of actinomycetes also represent a promising source of natural products. Genome mining indicated that members of the underexplored genus , from which no secondary metabolites have been reported to date, may harbor the biosynthetic machinery for the formation of novel natural products. The strain RD062863, that is available at a public culture collection, was obtained and subjected to metabolite analysis, which resulted in the discovery of a novel cyclopeptide, pseudosporamide (), along with three new oligomycin-class polyketides, pseudosporamicins A-C (-).

Computational Analysis of the Selective Formation of the C4α-C8' Bond in the Intermolecular Coupling of Catechin Derivatives.

Procyanidin B3 is a natural flavonoid composed of two catechins connected via a C4α-C8' bond. The couplings of catechin derivatives, promoted by Lewis acids, have been widely applied to the syntheses of procyanidin B3 and related flavonoids because the reactions construct the C4α-C8' bond in a highly stereo- and regioselective manner. However, the structural complexity of the catechin derivatives has complicated the exploration of a detailed mechanism for this selectivity.