Vanchrobactin: absolute configuration and total synthesis

The stereochemistry of vanchrobactin, a siderophore produced by the bacterial fish pathogenVibrio anguillarum serotype O2, was elucidated by chiral capillary electrophoresis analysis and total synthesis as N-[N′-(2,3-dihydroxybenzoyl)-d-arginyl]-l-serine.     

Enantioselective, chemoenzymatic synthesis, and absolute configuration of the antioxidant (−)-gloeosporiol

The natural antioxidant (−)-gloeosporiol, isolated as a peracetylated derivative from a culture of the fungus Colletotrichum gloeosporioides, has been enantioselectively prepared from 3,4-dihydroxybenzaldehyde by means of a chemoenzymatic synthesis. The key intermediate was obtained by resolution with a lipase from Pseudomonas cepacia. Its stereochemistry, initially assigned as R, according to the Kazlaukas empirical rule for secondary alcohols, was independently confirmed by NMR and chirooptic methods. This, in turn, allowed the assignment of compound (−)-1 as (−)-(2S,3R,4R)-2-(3′,4′dihydroxyphenyl)tetrahydrofuran-3,4-diol.     

Structure and absolute configuration of penicilliumine,a new alkaloid from Penicillium commune 366606

Penicilliumine (1), a new structure was isolated from the fermentation Penicillium commune 366606, a marine-derived fungus isolated from the sea water collected at Qingdao, China. HPLC chiral separation of 1 afforded two enantiomers (−)-penicilliumine and (+)-penicilliumine, respectively. The structure of 1 was established by comprehensive spectroscopic data, and single-crystal X-ray diffraction. The absolute configuration of enantiomers was determined by quantum mechanical computation of electronic circular dichroism (ECD).     

Asymmetric synthesis of a diastereomer of the structure proposed for amphidinolide A and the determination of its absolute configuration

An asymmetric synthesis of a diastereomer (2) of the structure (1) proposed for amphidinolide A, a cytotoxic macrolide from the cultured dinoflagellate Amphidinium sp., has been accomplished. The absolute configuration of amphidinolide A was established as 3 from comparison of NMR data, HPLC analysis, and [α]_D values of amphidinolide A, and comparison with the synthetic diastereomers 2 and 3, the latter of which was synthesized previously by Trost's group.     

Enantioselective synthesis and absolute configuration of the sex pheromone of Hedypathes betulinus (Coleoptera: Cerambycidae)

The male-produced sex pheromone of Hedypathes betulinus was identified as a mixture of (E)-6,10-dimethyl-5,9-undecadien-2-one (geranylacetone) (1) and its respective alcohol (2) and acetate (3). Kinetic resolution of alcohol (2) promoted by CAL-B in organic media provided both, (R)-(−)-(E)-6,10-dimethyl-5,9-undecadien-2-yl acetate (3) and (S)-(+)-(E)-6,10-dimethyl-5,9-undecadien-2-ol (2) in high enantiomeric purity. Comparative GC analysis using a chiral column revealed the natural constituents as being (R)-(3) and a mixture of (R)- and (S)-(2) in a ratio of 82.3% and 17.6%, respectively.     

Diverse prieurianin-type limonoid derivatives from the fruits of Aphanamixis grandifolia and their absolute configuration determination

Twenty-five new highly oxygenated prieurianin-type limonoids, zaphaprinins A–Y (1–25), were isolated from the fruits of Aphanamixis grandifolia. Their structures were elucidated by extensive spectroscopic analyses. Absolute configurations for the key structures like 1 were assigned by a comprehensive method, such as comparing the calculated electronic circular dichroism (ECD) with the experimental one, single-crystal X-ray and Mosher ester method were also involved for other compounds' study. The solid data from X-ray diffraction allowed revision of the stereochemistry of the C₁–C₁₄ tetrahydropyran ring-type limonoid. The insecticidal activities of all the limonoids were evaluated.     

Determination of absolute configuration of C14−C23 fragment in symbiodinolide

The degradation product C14−C23 2 was obtained using ethenolysis with the 2nd-generation Hoveyda-Grubbs catalyst from 62-membered lactone in symbiodinolide (1). The absolute configurations of three chiral centers in fragment 2 were assigned as 17R, 18R, and 21R by a combination of J-based configuration analysis and the Mosher-Riguera method.     

Assignment of the absolute configuration of blasticidin A and revision of that of aflastatin A

The absolute configuration of blasticidin A, a strong inhibitor of aflatoxin production by Aspergillus parasiticus, was assigned by adding the data of relative configurations at its diol and pentaol moieties to previously known stereochemistry. Similarity of the NMR data of blasticidin A to those of aflastatin A allowed us to revise the stereochemistry of the diol and pentaol moieties of aflastatin A.     

Synthesis and assignment of the absolute stereochemistry of (+)-hemifistularin 3

The first total synthesis of the marine natural product (+)-hemifistularin 3 in enantiomerically pure form was accomplished by using the amide forming reaction of (+)-spiroisoxazoline ester with the (+)-octopamine derivative. The stereodivergent strategy employed in this effort enabled the assignment of the absolute configurations at the three stereogenic centers in (+)-hemifistularin 3.     

Isolation and absolute configuration determination of alkaloids from Pandanus amaryllifolius

Seven new alkaloids belonging to three typical classes, isolated from an ethanolic extract of Pandanus amaryllifolius, were applied to establish the models in structural elucidation. The first type [pandanusines A and B (1 and 2)] was applied to alkaloids with a diazaspirocyclic ring system. The absolute stereochemistry of aminal carbon is determined by analysis of J-based configuration analysis and circular dichroism spectroscopy, which has never been revealed before. The second type [pandalizines C–E (3–5)], the stereochemistry of unusual indolizinone with chiral hydroxyl substitutions were determined by circular dichroism spectroscopy and vibrational circular dichroism experiments. The last type [norpandamarilactonines C and D (6 and 7)], a comparing model in determination of diastereomers of pyrrolidinyl α,β-unsaturated γ-lactone alkaloids was established. Our study provides solutions for a challenging subject in stereochemistry determination for three different types of Pandanus alkaloids.     

The absolute configuration determination of naturally occurring diacetylenic spiroacetal enol ethers from Artemisia lactiflora

Six new naturally occurring diacetylenic spiroacetal enol ethers, Lactiflodiynes A-F (1-6), together with five known congeners (7-11), were isolated from the whole plant of Artemisia lactiflora (Compositae). The structures were elucidated by extensive spectroscopic methods, X-ray crystallography, chemical transformations, and CD. The absolute configuration of Lactiflodiyne A (1) was determined to be 2R, 5S, 6S, and 7R by an X-ray crystallographic diffraction experiment using Mo Kα radiation with the absolute parameter of 0.01(8). In combination with CD, the absolute configurations of compounds 2-11 were confirmed by chemical transformations using 1 as the starting material.     

Absolute configuration and antibiotic activity of neosartorin from the endophytic fungus Aspergillus fumigatiaffinis

Neosartorin (1) was isolated from the endophytic fungus Aspergillus fumigatiaffinis. The absolute configuration of 1, including both axial and central chirality elements, was established as (aR,5S,10R,5′S,6′S,10′R) for the first time on the basis of its electronic circular dichroism (ECD) spectra aided with TDDFT–ECD calculations. Neosartorin (1) exhibited substantial antibacterial activity against a broad spectrum of Gram-positive bacterial species including staphylococci, streptococci, enterococci, and Bacillus subtilis with minimal inhibitory concentrations in the range of 4–32 μg/mL. When the toxicity of 1 against eukaryotic cells was measured using a panel of different cancer cell lines such as HELA and BALB/3T3, the average IC₅₀ values exceeded 32 μg/mL.     

Structure determination and absolute configuration of cannabichromanone derivatives from high potency Cannabis sativa

Three new cannabichromanone derivatives were isolated from high potency cannabis, along with the known cannabichromanone. Full spectroscopic data, including the use of electronic circular dichroism and Mosher ester analysis to determine the absolute configuration of these compounds, are reported. All isolates were tested for antimicrobial, antimalarial, antileishmanial, and anti-oxidant activities.     

Synthesis and absolute configuration of annuionone A

Synthesis of both enantiomers of annuionone A (1), an allelopathic agent isolated from Helianthus annuus (sunflower), was accomplished. The absolute configuration of the naturally occurring 1 was determined to be 1S,5R,8R.     

Synthesis of cordiaquinone J and K via B-alkyl Suzuki-Miyaura coupling as a key step and determination of the absolute configuration of natural products

A versatile methodology for the synthesis of various terpenoids via B-alkyl Suzuki-Miyaura coupling as a key step is established. Synthesis of cordiaquinone J and K, new antifungal and larvicidal meroterpenoids, was achieved by using this methodology. The absolute configurations of cordiaquinone J and K were confirmed by the synthesis.     

First synthesis and absolute configuration of decaturin D

The first synthesis of (+)-decaturin D (1), an antiinsectant diterpenoid isolated from Penicillium thiersii, was accomplished by employing our original spiro-cyclization reaction as the key step. The absolute configuration of the naturally occurring 1 was determined.     

Structure and absolute configuration of 3-alkylpiperidine alkaloids from an Indonesian sponge of the genus Halichondria

Chemical analysis of an Indonesian sponge sample has provided three new 3-alkylpiperidine alkaloids, tetradehydrohaliclonacyclamine A, its mono-N-oxide derivative, and a 2-epi isomer. The absolute structure of tetradehydrohaliclonacyclamine A has been established by X-ray crystallography from anomalous dispersion effects using Cu radiation, which determined that the absolute configuration is 2S, 3S, 7S, 9S while an HPLC study revealed that the alkaloid is enantiomerically pure.     

The first synthesis and absolute configuration of glaucescenolide

The first synthesis of glaucescenolide (1), a cytotoxic sesquiterpene isolated from the liverwort, Schistochila glaucescens, was achieved by starting from 2,2,6-trimethylcyclohexanone (2). The absolute configuration of the naturally occurring 1 was confirmed as 5S,7S,10R.     

Nortriterpenoids from Schisandra chinensis and their absolute configurational assignments by electronic circular dichroism study

Twelve new nortriterpenoids, namely wuweizidilactones J–P (1–7), schindilactones I–K (8–10), preschisanartanin N (11), and schisdilactone J (12), as well as 23 known analogues, were isolated from the leaves and stems of Schisandra chinensis. The absolute configurations of 1 and 11 were established by calculated electronic circular dichroism (ECD) spectra and that of 7 was confirmed by single-crystal X-ray diffraction. The absolute configurations of 2–6, 8, and 9 were determined by an empirical comparison of their experimental ECD spectra with that of 1. It is the first time that the ECD spectra of 18(13→14)-abeo-schiartane-, 18-norschiartane-, and schisanartane-type nortriterpenoids possessing an α,β-unsaturated-γ-lactone moiety are presented, this method providing an alternative means of obtaining absolute configurational assignments for these types of nortriterpenoids. All isolates were evaluated for their anti-acetylcholinesterase and anti-butyrylcholinesterase activities, and compounds 8, 13, 23, and 31 show anti-acetylcholinesterase activity at concentrations of 50 μM, with 12.7, 10.7, 16.6, and 32.1% inhibition, respectively.