Oxazaborolidine-catalyzed reductive parallel kinetic resolution of ketones from ß-nitro-azabicycles for the synthesis of chiral hypoestestatins 1, 2.

A novel approach for the synthesis of 13a-methyl tylophora alkaloids has been reported. The key features included two different synthetic pathways targeted at transforming the ß-nitro-azabicycle to the phenanthrene core. The successful steps involved the oxidation of the nitro-piperidine moiety to the corresponding α,ß-unsaturated ketone, and an oxidative biaryl coupling reaction for phenanthrene ring formation. Finally, the desired product was obtained via a formal reductive removal of the hydroxyl group. This methodology has been applied for the synthesis of 13a-methyl tylophora alkaloids in up to 65% yield over six steps from ß-nitro-azabicycles. Both natural and unnatural enantioenriched hypoestestatins 1 and 2, and related compounds were synthesized using parallel kinetic resolution of the CBS-oxazaborolidine-catalyzed reduction of racemic ketones to provide two separable diastereomeric alcohols in combined yields up to 91% and with high enantioselectvity (up to 89% ee). In addition, the catalytic asymmetric reduction to seco-hypoestestatins 1 and 2 has been reported for the first time. Thus, the ability to develop the racemic mixtures to both enatioenriched forms offers benefit for various biological assays in the future.

Metal-Free, One-Pot Cascade Annulation of 2-Pyrones in Water for the Synthesis of Peptidomimetics.

A one-pot, metal-free, double cyclization for the synthesis of bicyclic 2-pyridones as peptidomimetics was developed. In this process, the transformation of 2-pyrones bearing a tethered, homochiral α-amino acid started with the removal of the N-Boc protective group under acidic or neutral conditions at elevated temperature, followed by several key transformations, including cyclic enamine formation, decarboxylation or esterification, isomerization, and lactamization, to furnish bicyclic 2-pyridones in up to 98% yield with retention of the chirality at the α-carbon of the amino acid portion of the molecule. Exploration of the substrate scope revealed some selectivity between the decarboxylation and esterification pathways under thermal acidic conditions, while performing the reaction in boiling water yielded the decarboxylation products exclusively.

One-pot cascade synthesis of azabicycles via the nitro-Mannich reaction and N-alkylation.

A one-pot, metal-free process for the synthesis of azabicycles is developed. The key transformations involved a cascade of double intramolecular cyclizations via the nitro-Mannich reaction and N-alkylation, providing various ring systems of azabicycles in yields up to 81% and an isomeric ratio of 62 : 1. This approach offers considerable advantages in terms of the handling of small molecules, the flexibility to introduce a functionalized side chain, and gives direct access to various azabicycles.

3-Hydroxydihydrobenzofuran glucosides from Gnaphalium polycaulon.

A new 3-hydroxydihydrobenzofuran glucoside, gnaphaliol 9-O-ß-D-glucopyranoside (2), was isolated from the aerial parts of Gnaphalium polycaulon together with 1-{(2R*,3S*-3-(ß-D-glucopyranosyloxy)-2,3-dihydro-2-[1-(hydroxyl methyl)vinyl]-1-benzofuran-5-yl}-ethanone or gnaphaliol 3-O-ß-D-glucopyranoside (1), (Z)-3-hexenyl O-ß-D-glucopyranoside (3) and adenosine (4). The absolute configurations at C-2 and C-3 positions of compound 1 were determined to be 2R and 3R. The structures of these compounds were elucidated on the basis of their physical and spectroscopic data.

L-(-)-(N-trans-cinnamoyl)-arginine, an acylamino acid from Glinus oppositifolius (L.) Aug. DC.

An amino acid derivative, L-(-)-(N-trans-cinnamoyl)-arginine, was isolated from the whole plant of Glinus oppositifolius (L.) Aug. DC. along with kaempferol 3-O-galactopyranoside, isorhamnetin 3-O-beta-D-xylopyranosyl-(1-->2)-beta-D-galactopyranoside, vitexin, vicenin-2, adenosine and L-phenylalanine. The structure determinations were based on analyses of chemical and spectroscopic methods.

Phenylethanoid and flavone glycosides from Ruellia tuberosa L.

A new phenylethanoid glycoside, isocassifolioside (8), and two new flavone glycosides, hispidulin 7-O-α-L-rhamnopyranosyl-(1'″ → 2″)-O-ß-D-glucuronopyranoside (11) and pectolinaringenin 7-O-α-L-rhamnopyranosyl-(1'″ → 2″)-O-ß-D-glucuronopyranoside (12) were isolated from the aerial portions of Ruellia tuberosa L., together with verbascoside (1), isoverbascoside (2), nuomioside (3), isonuomioside (4), forsythoside B (5), paucifloside (6), cassifolioside (7), hispidulin 7-O-ß-D-glucuronopyranoside (9) and comanthoside B (10). The structure elucidations were based on analyses of chemical and spectroscopic data including 1D- and 2D-NMR. The isolated compounds 1-12 exhibited radical scavenging activity using ORAC assay.

Unprecedented furan-2-carbonyl C-glycosides and phenolic diglycosides from Scleropyrum pentandrum.

Five unprecedented furan-2-carbonyl C-glycosides, scleropentasides A-E, and two phenolic diglycosides, 4-hydroxy-3-methoxybenzyl 4-O-ß-D-xylopyranosyl-(1→6)-ß-D-glucopyranoside and 2,6-dimethoxy-p-hydroquinone 1-O-ß-D-xylopyranosyl-(1→6)-ß-d-glucopyranoside, were isolated from leaves and twigs of Scleropyrum pentandrum together with potalioside B, luteolin 6-C-ß-D-glucopyranoside (isoorientin), apigenin 8-C-ß-D-glucopyranoside (vitexin), apigenin 6,8-di-C-ß-D-glucopyranoside (vicenin-2), apigenin 6-C-α-L-arabinopyranosyl-8-C-ß-D-glucopyranoside (isoschaftoside), apigenin 6-C-ß-D-glucopyranosyl-8-C-ß-D-xylopyranoside, adenosine and l-tryptophan. Structure elucidations of these compounds were based on analyses of chemical and spectroscopic data, including 1D and 2D NMR. In addition, the isolated compounds were evaluated for their radical scavenging activities using both DPPH and ORAC assays.

Unusual glycosides of pyrrole alkaloid and 4'-hydroxyphenylethanamide from leaves of Moringa oleifera.

Glycosides of pyrrole alkaloid (pyrrolemarumine 4″-O-α-L-rhamnopyranoside) and 4'-hydroxyphenylethanamide (marumosides A and B) were isolated from leaves of Moringa oleifera along with eight known compounds; niazirin, methyl 4-(α-L-rhamnopyranosyloxy)benzylcarbamate, benzyl ß-D-glucopyranoside, benzyl ß-D-xylopyranosyl-(1→6)-ß-D-glucopyranoside, kaempferol 3-O-ß-D-glucopyranoside, quercetin 3-O-ß-D-glucopyranoside, adenosine and L-tryptophan. Structure elucidations were based on analyses of chemical and spectroscopic data including 1D- and 2D-NMR.

Guanidinium ylide mediated aziridination: identification of a spiro imidazolidine-oxazolidine intermediate.

We successfully isolated a spiro imidazolidine-oxazolidine intermediate in the reaction of guanidinium ylide mediated aziridination using alpha-bromocinnamaldehyde. X-ray crystallographic analysis unambiguously revealed that the stereogenic centers of the spiro intermediate were in a trans configuration. The role of the spiro compound as an intermediate in the aziridination reaction was confirmed by observation of its smooth chemical conversion into aziridine products.

Chirality transfer from guanidinium ylides to 3-alkenyl (or 3-alkynyl) aziridine-2-carboxylates and application to the syntheses of (2R,3S)-3-hydroxyleucinate and D-erythro-sphingosine.

[Reaction: see text]. Reaction of chiral guanidinium ylides with alpha,beta-unsaturated aldehydes gives 3-(alpha,beta-unsaturated) aziridine-2-carboxylates in high diastereo- and enantioselectivities (up to 93% diastereomeric excess and 98% enantiomeric excess). 3-(1-methylvinyl)- and 3-[(E)-pentadec-1-enyl]aziridine-2-carboxylates were successfully employed to prepare (2R,3S)-3-hydroxyleucinate and d-erythro-sphingosine, respectively.

Facile characterization of polymer-supported reagents using cross polarization magic angle spinning method in solid state 13C-NMR.

Polymer-supported (PS) reagents can be easily characterized using a cross polarization magic angle spinning method in solid state (13)C-NMR. The technique was applied to the characterization of PS-dimethylimidazolidinone, analogue to potential heterogeneous dehydrating agent.