Inokosterone, an insect metamorphosing substance from Achyranthes fauriei : Absolute configuration and synthesis

Inokosterone, a phytoecdysone isolated from Achyranthes fauriei (Amaranthaceae), has been partially acetylated to give the 2,26-diacetate (4) which has been converted into methyl 5 - acetoxy - 4 - methylpentanoate (7), showing no apparent []_D, and 2β - acetoxy - 3β,14 - dihydroxy - 5β - pregn - 7 - ene - 6,20 - dione (8). Chemical and physiochemical studies have shown the configurations at C-20 and C-22 to be R. Inokosterone has thus been concluded to be a mixture of C-25 epimers of (20R,22R) - 2β,3β,14,20,22,26 - hexahydroxy - 5β - cholest - 7 - en - 6 - one (1). After the synthesis of the model compound, a C-25 epimeric mixture of (20R,22R) - 3β,20,22,26 - tetrahydroxy - 5 - cholestane (23), inokosterone has been synthesized via (20R) - 2β,3β,14,20 - tetrahydroxy - 20 - formyl - 5β - pregn - 7 - en - 6 - one (25) by Grignard reaction with 4 - (tetrahydrofuran - 2 - yloxy) - 3 - methylbutynylmagnesium bromide (15) followed by hydrogenation and hydrolysis. The use of an NMR shift reagent with the inokosterone acetates (9, 29) and the optical activity measurement of - methylglutaric acid (3) derived from inokosterone have established that inokosterone is a 1:2 mixture of the C-25 R and S epimers.     

Application of the intramolecular wadsworth-emmons reaction to bicyclo[3.3.0]oct - Δ - en - 3 - ones. Synthesis and x-ray structure of a novel

The cyclisation of β,ε-diketophosplionates is shown to provide an expeditious route to bicyclo[3.3.0]oct - Δ^1,2 - en - 3 - ones, which lack substitoents at C-2 and C-5. Application of the method to the parent member 12 results in the formation of a novel dimer 16 whose structure has been determined by X-ray crystallography. The dimer is thought to derive from 12 by a double Michael addition sequence involving the allyl anion 13 and the enolate 15.     

Altered selectivity of reduction of steroidal carbonyls

The reduction of steroidal ketones in different solvents yielded different products. These conditions which altered the normal path, yielded a selective reduction of the Δ⁴-3 carbonyl without the concomitant reduction of the C-17 or C-20 ketones; this permitted a one step partial synthesis of 3β-hydroxy-Δ⁴-pregnen-20-one (I), 3β-hydroxy-5-pregnan-20-one (II), and of 3β,11β-dihydroxyandrostan-17-one (IV).     

Some intramolecular rearrangements when pentofuranoses are treated with diethylaminosulphur trifluoride (DAST)

Treatment of methyl 2,3-O-isopropylidene-β- -ribofuranoside with DAST gave a goodyield of 2,3-O-isopropylidene-5-O-methyl-β- -ribofuranosyl fluoride in which the methoxygroup had migrated from C-1 → C-5 and been replaced with retention of configurationby fluorine. The corresponding aldehyde when treated under similar conditions underwenta similar migration to give 5-deoxy-5-fluoro-2,3-O-isopropylidene-5-O-methyl-β- -ribofuranosylfluoride. A similar migration occurred with methyl 2′,3′-di-O-acetyl-β- -ribofuranosideand with acetyl 2,3-O-isopropylidene - -ribofuranose but not with 1,2,3-tri-O-acetyl- -ribofuranose. Thus the migration depends upon the migratory aptitude of thesubstituent at C-1 and the conformation of the furanose ring. Two ribofuranosyl fluorideswere used as starting materials from which to make nucleosides by the method of Noyoriand Hayoshi.     

Improved access to 19-nor-7β, 8β-methylene-taxoids and formation of a 7-membered C-ring analog of doxetaxel by electrochemistry

A new route to semisynthetic 19-nor-7β, 8β-methylene taxoids, such as compound 8, from the 7-O-trifluoromethanesulfonyl derivative 6 is reported. Evidence for a dissociation of the triflate to form a carbocation at C-7 under the reaction conditions is presented. Electrochemical reduction of the cyclopropane taxoid 8 gives, besides the expected 10-dehydroxy-cyclopropane analog 10, the 7-membered C-ring derivative 11.     

Novel triterpenoid saponins from Mimusops elengi

Two novel triterpenoid saponins, mimusopin ( 3-O-β-D-glucopyranosyl-2β, 3β, 6β, 23-tetrahydroxyolean-12-en-28-oic acid 28-O--L-rhamnopyranosyl-(1→3)-β-D-xylopyranosyl-(1→4)[a-L-rhamnopyranosyl-(1→ 3)]--L-rhamnopyranosyl-(1→2)--L-arabinopyranoside)(1) and mimusopsin 3-O-[β-D-glucopyranosyl-(1→3)β-D-gluco-pyranosyl]-2β, 3β, 6β, 23-tetrahydroxyolean-12-en-28-oic acid 28-O--L-rhamnopyranosyl-(1→3)-β-D-xylopyranosyl-(1→4)--L-rhamnopyranosyl-(1→2)--L-arabinopyranoside (2) were isolated from the seeds of Mimusops elengi. Their structures were elucidated by a combination of 2D-NMR (COSY, HOHAHA, HETCOR, HMBC and NOESY), FAB-MS/MS and strategic chemical degradation. In addition, molecular mechanics and dynamics studies showed that the lack of a ¹³C glycosylation shift at the C-4 of the inner rhamnose in 1 could be correlated with distortion in the corresponding torsion angles.     

Sugar silanes: versatile reagents for stereocontrolled glycosylation via intramolecular aglycone delivery

A new method for the intramolecular glycosylation of alcohols is described. Utilizing carbohydrate-derived silanes, the catalytic dehydrogenative silylation of alcohols is followed by intramolecular glycosylation. Appropriate combinations of silane position and protecting groups allow highly selective access to β-manno, α-gluco, or β-gluco stereochemical relationships as well as 2-azido-2-deoxy-β-gluco- and 2-deoxy-β-glucosides. Intramolecular aglycone delivery from the C-2 or C-6 position provides 1,2-cis or 1,2-trans glycosides, respectively. Multifunctional acceptor substrates such as hydroxyketones and diols are tolerated and are glycosylated in a site-selective manner.     

A total synthesis of (±)-isocomene and (±) β-isocomene by an intramolecular ene reaction

The racemic sesquiterpenes isocomene 1 and β-isocomene 22 have been synthesized starting from 1,7-octadien-3-one 10 in a stereoselective manner. In the key step 12 → 13 (Scheme 5) the C-7, C-8-bond was formed by an intramolecular thermal ene reaction. Further transformations of 13 (Scheme 6) involved successively ring contraction 18 → 19, elimination 21 → 22 and olefin isomerization 22 → 1.     

Dye sensitized luminescent europium nanoparticles and its time-resolved fluorometric assay for DNA

High performance liquid chromatography (HPLC) method has been developed for simultaneous quantification of limonoid aglycones and glucosides on a reversed phase C₁₈ column using a binary solvent system, coupled with diode array detector. Seven limonoids such as limonin, nomilin, isolimonic acid, ichangin, isoobacunoic acid, limonin 17-β-d glucopyranoside and deacetyl nomilinic acid 17-β-d glucopyranoside were separated and detected at 210 nm. Furthermore, limonoids were separated, identified and quantified in four varieties of citrus fruits and seeds using developed method. Limonin and limonin glucoside were found to be the predominant limonoid aglycone and glucoside, respectively, in all tested samples. The sensitivity of the method was found to be 0.25–0.50 μg for tested limonoids.     

Starfish saponins,part 8. Structure of nodososide,a novel type of steroidal glycoside from the starfish protoreaster nodosus

A novel steroidal glycoside has been isolated from the starfish Protoreaster nodosus. The structure includes a 3β,5α,6β,8β,15α,24ξ-hexahydroxysteroidal moiety and a sugar moiety [2-0-methyl-β-D-xylopyranosyl-(1 → 2)-α-L-arabinofuranosyl] which is glycosidically attached at C-24 of the aglycone.     

Stereoselective synthesis of hyptolide and 6-epi-hyptolide

The first stereoselective syntheses of the naturally occurring, ,β-unsaturated lactone hyptolide 1 and of its nonnatural epimer at C-6 are described. Ethyl l-lactate was the chiral starting material. Key steps of these syntheses were a Brown's asymmetric allylation, a Carreira's asymmetric ethynylation and a ring closing metathesis.     

Triterpene glycosides from the roots of Codonopsis lanceolata

In the course of the development of new designer foods using the roots of Codonopsis lanceolata, we found that hot-water extracts of C. lanceolata recovered decreased testosterone levels in the blood and accelerated the restoration of reproductive dysfunction induced by hyperthermic treatment in male mice. Thus we studied the constituents of the polar fraction of the roots of C. lanceolata and identified six new triterpene saponins, lancemasides B (2), C (3), D (4), E (5), F (6), and G (7), along with the known saponin lancemasaide A (1) and phenylpropanoid glycosides 8-10. The structures of the new compounds 2-7 were determined by means of spectral data including 2D-NMR studies and chemical reactions to be oleanan-type bisdesmoside with sugars at C-3 and C-28. Compounds 2-6 have echinocystic acid as an aglycone, and compound 7 has asterogenic acid as an aglycone. Identification of the sugars and determination of their D,L-chiralities were carried out by application of the exciton chirality method to the per-O-p-bromobenzoylmethyl sugar derived from saponins.     

Structures and cytotoxic properties of cucumariosides H₂, H₃ and H₄ from the sea cucumber Eupentacta fraudatrix

New triterpene glycosides, cucumariosides H? (1), H? (2) and H? (3), have been isolated from the Far Eastern sea cucumber Eupentacta fraudatrix. The structures of 1-3 were elucidated using extensive NMR spectroscopy (1H- and 13C-NMR, DEPT, 1H-1H COSY, 1D TOCSY, H2BC, HMBC, heteronuclear single-quantum coherence, and NOESY) and ESI-MS. Glycosides 1-3 are monosulphated branched pentaosides having rare 3-O-methyl-D-xylose as a terminal monosaccharide. Glycosides 1 and 3 contain holostane aglycones, whereas 2 has a 23,24,25,26,27-pentanorlanostane aglycone with an 18(16)-lactone, which is also uncommon for the sea cucumbers. Glycoside 3 contains a very rare ethoxyl radical at C-25 of the aglycone side chain, and it is most probably an artefact that was formed during long storage of the ethanolic extract. Cytotoxic activities of 1-3 against mouse spleen lymphocytes, haemolytic activity against mouse erythrocytes and Ehrlich carcinoma cells have been studied. The presence of 25-hydroxy group in aglycone moiety significantly decreased the activities.     

Synthesis of acyclic nucleosides and other C-1 substituted alditols from carbohydrates using a tandem alkoxyl radical β-fragmentation–nucleophilic addition

The oxidative β-fragmentation of alkoxyl radicals generated from easily available carbohydrates is an efficient methodology to obtain acyclic nucleosides and other C-1 substituted alditols. In the reaction conditions an oxycarbenium ion is generated, which can be trapped by a variety of oxygen, carbon and nitrogen nucleophiles, in good yields and stereoselectivities.     

Further studies on the stereochemistry of sparteine, its isomers and derivatives : Part. I. Synthesis, structure and properties of 16,17-endo-methylene-lupaniumm perchlorate, 17-β-methyllupanine and 17-β-methylsparteine

The reduction of the product (V) obtained from the reaction of δ^16,17-dehydro- lupaninium perchlorate with diazomethane leads to 17-β-methyllupanine (III) (NaBH₄- reduction) or to 17-β-methylsparteine (X) (LiAlH₄-reduction). The structures of III and X were determined by spectroscopic methods (NMR and IR) and further proved by chemical methods. The β-methyl group at C-17 has a pronounced effect on the basicity of III and X. The basicity of in is higher than that of its parent lupanine by about 1.5 pK^*_MCSunits which can be explained by additional stabilization of the C/D boat-chair conformation in III and better solvation conditions than in lupanine. The same effect leads to a decrease of the δpK^*_MCS-value of the diamine X with reference to that of sparteine by ca. 2.6 units. The methyl group in X stabilizes the C/D boat-chair conformation and hinders the formation of an intramolecular hydrogen bond in monoprotonated X, consequently the addition of a second proton is favoured and it is assumed that the diprotonated cations of X and sparteine have different conformations. The reaction intermediate 16,17-endo-methylenelupaninium perchlorate (V) was isolated and its structure was determined.     

Cardiac glycosides from Erysimum cheiranthoides

Three new cardiac glycosides named cheiranthoside VIII (1), cheiranthoside IX (2) and cheiranthoside X (3) were isolated from the seeds of Erysimum cheiranthoides. Based on spectroscopic data, the structures of 1-3 were characterized as strophanthidin 3-O-beta-D-glucopyranosyl-(1-->4)-beta-D-antiaropyranoside, cheiranthidin 3-O-beta-D-glucopyranosyl-(1-->4)-beta-D-boiviopyranoside and cheiranthidin 3-O-alpha-L-rhamnopyranosyl-(1-->4)-beta-D-digitoxopyranoside, respectively. The aglycone moiety possessing a carboxyl group at C-10 of 2 and 3 was regarded to be determined for the first time.     

Pregnane glycosides, gymnepregosides G-Q from the roots of Gymnema alternifolium.

The structural elucidation of eleven new related polyoxypregnane glycosides, gymnepregosides G (1), H (2), I (3), J (4), K (5), L (6), M (7), N (8), O (9), P (10) and Q (11), from the roots of Gymnema alternifolium (Asclepiadaceae) was achieved by a detailed study of 1H- and 13C-NMR spectral data and chemical means. The results obtained for new compounds, 1-11, show that they are (20S)-pregn-6-ene-3 beta,5 alpha,8 beta,12 beta,14 beta,17 beta,20-heptaol 3-O-glycosides, and all the sugars at C-3 are beta(i-->4)-linked. Some of them possess benzoyl, (E)- and (Z)-cin-namoyl, and tigloyl residues as the ester linkages located at C-12 and/or C-20 of the aglycone.     

Triterpene glycosides from the stems of Akebia quinata

The stems of Akebia quinata have been analyzed for their triterpene glycoside constituents, resulting in the isolation of six new triterpene glycosides, along with 19 known ones. On the basis of extensive spectroscopic analysis, including 2D NMR data, and chemical evidence, the structures of the new compounds were deter-mined to be 3beta-[(O-beta-D-glucuronopyranosyl-(1-->3)-alpha-L-arabinopyranosyl)oxy]olean-12-en-28-oic acid O-alpha-L-rhamnopyranosyl-(1-->4)-O-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl ester, 3beta-[(O-beta-D-glucuronopyranosyl-(1-->3)-O-[alpha-L-rhamnopyranosyl-(1-->2)]-alpha-L-arabinopyranosyl)oxy]olean-12-en-28-oic acid O-alpha-L-rhamnopyranosyl-(1-->4)-O-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl ester, 3beta-[(O-beta-D-glucuronopyranosyl-(1-->3)-alpha-L-arabinopyranosyl)oxy]-23-hydroxyolean-12-en-28-oic acid O-alpha-L-rhamnopyranosyl-(1-->4)-O-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl ester, 3beta-[(O-beta-D-glucuronopyranosyl-(1-->3)-O-[alpha-L-rhamnopyranosyl-(1-->2)]-alpha-L-arabinopyranosyl)oxy]-23-hydroxyolean-12-en-28-oic acid O-alpha-L-rhamnopyranosyl-(1-->4)-O-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl ester, 3beta-[(O-beta-D-glucopyranosyl-(1-->3)-O-[alpha-L-rhamnopyranosyl-(1-->2)]-alpha-L-arabinopyranosyl)oxy]-29-hydroxyolean-12-en-28-oic acid, and 3beta-[(O-beta-D-glucopyranosyl-(1-->3)-O-[alpha-L-rhamnopyranosyl-(1-->2)]-alpha-L-arabinopyranosyl)oxy]-23,29-dihydroxyolean-12-en-28-oic acid, respectively. The main triterpene glycosides contained in the stems of A. quinata were found to have two sugar units at C-3 and C-28 of the aglycone in this study, whereas those of Akebia trifoliate were reported to possess one sugar unit at C-28 of the aglycone. It may be possible to distinguish between A. quinata and A. trifoliate chemically by comparing their triterpene glycoside constituents.     

On the origin of changes in topicity observed in Diels–Alder reactions catalyzed by Ti–TADDOLates

New C₂ symmetric TADDOLs containing different groups at the 2-position of the dioxolane ring have been prepared. The Ti catalysts derived from these have been studied in the Diels–Alder reaction of cyclopentadiene and (E)-2-butenoyl-1,3-oxazolidin-2-one. Substituents at the C-2 position of the dioxolane ring can play an important role in determining the selectivity as well as the nature of the major isomer. This effect is more important for TADDOLs containing bulky aromatic groups such as 3,5-dimethylphenyl- or 1-naphthyl at the -positions. Experimental evidence supports the hypothesis that π–π interactions between aromatic groups at the C-2 and the ones at the -positions are critical in this respect.     

Chemistry of leucomycin-X: Conformational studies on leucomycin

The conformation of leucomycin, a macrolide antibiotic with a 16-membered ring lactone, was examined in solution by IR, NMR and CD spectral analysis. The IR reveals that the five hydroxyls are all involved in intramolecular H-bonding. The NMR of the 16-membered ring lactone forming the aglycone shows that the acetyl-carbonyl at C-3, the allylic proton at C-11 and the aldehyde proton are in close proximity on the lactone ring. CD studies suggest that the conformation of the 16-membered ring lactone, especially around the lactone, is mobile and solvent dependent.