Six new withanolide-type steroids from the leaves of Solanum cilistum

Six new withanolide-type steroids, designated cilistols v, t, i, j, y and w (1-6, respectively), were obtained from the leaves of Solanum cilistum. Their respective structures were characterized by spectroscopic means as follows: Cilistol v (1) was (22R,24Z)-1alpha,3beta,22,26-tetrahydroxyergost-5,24-diene 26-O-beta-D-glucopyranoside, which is regarded as the precursor of other withanolide-type steroids included in this title plant. Cilistol t (2) was (22R,24S,25R,26S)-24,25;22,26-diepoxy-1alpha,3beta,26-trihydroxyergost-5-ene 26-O-beta-D-glucopyranoside, and cilistols j (3) and i (4) corresponded to the substances probably formed by the cleavage of the epoxy ring at C-24 and 25 of 2. Cilistol y (5) was 3-O-sulphonyl (22R,24S,25R,26R)-1-oxo-24,25; 22,26-diepoxy-3beta,17alpha,26-trihydroxyergost-5-ene 26-O-beta-D-glucopyranoside, and cilistol w (6) corresponded to the substance obtained by the fission of the epoxy ring at C-24 and 25 of 5. The occurrence of these withanolide type steroids from Solanum genera is rare and worthy of note.     

Synthesis of the aglycone of the shark repellent pavoninin-4 using remote functionalization

[reaction: see text] The aglycone of shark repellent pavoninin-4, (25R)-5alpha-cholestan-3alpha,15alpha,26-triol 26-acetate 1a, was synthesized from (25R)-cholest-5-en-3beta,26-diol 4 (26-hydroxycholesterol) in eight steps in 18% overall yield. Breslow's remote functionalization strategy was used as a key step to introduce the C-15alpha alcohol on a steroid D ring. An efficient synthesis of the 26-hydroxycholesterol from the 16beta hydroxyl steroid, (25R)-cholest-5-ene-3beta,16beta,26-triol (3a), is also reported.     

Four novel withanolide-type steroids from the leaves of Solanum cilistum.

Four novel withanolide-type steroids named cilistols p, pm, p1 and u (1-4, respectively), were isolated from the leaves of Solanum cilistum. The respective structures were characterized by spectroscopic means as follows: cilistol p (1) was (22R,24R,25R,26S)-1-oxo-22,26-epoxy-3alpha,5alpha-cycloergostane-6beta,17alpha, 24,25,26-pentaol 26-O-beta-D-glucopyranoside, cilistol pm (2) corresponded to the 6-O-methyl ether derivative of 1; cilistol p1 (3) was represented as the 24-O-methyl ether of 1, and cilistol u (4) was shown to be the epoxide between C-24 and -25, presumably bearing cilistols p, pm and p1 by ring-opening.     

Total synthesis of plakortide E and biomimetic synthesis of plakortone B

The total synthesis of plakortide E (1a) is reported. A novel palladium-catalyzed approach towards 1,2-dioxolanes as well as an alternative substrate-controlled route leading exclusively to cis-highly substituted 1,2-dioxolanes have been developed. A lipase-catalyzed kinetic resolution was employed to provide optically pure 1,2-dioxolane central cores. Coupling of the central cores and side chains was achieved by a modified Negishi reaction. All four isomeric structures of plakortide E methyl ester, namely, 26a-d were synthesized. One of the structures, 26d, was shown to be identical with the natural plakortide E methyl ester on the basis of (1)H, (13)C NMR spectra and specific rotation comparisons. With the plakortide E methyl ester (4S,6R,10R)-(-)-cis-26d and its other three isomers in hand, we successfully converted them into (3S,4S,6R,10R)-plakortone B (2a), and its isomers ent-2a, 2b and ent-2b via an intramolecular oxa-Michael addition/lactonization cascade reaction. Finally, saponification converted 1,2-dioxolane 26d into plakortide E (1a) whose absolute configuration (4S,6R,10R) was confirmed by comparison of spectral and physical data with those reported.     

New furostanol saponins from Allium ascalonicum L

An analysis of the polar extracts from Allium ascalonicum L. led to the isolation of two new furostanol saponins (compound 1 and 2) and two known furostanol saponins (compound 3 and 4). On the basis of 1D and 2D NMR (including (1)H, (13)C NMR, (1)H--(1)H COSY, HSQC, TOCSY, HMBC, and NOESY), FAB-MS spectrometry, and chemical methods, their structures were elucidated as (25R)-26-O-beta-D-glucopyranosyl-22-hydroxy-5alpha-furost-2-one-3beta, 5, 6beta, 26-tetraol-3-O-alpha-L-rhamnopyranosyl-(1-->2)-beta-D-glucopyranoside (ascalonicoside C, 1), (25R)-26-O-beta-D-glucopyranosyl-22-methoxy-5alpha-furost-2-one-3beta, 5, 6beta, 26-tetraol- 3-O-alpha-L-rhamnopyranosyl-(1-->2)-beta-D-glucopyranoside (ascalonicoside D, 2), (25R)-26-O-beta-D-glucopyranosyl-22-hydroxy-5-ene-furostan-3beta, 26-diol-3-O-alpha-L-rhamnopyranosyl-(1-->4)-alpha-L-rhamnopyranosyl-(1-->4)-[alpha-L-rhamnopyranosyl-(1-->2)]-beta-D-glucopyranoside (dichotomin, 3), and (25R)-26-O-beta-D-glucopyranosyl-22-hydroxy-5-ene-furostan-3beta, 26-diol-3-O-alpha-L-rhamnopyranosyl-(1-->2)-[alpha-L-arabinofuranosyl-(1-->4)]-beta-D- glucopyranoside (parisaponin I, 4).     

Medicinal foodstuffs. XVII. Fenugreek seed. (3): structures of new furostanol-type steroid saponins, trigoneosides Xa, Xb, XIb, XIIa, XIIb, and XIIIa, from the seeds of Egyptian Trigonellafoenum-graecum L

Six new furostanol-type steroid saponins called trigoneosides Xa, Xb, XIb, XIIa, XIIb, and XIIIa were isolated from the seeds of Egyptian Trigonella foenum-graecum L. (Leguminosae) together with six known furostanol-type steroid saponins: trigoneosides Ia, Ib, and Va, glycoside D, trigonelloside C, and compound C. The structures of trigoneosides Xa, Xb, Xlb, XIIa, Xllb, and XIIIa were determined on the basis of chemical and physicochemical evidence as 26-O-beta-D-glucopyranosyl-(25S)-5alpha-furostane-2alpha+ ++,3beta,22xi,26-tetraol 3-O-alpha-L-rhamnopyranosyl(1-->2)-,beta-D-glucopyranoside, 26-O-beta-D-glucopyranosyl-(25R)-5alpha-furostane-2 alpha,beta,22xi,26tetraol 3-O-alpha-L-rhamnopyranosyl(l -->2)-beta-D-glucopyranoside, 26-O-beta-D-glucopyranosyl-(25R)-5alpha-furostane2alpha++ +,beta,22xi,26-tetraol 3-O-beta-D-xylopyranosyl(l -->4)-beta-D-glucopyranoside, 26-O-beta-D-glucopyranosyl-(25S)-furost-4-ene-3beta,22xi,26- triol 3-O-Ca-L-rhamnopyranosyl(1-->2)-beta-D-glucopyranoside, 26-O-beta-D-glucopyranosyl-(25R)-furost-4-ene-3beta,22xi+ ++,26-triol 3-O-alpha-L-rhamnopyranosyl(1-->2)-beta-D-glucopyranoside, and 26-O-beta-D-glucopyranosyl(25S)-furost-5-ene-3beta,22xi,26-t riol 3-O-alpha-L-rhamnopyranosyl(1-->2)-beta-D-glucopyranosyl (1-->3)-beta-D-glucopyranosyl(1--4)]-beta-D-glucopyranoside, respectively.     

Structures of two new steroidal glycosides, soladulcosides A and B from Solanum dulcamara

The structures of two new steroidal glycosides named soladulcosides A and B, isolated from the aerial parts of Solanum dulcamara including new sapogenols, were elucidated as (22R, 25R)-3 beta, 15 alpha, 23 alpha-trihydroxy-5 alpha-spirostan-26-one 3-O-alpha-L-rhamnopyranosyl-(1----2)-beta-D-glucopyranoside and (22R, 25R)-3 beta,23 alpha-dihydroxy-5 alpha-spirostan-26-one 3-O-alpha-L-rhamnopyranosyl-(1----2)-[alpha-L-rhamnopyranosyl-(1----4)]- beta-D-glucopyranoside, respectively.     

Two New Steroidal Saponins from Tacca plantaginea

Two new C27 steroidal glycosides, named taccaoside A(1) and B(2), were isolated from the traditional Chinese herb Tacca plantaginea. The spectroscopic and chemical evidences revealed their structures to be 26-O-β-D-glucopyranosyl-(25R)-3β,26-dihydroxy furost-5,20-diene-3-O-[α-L-rhamnopyranosyl(1→2)]-[α-L-rhamnopyranosyl(1→3)]-β-D-glucopyranoside(1) and 26-O-β-D-glucopyranosyl-(25R)-3β,26-dihydroxy furost-5,20-diene-3-O-[α-L-rhamnopyranosyl-(1→2)]-[β-D-glucopyranosyl(1→3)-α-L-rhamnopyranosyl(1→3)]-β-D-glucopyranoside(2),respectively.     

Absolute stereochemistry of ulapualide A

[structure: see text] The structure of ulapualide A (1) has been solved by X-ray crystallography in a complex with G-actin. The stereochemical configuration was assigned as 3S,9S,22S,23R,24S,26S,27S,31R,32R,33R.     

Synthesis of the C(21)-C(26) fragment of superstolide A: concerning the stereochemistry of (E)-crotylboration reactions of alaninal derivatives

A stereoselective synthesis of the C(21)-C(26) fragment of superstolide A has been completed. The absolute and relative stereochemistry of intermediate 14 has been conclusively proven by NMR and X-ray diffraction methods. In the course of this work, it was found that the stereochemistry of 3 had been misassigned in our previously reported synthesis of the C(18)-C(26) segment. This error stems from the unexpected diastereoselectivity in the double asymmetric reaction of N-acetyl-d-alaninal 1 and the tartrate ester modified (E)-crotylboronate (R,R)-2.     

Synthesis of chiral pyrrolo[1,2-c]thiazoles via intramolecular dipolar cycloaddition of münchnones: an interesting rearrangement to pyrrolo[1,2-c]thiazines

Intramolecular dipolar cycloaddition of bicyclic münchnones, 5H,7H-thiazolo[3,4-c]oxazol-4-ium-1-olates, derived from cyclodehydration of 2-substituted-N-acylthiazolidine-4-carboxylic acids are reported. A range of new pyrrolo[1,2-c]thiazole derivatives (7, 14, 15, 20, 23, and 26) were obtained as single enantiomers from 2-phenylthiazolidines, 2-benzoylthiazolidines, and 2-methylthiazolidine-4-carboxylates. Pyrrolo[1,2-c][1,4]thiazine derivative 27 was also obtained from pyrrolo[1,2-c]thiazole derivative 26. The structures of methyl (2R,4R)-2-(p-methoxybenzoyl)thiazolidine-4-carboxylate (17a), methyl (2R,4R)-2-(p-methoxybenzoyl)-N-(prop-2-ynyloxyacetyl)thiazolidine- 4-carboxylate (18), and 3-oxo-4-phenyl-3,4,6,8-tetrahydro-1H-furo[3',4':2,3]pyrrolo[1,2-c][1,4]thiazine (27) were determined by X-ray crystallography. Chirooptical studies of the pyrrolo[1,2-c]thiazoles were done by confirming the absolute configuration at the chiral center C-3.     

Studies on the constituents of solanaceous plants. (46). Steroidal glycosides from the fruits of Solanum anguivi

Three new glycosides named anguiviosides A-C were isolated from the fruits of Solanum anguivi and characterized as follows:3-O-beta-chacotrioside (1), 3-O-[4-O-maloyl-alpha-L-rhamnopyranosyl(1-->2)]-alpha-L-rhamnopyra nosyl(1-->4)-beta-D-glucopyranoside (2) and 3-O-alpha-L-rhamnopyranosyl(1-->2)-beta-D-xylopyranosyl(1-->3)]-beta-D-+ ++glucopyranoide (3), of (25R,26R)-spirost-5-en-3beta,26-diol.     

Synthesis of [4,5-Bis(hydroxymethyl)-1,3-dithiolan-2-yl]nucleosides as Potential Inhibitors of HIV(1)

The synthesis of [4,5-bis(hydroxymethyl)-1,3-dithiolan-2-yl]nucleosides is described. (2S,3S)-1,2:3,4-Diepoxybutane (13) was reacted with potassium thiocyanate to give (2R,3R)-1,2:3,4-diepithiobutane (14). Thiiranering opening with acetate followed by deacetylation gave (2R,3R)-2,3-dithiothreitol (19) which was silylated and treated with trimethyl orthoformate to give the 2-methoxy-1,3-dithiolane 20. Condensation of 20 with silylated thymine, uracil, N(4)-benzoylcytosine and 6-chloropurine using a modified Vorbrüggen procedure, followed by deprotection, gave the nucleoside analogues. Compounds 26, 28, and 30 were found to be inactive when tested for anti-HIV activity in vitro.     

Alpha-hydroxylation at C-15 and C-16 in cholesterol: synthesis of (25R)-5alpha-cholesta-3beta,15alpha,26-triol and (25R)-5alpha-cholesta-3beta,16alpha,26-triol from diosgenin

[reaction: see text] (25R)-5alpha-cholesta-3beta,16alpha,26-triol 7b and (25R)-5alpha-cholesta-3beta,15alpha,26-triol 10b were synthesized, via (25R)-5alpha-cholesta-3beta,16beta,26-triol 5a, from diosgenin 3 in 52% yield over six steps and 47% yield over eight steps, respectively. An efficient method for inversion of a C-16beta hydroxyl to the C-16alpha position and a short method for transposition of a C-16beta hydroxyl to the C-15alpha position via the unexpected beta-reduction of a C-15 ketone in a steroid are reported.     

A New Furostanol Glycoside from Polygonatum odoratum

A new furostanol component glycosylated only at C-26 was isolated from the rhizomes of Polygonatum odoratum(Mill.)Druce,and its structure was characterized as 22-hydroxy-25(R and S)furost-5-en-12-on-3β,22,26-triol 26-O-β-D-glucopyranoside on the basis of spectroscopic techniques and chemical methods.     

Four new 3,5-cyclosteroidal saponins from Dracaena surculosa

Further search for steroidal compounds contained in Dracaena surculosa (Agavaceae) led to the isolation of two new 3,5-cyclospirostanol saponins (1, 2) and two new 3,5-cyclofurostanol saponins (3, 4). Their structural assignment was established by spectroscopic analysis and a few chemical transformations as (24S,25R)-1beta-[(beta-D-fucopyranosyl)oxy]-6beta-hydroxy-3alpha,5alpha-cyclospirostan-24-yl beta-D-glucopyranoside (1), (24S,25R)-1beta-[(beta-D-glucopyranosyl)oxy]-6beta-hydroxy-3alpha,5alpha-cyclospirostan-24-yl beta-D-glucopyranoside (2), (25S)-1beta-[(beta-D-glucopyranosyl)oxy]-6beta-hydroxy-22alpha-methoxy-3alpha,5alpha-cyclofurostan-26-yl beta-D-glucopyranoside (3), and (25S)-1beta-[(beta-D-fucopyranosyl)oxy]-6beta-hydroxy-22alpha-methoxy-3alpha,5alpha-cyclofurostan-26-yl beta-D-glucopyranoside (4), respectively.     

Steroid glycosides of the seeds ofPetunia hybrida II. The structures of petuniosides I,L, and N

Three new steroid glycosides of the furostan series, petuniosides L L, and N, have been isolated from the seeds of Petunia hybrida L. Petunioside 1is (25 R)-5ot~-furostan-3ß, 22ot~, 26-triol 3-O-ß-D-galactopyranoside 26-O-ß-D-glucopyranoside, petunioside L. (25R)-5ot-furostan-3ß,22ot~,6-triol 3-O-[O-ß-D-glucopyranosyl-(1--,4)-ß-D-galactopyranoside] 26-O-ß-D-glucopyranoside, andpetunioside N is (25R)-5ot~-furostan-3ß,22ot,26-triol 3-0-[0-ß-D-glucopyranosyl- (1 --,2)-O-ß-D-glucopyranosyl- (1 --,4)-ß-D-galactopyranoside] 26-O-ß-D-glucopyranoside.Institute of Genetics, Academy of Sciences of the Republic of Moldova, 277002, Kishinev, ul. Desnaya, 20. Translated from Khimiya Prirodnykh Soedinenii, No. 2, pp. 247–252, March-April, 1995. Original article submitted August 29, 1994.     

The first enantiomerically pure [n]triangulanes and analogues: sigma-[n]helicenes with remarkable features

(M)-(-)- and (P)-(+)-Trispiro[2.0.0.2.1.1]nonanes [(M)- and (P)-3] as well as (M)-(-)- and (P)-(+)-tetraspiro[2.0.0.0.2.1.1.1]undecanes [(M)- and (P)-4]-enantiomerically pure unbranched [4]- and [5]triangulanes-have been prepared starting from racemic bicyclopropylidenecarboxylic [(1RS)-12] and exo-dispiro[2.0.2.1]heptane-1-carboxylic [(1RS,3SR)-13] acids. The optical resolutions of rac-12 and rac-13 furnished enantiomerically pure acids (S)-(+)-12, (R)-(-)-12, (1R,3S)-(-)-13, and (1S,3R)-(+)-13. The ethyl ester (R)-25 of the acid (R)-(-)-12 was cyclopropanated to give carboxylates (1R,3R)-26 and (1R,3S)-26. The ester (1R,3S)-26 and acids (1R,3S)-13 and (1S,3R)-13 were converted into enantiomerically pure methylene[3]triangulanes (S)-(-)- and (R)-(+)-28. An alternative approach consisted of an enzymatic deracemization of endo-[(1SR,3SR)-dispiro[2.0.2.1]heptyl]methanol (rac-20) or anti-[(1SR,3RS)-4-methylenespiropentyl]methanol (rac-18). This afforded (S)-(-)- and (R)-(+)-28 (starting from rac-20), as well as enantiomerically pure (M)-(-)- and (P)-(+)-1,4-dimethylenespiropentanes [(M)- and (P)-23] starting from rac-18. The methylenetriangulanes (S)-(-)- and (R)-(+)-28 were cyclopropanated furnishing (M)- and (P)-3. The rhodium-catalyzed cycloaddition of ethyl diazoacetate onto (S)-(-)- and (R)-(+)-28 yielded four diastereomeric ethyl trispiro[2.0.0.2.1.1]nonane-1-carboxylates in approximately equal proportions. The enantiomerically pure esters (1R,3S,4S)- and (1S,3R,4R)-30 were isolated by careful distillation and then transformed into [5]triangulanes (M)- and (P)-4 using the same sequence of reactions as applied for (M)- and (P)-3. The structures of the key intermediates (R)-12 and rac-31 were confirmed by X-ray analyses. Although [4]- and [5]triangulanes have no chromophore which would lead to any significant absorption above 200 nm, they have remarkably high specific rotations even at 589 nm with [alpha](20)D=-192.7 [(M)-3, c=1.18, CHCl(3))] or +373.0 [(P)-4, c=1.18, CHCl(3))]. This remarkable optical rotatation is in line with their helical arrangement of sigma bonds, as confirmed by a full valence space single excitation configuration interaction treatment (SCI) in conjunction with DFT computations at the B3LYP/TZVP//B3LYP/6-31+G(d,p) level of theory which reproduce the ORD very well. Thus, it is appropriate to call the helically shaped unbranched [n]triangulanes the "sigma-[n]helicenes", representing the sigma-bond analogues of the aromatic [n]helicenes.     

The Asymmetric Syntheses of Methyl <small>D</small>-Digitoxoside, <small>L</small>-Oleandrose and <small>L</small>-Cymarose from Methyl Sorbate, an Achiral Precursor

The addition of 4?eq of chloral to osmundalactone (4S,5R)-4 gave quantitative formation of the hemiacetal derivative (4S,5R)-8, which was treated with methane sulfonic acid to afford the intramolecular Micheal addition product (+)-(3S,4S,5R)-9 possessing a 3,4-cis-dihydroxy-δ-lactone in 78% overall yield from (4S,5R)-4. The obtained (+)-(3S,4S,5R)-9 was subsequently converted to methyl D-digitoxoside (pyranoside) (12) in 13% overall yield and methyl D-digitoxoside (furanoside) (12) in 20% overall yield. The reaction of benzyl-osmundalactone (4R,5S)-3 and MeOH in the presence of Amberlyst A-26 as a basic catalyst gave 3,4-trans-δ-lactone (－)-(3S,4R,5S)-20 in 28% yield and 3,4-cis-δ-lactone (－)-(3R,4R,5S)-21 in 45% yield. Dibal-H reduction of (－)-(3S,4R,5S)-20 followed by catalytic hydrogenation gave L-oleandrose (6) in 86% overall yield, while Dibal-H reduction of (－)-(3R,4R,5S)-21 followed by catalytic hydrogenation provided L-cymarose (7) in 85% overall yield.     

Complete (1)H and (13)C assignments of the four major saponins from Dioscorea villosa (wild yam)

Complete (1)H and (13)C spectral assignments for the four major steroidal saponins isolated by methanolic extraction of the roots of Dioscorea villosa, collected in North Carolina, United States (in summer and autumn), are presented in this paper. The structures were determined by a combination of (1)H, (13)C and 2D NMR techniques and were found to be ((3beta,25R)-26-(beta-D-glucopyranosyloxy)-22-methoxyfurost-5-en-3-yl-O-beta-D-glucopyranosyl-(1 --> 3)-O-beta-D-glucopyranosyl-(1 --> 4)-O-[alpha-L-rhamnopyranosyl-(1 --> 2)]-beta-D-glucopyranoside (1) (or methyl parvifloside), ((3beta,25R)-26-(beta-D-glucopyranosyloxy)-22 methoxyfurost-5-en-3-yl-O-alpha-L-rhamnopyranosyl-(1 --> 2)-O-[beta-D-gluco- pyranosyl-(1 --> 4)]-beta-D-glucopyranoside (2) (or methyl protodeltonin), (3beta,25R)-spirost-5-en-3-yl-O-beta-D-glucopy ranosyl-(1 --> 3)-O-beta-D-glucopyranosyl-(1 --> 4)-O-[alpha-L-rhamnopyranosyl-(1 --> 2)]-beta-D-glucopyranoside (3) (or Zingiberensis saponin I) and (3beta,25R)-spirost-5-en-3-yl-O-alpha-L-rhamnopyranosyl-(1 --> 2)-O-[beta-Ds-glucopyranosyl -(1 --> 4)]-beta-D-glucopyranoside (4) (or deltonin).