New α‐Glucosidase Inhibitors from the Mongolian Medicinal Plant Ferula mongolica

The four new and four known sesquiterpenoid derivatives 1 – 4 and 5 – 8 , respectively, were isolated from the air‐dried roots of Ferula mongolica. The structures of these compounds were determined by spectroscopic methods and found to be rel‐(2R,3R)‐2‐[(3E)‐4,8‐dimethylnona‐3,7‐dienyl]‐3,4‐dihydro‐3,8‐dihydroxy‐2‐methyl‐2H,5H‐pyrano[2,3‐b][1]benzopyran‐5‐one ( 1 ), rel‐(2R,3R)‐2‐[(3E)‐4,8‐dimethylnona‐3,7‐dienyl]‐2,3‐dihydro‐7‐hydroxy‐2,3‐dimethyl‐4H‐furo[2,3‐b][1]benzopyran‐4‐one ( 2 ), rel‐(2R,3R)‐2‐[(3E)‐4,8‐dimethylnona‐3,7‐dienyl]‐2,3‐dihydro‐7‐hydroxy‐2,3‐dimethyl‐4H‐furo[3,2‐c][1]benzopyran‐4‐one ( 3 ), rel‐(2R,3R)‐2‐[(3E)‐4,8‐dimethylnona‐3,7‐dienyl]‐2,3‐dihydro‐7‐methoxy‐2,3‐dimethyl‐4H‐furo[3,2‐c][1]benzopyran‐4‐one ( 4 ), (4E,8E)‐1‐(2‐hydroxy‐4‐methoxyphenyl)‐5,9,13‐trimethyltetradeca‐4,8,12‐trien‐1‐one ( 5 ), the rel‐(2R,3S) diastereoisomer 6 of 2 , the rel‐(2R,3S) diastereoisomer 7 of 4 , and (4E,8E)‐1‐(2,4‐dihydroxyphenyl)‐5,9,13‐trimethyltetradeca‐4,8,12‐trien‐1‐one ( 8 ). These compounds were tested as inhibitors against the enzyme α‐glucosidase. The compounds 1 – 6 and 8 exhibited significant inhibitory activity and, therefore, represent a new class of α‐glucosidase inhibitors.     

Chemical and Cytotoxic Constituents from the Stem of Machilus zuihoensis

Five new compounds, including a novel lactone, machilactone (=rel‐(2R,3aR,6E,6aS)‐2‐heptadecyl‐3a‐methyl‐6‐octadecylidene‐6,6a‐dihydrofuro[2,3‐d][1,3]dioxol‐5(3aH)‐one; 1 ), a new sesquiterpene, 3,4‐dihydroxy‐β‐bisabolol (=rel‐(1R,2S,4R)‐1‐[(1R)‐1,5‐dimethylhex‐4‐enyl]‐1‐methylcyclohexane‐1,2,4‐triol; 2 ), a new secobutyrolactone, methyl (2E)‐2‐(1‐hydroxy‐2‐oxopropyl)eicos‐2‐enoate ( 3 ), two new butyrolactones, machicolide A ( 4 ) and machicolide B ( 5 ) (=3E,4R,5R)‐ and (3Z,4R,5R)‐4,5‐dihydro‐4‐hydroxy‐5‐methoxy‐5‐methyl‐3‐octadecylidenefuran‐2(3H)‐one, resp.) as a mixture, together with known caryophyllene oxide (=4,12,12‐trimethyl‐9‐methylene‐5‐oxatricyclo[8.2.0.0^4,6]dodecane), hexacosane, tetracosanoic acid, isomahubanolide‐23 (=(3E,4R)‐4,5‐dihydro‐4‐hydroxy‐5‐methylidene‐3‐octadecylidenefuran‐2(3H)‐one), and β‐bisabolol (=(1S)‐1‐[(1S)‐1,5‐dimethylhex‐4‐enyl]‐4‐methylcyclohex‐3‐en‐1‐ol) were isolated from the stem wood of Machilus zuihoensis. The structures of these compounds were established by spectroscopic studies. The eicos‐2‐enoate ( 3 ) and β‐bisabolol exhibited marginal cytotoxicity against NUGC and HONE‐1 cancer cell lines in vitro.     

Three New Diterpenoids from Rabdosia lophanthoides var. gerardiana

Three new diterpenoids, together with three known ones, were isolated from the air‐dried whole herbs of Rabdosia lophanthoides var. gerardiana. The structures of the new diterpenoids were established as 3,4‐dihydro‐11‐hydroxy‐10‐(1‐hydroxy‐1‐methylethyl)‐2,2,6‐trimethylnaphtho[1,8‐bc]oxocin‐5(2H)‐one ( 1 ), 11,12,15‐trihydroxyabieta‐5,8,11,13‐tetraen‐7‐one ( 2 ), (2R,3S,4S,4aR,8S,9aS,13aS,16aS)‐3,4,4a,8,9,9a,10,11,12,13,14,16a‐dodecahydro‐2‐(hydroxymethyl)‐6,6,10,10‐tetramethyl‐2H‐benzo[4,5]cyclohepta[1,2‐h]pyrano[2,3‐b][1,4]benzodioxepine‐3,4,8,13a,15(6H)‐pentol ( 3 ) by spectroscopic methods, including extensive 1D‐ and 2D‐NMR analyses. The structures of the known compounds were identified by comparison of their physical and spectroscopic data with those reported in the literature.     

Synthesis and properties of new macrocyclic compounds: Utilization of bond character of hypervalent sulfur in tetraazathiapentalene derivatives

2,3‐Bis[(p‐isothiocyanatomethylphenyl)methyl]‐6,7‐dihydro‐5H‐2a‐thia(2a‐S_IV)‐2,3,4a,7a‐tetraaza‐cyclopent[cd]indene‐1,4(2H,3H)‐dithione ( 3 ), prepared by the reaction of 2,3‐dimethyl‐6,7‐dihydro‐5H‐2a‐thia(2a‐S^IV)‐2,3,4a,7a‐tetraazacyclopent‐[cd]indene‐1,4(2H,3H)‐dithione ( 1 ) with p‐xylylene diisothio‐cyanate, reacted with N,N′‐dialkyl substituted diamines to give macrocyclic compounds bearing hypervalent sulfur by a ring closure reaction in good yields. These macrocyclic compounds were converted into ring‐expanded macrocyclic compounds with release of the hypervalent sulfur by treating with NaBH₄ and CF₃COOH.     

Nonclassical Pschorr and Sandmeyer Reactions in Pyrazole Series

The diazonium salt derived from 4‐amino‐N,1,3‐trimethyl‐N‐(3‐methyl‐1‐phenyl‐1H‐pyrazol‐5‐yl)‐1H‐pyrazole‐5‐carboxamide ( 14 ) was reacted with a mixture of CuSO₄ and NaCl, with ascorbic acid as an initiator to afford the planar derivative 4,6‐dihydro‐1,4,6,8‐tetramethyl‐3‐phenyldipyrazolo[3,4‐b:4′,3′‐d]pyridin‐5(3H)‐one ( 16 ) and its unexpected isomer 4,6‐dihydro‐3,4,6,8‐tetramethyl‐1‐phenyldipyrazolo[4,3‐b:4′,3′‐d]pyridin‐5(1H)‐one ( 17 ), as well as the epimers (3S,4S)‐ (or (3S,4R)‐) and (3S,4R)‐ (or (3S,4S)‐) 4‐chloro‐2,4‐dihydro‐1′,3′,5,5′‐tetramethyl‐2‐phenylspiro[pyrazole‐3,4′(1′H)‐pyrrolo[3,4‐c]pyrazol]‐6′(5′H)‐one ( 18a and b , respectively). Epimers 18a and b were converted under basic conditions to 4′‐chloro‐N,1,3,3′‐tetramethyl‐1′‐phenyl‐[4,5′‐bi‐1H‐pyrazole]‐5‐carboxamide ( 19 ). The structures of isomers 16 and 17 determined by single‐crystal X‐ray analysis are also reported. Linear dichroism (LD) measurements for the above isomers suggest that 17 intercalates into DNA, and 17 exhibited antiproliferation activity against human NCI‐H460 pulmonary carcinoma cells.     

Non‐iterative Asymmetric Synthesis of C15 Polyketide Spiroketals

The 2,2′‐methylenebis[furan] ( 1 ) was converted to 1‐{(4R,6S))‐6‐[(2R)‐2,4‐dihydroxybutyl]‐2,2‐dimethyl‐1,3‐dioxan‐4‐yl}‐3‐[(2R,4R)‐tetrahydro‐4,6‐dihydroxy‐2H‐pyran‐2‐yl)propan‐2‐one ((+)‐ 18 ) and its (4S)‐epimer (?)‐ 19 with high stereo‐ and enantioselectivity (Schemes 1–3). Under acidic methanolysis, (+)‐ 18 yielded a single spiroketal, (3R)‐4‐{(1R,3S,4′R,5R,6′S,7R)‐3′,4′,5′,6′‐tetrahydro‐4′‐hydroxy‐7‐methoxyspiro[2,6‐dioxabicyclo[3.3.1]nonane‐3,2′‐[2H]pyran]‐6′‐yl}butane‐1,3‐diol ((?)‐ 20 ), in which both O‐atoms at the spiro center reside in equatorial positions, this being due to the tricyclic nature of (?)‐ 20 (methyl pyranoside formation). Compound (?)‐ 19 was converted similarly into the (4′S)‐epimeric tricyclic spiroketal (?)‐ 21 that also adopts a similar (3S)‐configuration and conformation. Spiroketals (?)‐ 20 , (?)‐ 21 and analog (?)‐ 23 , i.e., (1R,3S,4′R,5R,6′R)‐3′,4′,5′,6′‐tetrahydro‐6′‐[(2S)‐2‐hydroxybut‐3‐enyl]‐7‐methoxyspiro[2,6‐dioxabicyclo[3.3.1]nonane‐3,2′‐[2H]pyran]‐4′‐ol, derived from (?)‐ 20 , were assayed for their cytotoxicity toward murine P388 lymphocytic leukemia and six human cancer cell lines. Only racemic (±)‐ 21 showed evidence of cancer‐cell‐growth inhibition (P388, ED₅₀: 6.9 μg/ml).     

Four New Alkaloids from the Fermentation Broth of Armillaria mellea

Four compounds with similar structures and UV spectra were isolated from the fermentation broth of Armillaria mellea by means of preparative HPLC. Their structures were established as methyl (2S)‐1‐[2‐(furan‐2‐yl)‐2‐oxoethyl]‐5‐oxopyrrolidine‐2‐carboxylate ( 1 ), (2S)‐1‐[2‐(furan‐2‐yl)‐2‐oxoethyl]‐5‐oxopyrrolidine‐2‐carboxylic acid ( 2 ), 1‐[2‐(furan‐2‐yl)‐2‐oxoethyl]pyrrolidin‐2‐one ( 3 ) and 1‐[2‐(furan‐2‐yl)‐2‐oxoethyl]piperidin‐2‐one ( 4 ) on the basis of their 1D‐ and 2D‐NMR, and HR‐MS data. The absolute configurations of compounds 1 and 2 were determined by comparison of the experimental and calculated electronic circular dichroism (ECD) data. Additionally, four known compounds, 5 – 8 , were also isolated.     

Four novel spirooxazacamphorsultam derivatives

The chiral compounds (6aS,9S,10aR)‐11,11‐dimethyl‐5,5‐dioxo‐2,3,8,9‐tetrahydro‐6H‐6a,9‐methanooxazaolo[2,3‐i][2,1]benzisothiazol‐10(7H)‐one, C₁₂H₁₇NO₄S, (1), (7aS,10S,11aR)‐12,12‐dimethyl‐6,6‐dioxo‐3,4,9,10‐tetrahydro‐7H‐7a,10‐methano‐2H‐1,3‐oxazino[2,3‐i][2,1]benzisothiazol‐11(8H)‐one, C₁₃H₁₉NO₄S, (2), (6aS,9S,10R,10aR)‐11,11‐dimethyl‐5,5‐dioxo‐2,3,7,8,9,10‐hexahydro‐6H‐6a,9‐methanooxazolo[2,3‐i][2,1]benzisothiazol‐10‐ol, C₁₂H₁₉NO₄S, (3), and (7aS,10S,11R,11aR)‐12,12‐dimethyl‐6,6‐dioxo‐3,4,8,9,10,11‐hexahydro‐7H‐7a‐methano‐2H‐[1,3]oxazino[2,3‐i][2,1]benzisothiazol‐11‐ol, C₁₃H₂₁NO₄S, (4), consist of a camphor core with a five‐membered spirosultaoxazolidine or six‐membered spirosultaoxazine, as both their keto and hydroxy derivatives. In each structure, the molecules are linked via hydrogen bonding to the sulfonyl O atoms, forming chains in the unit‐cell b‐axis direction. The chains interconnect via weak C—H...O interactions. The keto compounds have very similar packing but represent the highest melting [507–508 K for (1)] and lowest melting [457–458 K for (2)] solids.     

Absolute configuration of strictosidinic acid

The absolute configuration of strictosidinic acid, (2S,3R,4S)‐3‐ethenyl‐2‐(β‐d ‐glucopyranosyloxy)‐4‐{[(1S)‐2,3,4,9‐tetrahydro‐1H‐pyrido[3,4‐b]indol‐1‐yl]methyl}‐3,4‐dihydro‐2H‐pyran‐5‐carboxylate, was determined from its sodium chloride trihydrate, poly[[diaqua((2S,3R,4S)‐3‐ethenyl‐2‐(β‐d ‐glucopyranosyloxy)‐4‐{[(1S)‐2,3,4,9‐tetrahydro‐1H‐pyrido[3,4‐b]indol‐2‐ium‐1‐yl]methyl}‐3,4‐dihydro‐2H‐pyran‐5‐carboxylate)sodium] chloride monohydrate], {[Na(C₂₆H₃₂N₂O₉)(H₂O)₂]Cl·H₂O}_n. The strictosidinic acid molecule participates in intermolecular hydrogen bonds of the O—H...O and O—H...Cl types. The solid‐state conformation was observed as a zwitterion, based on a charged pyridine N atom and a carboxylate group, the latter mediating the packing through coordination with the sodium cation.     

New Sesquiterpenoids from Lycianthes marlipoensis

Two new sesquiterpenoids and one derivative, lycifuranone A (= (4R)‐4,5‐dihydro‐4‐(3‐hydroxy‐2,6‐dimethylbenzyl)‐5,5‐dimethylfuran‐2(3H)‐one; 1 ), lycifuranone B (= 4,5‐dihydroxy‐3‐methyl‐2‐{[(3R)‐tetrahydro‐2,2‐dimethyl‐5‐oxofuran‐3‐yl]methyl} benzaldehyde; 2 ), and lycifuranone C (= (4R)‐4‐(3,4‐dihydroxy‐6‐{(2S,4R,6S)‐4‐[2‐(4‐hydroxy‐3‐methoxyphenyl)ethyl]‐6‐pentyl[1,3]dioxan‐2‐yl}‐2‐methylbenzyl)‐4,5‐dihydro‐5,5‐dimethylfuran‐2(3H)‐one; 3 ), respectively, have been isolated from the roots of Lycianthes marlipoensis, and their structures were established by spectroscopic methods.     

New Lignan,Benzofuran, and Sesquiterpene Derivatives from the Roots of Leontopodium alpinum and L. leontopodioides

Three new compounds, including a benzofuran, 1‐{(2R*,3S*)‐3‐(β‐D ‐glucopyranosyloxy)‐2,3‐dihydro‐2‐[1‐(hydroxymethyl)vinyl]‐1‐benzofuran‐5‐yl}ethanone ( 1 ), a lignan, [(2S,3R,4R)‐4‐(3,4‐dimethoxybenzyl)‐2‐(3,4‐dimethoxyphenyl)tetrahydrofuran‐3‐yl]methyl (2E)‐2‐methylbut‐2‐enoate ( 2 ), and a silphiperfolene‐type sesquiterpene, [(1S,2Z,3aS,5aS,6R,8aR)‐1,3a,4,5,5a,6,7,8‐octahydro‐1,3a,6‐trimethylcyclopenta[c]pentalen‐2‐yl]methyl acetate ( 3 ), together with the known coumarins obliquin ( 4 ) and its 5‐methoxy derivative 5 were isolated from the roots of Leontopodium alpinum. Another known coumarin derivative, 5‐hydroxyobliquin ( 6 ), was isolated from the roots of L. leontopodioides. The structures of these compounds were established by spectroscopic studies.     

Two stereoisomeric pentacyclic oxin­dole alkaloids from Uncaria tomentosa: uncarine C and uncarine E

The chloro­form solvate of uncarine C (pteropodine), (1′S,3R,4′aS,5′aS,10′aS)‐1,2,5′,5′a,7′,8′,10′,10′a‐octa­hydro‐1′‐methyl‐2‐oxospiro­[3H‐indole‐3,6′(4′aH)‐[1H]­pyrano­[3,4‐f]indolizine]‐4′‐carboxyl­ic acid methyl ester, C₂₁H₂₄N₂O₄·CHCl₃, has an absolute configuration with the spiro C atom in the R configuration. Its epimer at the spiro C atom, uncarine E (isopteropodine), (1′S,3S,4′aS,5′aS,10′aS)‐1,2,5′,5′a,7′,8′,10′,10′a‐octahydro‐1′‐methyl‐2‐oxospiro[3H‐indole‐3,6′(4′aH)‐[1H]pyrano[3,4‐f]indolizine]‐4′‐carboxylic acid methyl ester, C₂₁H₂₄N₂O₄, has Z′ = 3, with no solvent. Both form intermolecular hydrogen bonds involving only the ox­indole, with N?O distances in the range 2.759 (4)–2.894 (5) Å.     

Synthesis,Structure, and Conformation of 2′,3′‐Fused Oxathiane and Thiomorpholine Uridines

The syntheses of two 2′,3′‐fused bicyclic nucleoside analogues, i.e., 1‐[(4aR,5R,7R,7aS)‐hexahydro‐5‐(hydroxymethyl)‐4,4‐dioxidofuro[3,4‐b][1,4]oxathiin‐7‐yl]pyrimidine‐2,4(1H,3H)‐dione ( 1a ) and 1‐[(4aS,5R,7R,7aS)‐hexahydro‐7‐(hydroxymethyl)‐1,1‐dioxido‐2H‐furo[3,4‐b][1,4]thiazin‐5‐yl]pyrimidine‐ 2,4(1H,3H)‐dione ( 1b ), are described, the key step being an intramolecular hetero‐Michael addition. Their structures and conformations, previously solved by X‐ray crystallography, were analyzed in more detail, using 1D‐ and 2D‐NMR as well as HR‐MS analyses.     

Rationale on the Abnormal Effect of Temperature on the Enantioselectivity in the Asymmetric Borane Reduction of Ketones Catalyzed by L‐Prolinol

The effect of temperature on the enantioselectivity of the oxazaborolidine‐catalyzed asymmetric borane reduction of ketones was investigated in the presence of (5S)‐3‐oxa‐1‐aza‐2‐borabicyclo[3.3.0]octane (=(3aS)‐tetrahydro‐1H,3H‐pyrolo[1,2‐c][1,3,2]oxazaborole; 1a ) and its 2‐methoxy derivative ( 1b ) as catalysts, which were synthesized from L ‐prolinol with borane and trimethyl borate, respectively. The results indicate that the two catalysts induce a different temperature‐dependent enantioselectivity. The enantioselectivity of the B‐unsubstituted (5S)‐3‐oxa‐1‐aza‐borabicyclo[3.3.0]octane ( 1a ) increases with increasing temperature, while its B‐methoxy‐substituted derivative 1b shows the highest enantioselectivity at ca. 50°. (5S)‐3‐Oxa‐1‐aza‐2‐borabicyclo[3.3.0]octane ( 1a ) is more likely to dimerize than its 2‐methoxy derivative 1b . The conversion rates of L ‐proline to L ‐prolinol in the presence of different amounts of borane were also determined in this study.     

Solvent‐ and Temperature‐Controlled In Situ Ligand Reactions Mediated by CuII and 3′‐[(E)‐{[(1S,2S)‐2‐Aminocyclohexyl]imino}methyl]‐4′‐hydroxy‐4‐biphenylcarboxlic Acid

Three new compounds, CuL, CuL′, and Cu₂O₂L′′₂ (H₂L=3′‐[(E)‐{[(1S,2S)‐2‐aminocyclohexyl]imino}methyl]‐4′‐hydroxy‐4‐biphenylcarboxlic acid, H₂L′=3′‐[(E)‐{[(1S,2S)‐2‐aminocyclohexyl]imino}methyl]‐4′‐hydroxy‐5′‐nitro‐4‐biphenylcarboxlic acid, H₂L′′=3′‐(N,N‐dimethylamino methyl)‐4′‐hydroxy‐4‐biphenylcarboxlic acid), were selectively synthesized through a controlled in situ ligand reaction system mediated by copper(II) nitrate and H₂L. Selective nitration was achieved by using different solvent mixtures under relatively mild conditions, and an interesting and economical reductive amination system in DMF/EtOH/H₂O was also found. All crystal structures were determined by single‐crystal X‐ray diffraction analysis. Both CuL and CuL′ display chiral 1D chain structures, whereas Cu₂O₂L′′₂ possesses a structure with 13×16 Å channels and a free volume of 41.4 %. The possible mechanisms involved in this in situ ligand‐controlled reaction system are discussed in detail.     

A chalcone showing positional disorder,two related diarylcyclohexenones showing enantiomeric disorder and a related hydroxyterphenyl,all derived from simple carbonyl precursors

Four compounds are reported, all of which lie along a versatile reaction pathway which leads from simple carbonyl compounds to terphenyls. (2E)‐1‐(2,4‐Dichlorophenyl)‐3‐ [4‐(prop‐1‐en‐2‐yl)phenyl]prop‐2‐en‐1‐one, C₁₈H₁₄Cl₂O, (I), prepared from 4‐(prop‐1‐en‐2‐yl)benzaldehyde and 2,4‐dichloroacetophenone, exhibits disorder over two sets of atomic sites having occupancies of 0.664 (6) and 0.336 (6). The related chalcone (2E)‐3‐(4‐chlorophenyl)‐1‐(4‐fluorophenyl)prop‐2‐en‐1‐one reacts with acetone to produce (5RS)‐3‐(4‐chlorophenyl)‐5‐[4‐(propan‐2‐yl)phenyl]cyclohex‐2‐en‐1‐one, C₂₁H₂₁ClO, (II), which exhibits enantiomeric disorder with occupancies at the reference site of 0.662 (4) and 0.338 (4) for the (5R) and (5S) forms; the same chalcone reacts with methyl 3‐oxobutanoate to give methyl (1RS,6SR)‐4‐(4‐chlorophenyl)‐6‐[4‐(propan‐2‐yl)phenyl]‐2‐oxocyclohex‐3‐ene‐1‐carboxylate, C₂₃H₂₃ClO₃, (III), where the reference site contains both (1R,6S) and (1S,6R) forms with occupancies of 0.923 (3) and 0.077 (3), respectively. Oxidation, using 2,3‐dichloro‐5,6‐dicyano‐1,4‐benzoquinone, of ethyl (1RS,6SR)‐6‐(4‐bromophenyl)‐4‐(4‐fluorophenyl)‐2‐oxocyclohex‐3‐ene‐1‐carboxylate, prepared in a similar manner to (II) and (III), produces ethyl 4′′‐bromo‐4‐fluoro‐5′‐hydroxy‐1,1′:3′,1′′‐terphenyl‐4′‐carboxylate, C₂₁H₁₆BrFO₃, (IV), which crystallizes with Z′ = 2 in the space group P. There are no significant intermolecular interactions in the structures of compounds (I) and (II), but for the major disorder component of compound (III), the molecules are linked into sheets by a combination of C—H...O and C—H...π(arene) hydrogen bonds. The two independent molecules of compound (IV) form two different centrosymmetric dimers, one built from inversion‐related pairs of C—H...O hydrogen bonds and the other from inversion‐related pairs of C—H...π(arene) hydrogen bonds. Comparisons are made with related compounds.     

Two androsterone derivatives as inhibitors of androgen biosynthesis

The title compounds, (3R,5S,5′R,8R,9S,10S,13S,14S)‐10,13‐dimethyl‐5′‐(2‐methylpropyl)tetradecahydro‐6′H‐spiro[cyclopenta[a]phenanthrene‐3,2′‐[1,4]oxazinane]‐6′,17(2H)‐dione, C₂₆H₄₁NO₃, (I), and methyl (2R)‐2‐[(3R,5S,8R,9S,10S,13S,14S)‐10,13‐dimethyl‐2′,17‐dioxohexadecahydro‐3′H‐spiro[cyclopenta[a]phenanthrene‐3,5′‐[1,3]oxazolidin‐3′‐yl]]‐4‐methylpentanoate, C₂₈H₄₃NO₅, (II), possess the typical steroid shape (A–D rings), but they differ in their extra E ring. The azalactone E ring in (I) shows a half‐chair conformation, while the carbamate E ring of (II) is planar. The orientation of the E‐ring substituent is clearly established and allows a rationalization of the biological results obtained with such androsterone derivatives.     

The diastereoisomers methyl 5‐(S)‐[2‐(R)/(S)‐methoxycarbonyl)‐2,3,4,5‐tetrahydropyrrol‐1‐ylcarbonyl]‐1‐(4‐methylphenyl)‐4,5‐dihydropyrazole‐3‐carboxylate

The title diastereoisomers, methyl 5‐(S)‐[2‐(S)‐methoxy­carbonyl)‐2,3,4,5‐tetra­hydro­pyrrol‐1‐yl­carbonyl]‐1‐(4‐methyl­phenyl)‐4,5‐di­hydro­pyrazole‐3‐carboxyl­ate and methyl 5‐(S)‐[2‐(R)‐methoxycarbonyl)‐2,3,4,5‐tetrahydropyrrol‐1‐ylcarbonyl]‐1‐(4‐methyl­phenyl)‐4,5‐di­hydro­pyrazole‐3‐carboxylate, both C₁₉H₂₃N₃O₅, have been studied in two crystalline forms. The first form, methyl 5‐(S)‐[2‐(S)‐methoxy­carbonyl)‐2,3,4,5‐tetrahydropyrrol‐1‐ylcarbonyl]‐1‐(4‐methylphenyl)‐4,5‐di­hydro­pyrazole‐3‐carboxyl­ate–methyl 5‐(S)‐[2‐(R)‐methoxy­carbonyl)‐2,3,4,5‐tetra­hydro­pyrrol‐1‐yl­carbonyl]‐1‐(4‐methylphenyl)‐4,5‐dihydropyrazole‐3‐carboxylate (1/1), 2(S),5(S)‐C₁₉H₂₃N₃O₅·2(R),5(S)‐C₁₉H₂₃N₃O₅, contains both S,S and S,R isomers, while the second, methyl 5‐(S)‐[2‐(S)‐methoxycarbonyl)‐2,3,4,5‐tetrahydro­pyrrol‐1‐ylcarbonyl]‐1‐(4‐methyl­phenyl)‐4,5‐di­hydro­pyrazole‐3‐carboxyl­ate, 2(S),5(S)‐C₁₉H₂₃N₃O₅, is the pure S,S isomer. The S,S isomers in the two structures show very similar geometries, the maximum difference being about 15° on one torsion angle. The differences between the S,S and S,R isomers, apart from those due to the inversion of one chiral centre, are more remarkable, and are partially due to a possible rotational disorder of the 2‐­(methoxycarbonyl)tetrahydropyrrole group.     

Retroracemization using new forms of Belokon's original ligand: ­intermediate NiII complexes of N‐({2‐[N‐(S)‐alkylprolylamino]phenyl}phenylmethylene)‐(S)‐phenylalanine (alkyl is 2‐picolyl, 3‐picolyl or ethyl)

In the title compounds, [N‐(phenyl{2‐[N‐(S)‐(2‐picolyl)­prolyl­amino]­phenyl}methyl­ene)‐(S)‐phenyl­alaninato]­nickel(II), [Ni(C₃₃H₃₀N₄O₃)], (I), [N‐(phenyl{2‐[N‐(S)‐(3‐picolyl)­prolyl­amino]­phenyl}methyl­ene)‐(S)‐phenyl­alaninato]­nickel(II) hemihydrate, [Ni(C₃₃H₃₀N₄O₃)]·0.5H₂O, (II), and [N‐({2‐[N‐(S)‐ethyl­prolyl­amino]­phenyl}phenyl­methyl­ene)‐(S)‐phenyl­ala­nin­ato]­nickel(II), [Ni(C₂₉H₂₉N₃O₃)], (III), the Ni^II centres have approximate square‐planar coordination geometries from N₃O donor sets. The picolyl N atoms in (I) and (II) are too remote from the metal centres to interact significantly, but the metal coordination geometries experience tetrahedral distortion and/or displacement of the metal centre from the N₃O plane. These are linked to conformational differences between the ligands of the symmetry‐independent complexes (Z′ = 2), which in turn are related to molecular packing. In (III), where a less sterically demanding ethyl group replaces the picolyl substituents, there are none of the distortions or displacements seen in (I) and (II).     

Cerebrosides from the Rhizomes of Gynura Japonica

Four new cerebrosides, gynuramides I?IV ( 1 ‐ 4 ), together with 37 known compounds were isolated from the rhizome of Gynura japonica. The structures of cerebrosides 1 ‐ 4 were determined by chemical and spectroscopic examination to be: (2S,3S,4R,8E)‐2‐[(R)‐2‐hydroxypentacosanoylamino]‐8‐en‐1,3,4‐octadecanetriol, (2S,3S,4R,8E)‐2‐[(R)‐2‐hydroxytetracosanoylamino]‐8‐en‐1,3,4‐octadecanetriol, (2S,3S,4R,8E)‐2‐[(R)‐2‐hydroxytricosanoylamino]‐8‐en‐1,3,4‐octadecanetriol, and (2S,3S,4R,8E)‐2‐[(R)‐2‐hydroxydocosanoylamino]‐8‐en‐1,3,4‐octadecanetriol.