Two key chiral intermediates in a new 4‐hydroxy­isoleucine synthesis

We present the crystal and molecular structure of two key compounds of a new synthesis strategy for isomers of natural (2S,3R,4S)‐4‐hydroxyisoleucines, 2,3,5,6,7,8‐hexa­hydro‐3‐(1‐hydroxy‐1‐methyl‐2‐oxo­propyl)‐6,8‐methano‐7,7,8a‐tri­meth­yl‐5H‐1,4‐benzoxazin‐2‐one, C₁₆H₂₃NO₄, and 2,3,5,6,7,8‐hexa­hydro‐3‐(1‐methyl‐2‐oxo­propyl)‐6,8‐methano‐7,7,8a‐tri­meth­yl‐5H‐1,4‐benzoxazin‐2‐one, C₁₆H₂₃NO₃. A new optically pure chiral oxazinone auxiliary derived from (1R,2R,5R)‐2‐hydroxy­pinan‐3‐one was used.     

A pair of epimeric 13‐hydroxy‐2,3,6,7‐tetra­methoxy‐8b,11,12,12a,13,13a‐hexa­hydro‐9H‐9a‐aza­cyclo­penta­[b]tri­phenyl­ene‐10‐ones

The structures of two compounds which are intermediates in the synthesis of phenanthroindolizidine alkaloids have been determined. (8bS,13aS,14R,14aR)‐8b,9,11,12,13,13a,14,14a‐Octa­hydro‐14‐hydroxy‐2,3,6,7‐tetra­methoxy­dibenzo­[f,h]pyrrolo[1,2‐b]­isoquinolin‐11‐one acetone solvate, C₂₄H₂₇NO₆·C₃H₆O, (II), crystallizes in a chiral space group with one solvent mol­ecule (acetone) present in the asymmetric unit. On the other hand, (8bS,13aS,14S,14aR)‐8b,9,11,12,13,13a,14,14a‐octa­hydro‐14‐hydroxy‐2,3,6,7‐tetra­methoxy­dibenzo­[f,h]pyrrolo[1,2‐b]­isoquinolin‐11‐one, C₂₄H₂₇NO₆, (III), crystallizes in a centrosymmetric space group with two mol­ecules in the asymmetric unit and with no solvent present. The two mol­ecules in the asymmetric unit of (III) are structurally the same. Compounds (II) and (III) are epimers at the C atom carrying the OH group; otherwise they are very similar in structure.     

Three ginkgolide hydrates from Ginkgo biloba L.: ginkgolide A monohydrate,ginkgolide C sesquihydrate and ginkgolide J dihydrate,all determined at 120 K

A low‐temperature structure of ginkgolide A monohydrate, (1R,3S,3aS,4R,6aR,7aR,7bR,8S,10aS,11aS)‐3‐(1,1‐dimethylethyl)‐hexa­hydro‐4,7b‐di­hydroxy‐8‐methyl‐9H‐1,7a‐epoxymethano‐1H,6aH‐cyclo­penta­[c]­furo­[2,3‐b]­furo­[3′,2′:3,4]­cyclopenta­[1,2‐d]­furan‐5,9,12(4H)‐trione monohydrate, C₂₀H₂₄O₉·H₂O, obtained from Mo Kα data, is a factor of three more precise than the previous room‐temperature determination. A refinement of the ginkgolide A monohydrate structure with Cu Kα data has allowed the assignment of the absolute configuration of the series of compounds. Ginkgolide C sesquihydrate, (1S,2R,3S,3aS,4R,6aR,7aR,7bR,8S,10aS,11S,11aR)‐3‐(1,1‐di­methyl­ethyl)‐hexa­hydro‐2,4,7b,11‐tetrahydroxy‐8‐methyl‐9H‐1,7a‐epoxy­methano‐1H,6aH‐cyclopenta­[c]­furo­[2,3‐b]­furo­[3′,2′:3,4]­cyclo­penta­[1,2‐d]­furan‐5,9,12(4H)‐trione sesquihydrate, C₂₀H₂₄O₁₁·1.5H₂O, has two independent diterpene mol­ecules, both of which exhibit intramolecular hydrogen bonding between OH groups. Ginkgolide J dihydrate, (1S,2R,3S,3aS,4R,6aR,7aR,7bR,8S,10aS,11aS)‐3‐(1,1‐di­methyl­ethyl)‐hexa­hydro‐2,4,7b‐tri­hydroxy‐8‐methyl‐9H‐1,7a‐epoxy­methano‐1H,6aH‐cyclo­penta­[c]­furo­[2,3‐b]furo[3′,2′:3,4]­cyclo­penta­[1,2‐d]­furan‐5,9,12(4H)‐trione dihydrate, C₂₀H₂₄O₁₀·2H₂O, has the same basic skeleton as the other ginkgolides, with its three OH groups having the same configurations as those in ginkgolide C. The conformations of the six five‐membered rings are quite similar across ­ginkgolides A–C and J, except for the A and F rings of ginkgolide A.     

Structural analysis of pyrrolidinones

In the course of a study on pyrrolidinones, the crystal structures of four compounds, namely, methyl N‐[(4‐meth­oxy­phenyl)(3,4,5‐tri­meth­oxy­phenyl)­methyl]­pyro­glut­amate, C₂₃­H₂₇­NO₇, methyl N‐[naphthyl‐(3,4,5‐tri­meth­oxy­phenyl)­methyl]­pyro­glut­amate diacetyl peroxide, C₂₆­H₂₇­NO₆·‐0.5C₄H₆O₄, 5‐(3,4,5‐tri­meth­oxy­phenyl)‐1,2,3,11b‐tetrahy­dro‐5H‐naphtho­[1,8‐f,g]indol­izin‐3‐one, C₂₄­H₂₃­NO₄, and 5‐(3,4,5‐tri­meth­oxy­phenyl)‐1,2,3,5,12,12a‐hexa­hydro­naph­tho­[1,2‐f]indol­izine‐3,12‐dione, C₂₅­H₂₃­NO₅, are presented, compared and discussed.     

Azadirachtol,a tetranortriterpenoid from neem kernels

The title compound, di­methyl (?)‐(2aR,3R,4R,4aS,5R,7aS,8R,10S,10aR)‐3,8,10‐tri­hydroxy‐4‐[(2R,6R)‐2‐hydroxy‐11‐methyl‐5,7,10‐trioxatetra­cyclo­[6.3.1.0^2,60^9,11]­dodec‐3‐en‐9‐yl]‐4‐methyl­per­hydro­isobenzo­furano­[5,4,3a‐cd]­isobenzofuran‐5,10a‐di­acetate, C₂₈H₃₆O₁₃, which exhibits higher antifeedant activity than azadirachtin‐A, a known potent antifeedant, was isolated from neem kernels. The asymmetric unit of the structure contains two independent mol­ecules, which differ in the conformations of their functional groups and also in the conformations of some of the rings. The relative orientation between the decalin and furan­yl moieties is similar to that observed in the majority of azadirachtin structures, but is different from that in azadirachtin‐A. The two symmetry‐independent mol­ecules are linked into dimeric units by intermolecular O—H?O hydrogen bonds.     

New electron‐deficient chiral phosphines: (4R,5R)‐1,3‐bis(trifluoromethanesulfonyl)perhydro‐1,3,2‐benzodiazaphosphol‐2‐yl] substituted amines

Three chiral electron‐deficient phosphine ligands, [(4R,15R)‐,3‐bis­(tri­fluoro­methane­sulfonyl)­per­hydro‐1,3,2‐benzodiazaphosphol‐2‐yl]­diethyl­amine, C₁₂H₂₀F₆N₃O₄PS₂, (IIIa), [(4R,5R)‐1,3‐bis­(tri­fluoro­methane­sulfonyl)­per­hydro‐1,3,2‐benzodi­aza­phosphol‐2‐yl]­di­methyl­amine, C₁₀H₁₆F₆N₃O₄PS₂, (IIIb), and bis­[(4R,5R)‐1,3‐bis­(tri­fluoro­methane­sulfonyl)­per­hydro‐1,3,2‐benzodi­aza­phosphol‐2‐yl]­methyl­amine, (IV), as the chloroform solvate, C₁₇H₂₃F₁₂N₅O₈P₂S₄·0.98CHCl₃, have been prepared from (1R,2R)‐N,N′‐bis­(tri­fluoro­methane­sulfonyl)‐1,2‐cyclo­hexane­di­amine and diethyl phosphor­amido­us dichloride, dimethyl phosphoramidous dichloride or methyl imidodi­phosphorus tetrachloride. The π‐acceptor abilities of these new types of ligands have been evaluated by X‐ray determination of the P—N bond lengths; it has been found that the most promising ligand is the bis­(phosphine) (IV).     

The natural diterpenoid kamebanin

Kamebanin, alternatively called rel‐(?)‐(1R,4R,8S,9R,10S,13S,16R)‐2,8,16‐tri­hydroxy‐5,5,9‐tri­methyl‐14‐methyl­enetetra­cyclo­[11.2.1.0^1,10.0^4,9]­hexadecan‐15‐one, C₂₀H₃₀O₄, is a natural diterpenoid which has cytotoxic and antibacterial activity. The mol­ecule is composed of three six‐membered rings, which all adopt chair conformations, and one five‐membered ring, which adopts an envelope conformation. The conjugated α‐­methyl­ene­cyclo­pentanone ring is the active part in the mol­ecule due to the ring strain. All three hydroxy groups serve as hydrogen‐bond donors and acceptors, forming a continuous two‐dimensional network.     

Simvastatin

Simvastatin, or (1S,3R,7S,8S,8aR)‐8‐{2‐[(2R,4R)‐4‐hydroxy‐6‐oxo‐3,4,5,6‐tetra­hydro‐2H‐pyran‐2‐yl]­ethyl}‐3,7‐di­methyl‐1,2,3,7,8,8a‐hexa­hydro­naphthalen‐1‐yl 2,2‐di­methyl­butan­oate, C₂₅H₃₈O₅, is almost isostructural with lovastatin, and the general conformational features are closely related to those of other reported crystal structures of statins. The only hydrogen bond present facilitates the formation of infinite chains of mol­ecules along the b axis.     

An intermediate in a new synthesis approach to β‐substituted β‐hydroxy­aspartame

The crystal and molecular structure of 1‐tert‐butyl 4‐ethyl (2′R,3′R,5′R,2S,3S)‐3‐bromo­methyl‐3‐hydroxy‐2‐[(2′‐hydroxy‐2′,6′,6′‐tri­methyl­bi­cyclo­[3.1.1]­hept‐3′‐yl­idene)­amino]­succinate, C₂₁H₃₄BrNO₆, is presented. This compound is an intermediate in the new synthetic route to β‐substituted β‐hydroxy­aspartates, which are blockers of glutamate transport.     

The sesquiterpenoid nootkatone and the absolute configuration of a di­bromo derivative

Nootkatone, or (4R,4aS,6R)‐4,4a,5,6,7,8‐hexa­hydro‐4,4a‐di­methyl‐6‐(1‐methyl­ethenyl)­naphthalen‐2(3H)‐one, C₁₅H₂₂O, a sesquiterpene with strong repellent properties against Formosan subterranean termites and other insects, has the valencene skeleton. The di­bromo derivative (1S,3R,4S,4aS,6R,8aR)‐1,3‐di­bromo‐6‐iso­propyl‐4,4a‐di­methyl‐1,2,3,4,5,6,7,8‐octa­hydro­naphthalen‐2‐one, C₁₅H₂₄Br₂O, has two independent mol­ecules in the asymmetric unit, which differ in the rotation of the iso­propyl group with respect to the main skeleton. The C—Br distances are in the range 1.950 (4)–1.960 (4) Å. Both independent molecules form zigzag chains, with very short intermolecular carbonyl–carbonyl interactions, having the perpendicular motif and O⋯C distances of 2.886 (6) and 2.898 (6) Å. These chains are flanked by intermolecular Br⋯Br interactions of distances in the range 4.067 (1)–4.218 (1) Å. The absolute configuration of the di­bromo derivative was determined, from which that of nootkatone was inferred.     

The fungal metabolite austdiol

The title compound, (7R,8S)‐7,8‐di­hydroxy‐3,7‐di­methyl‐6‐oxo‐7,8‐di­hydro‐6H‐isochromene‐5‐carb­aldehyde, C₁₂H₁₂O₅, is a trans‐vicinal diol. Of the two fused rings, which lie approximately in the same plane, the pyran ring is almost perfectly planar, while the cyclo­hexenone ring adopts a slightly distorted half‐chair conformation. The crystal packing is dictated by two strong intermolecular O—H⃛O interactions, one involving hydroxy and keto groups, the other involving two hydroxy groups. Molecules are linked together through twofold axes, forming zigzag ribbons extended along the a axis.     

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.     

A semi‐synthetic analog of the cembranoid sarcophine

The title mol­ecule, 2(R)‐[(1E,3E,7S,8S,11E,13R)‐13‐hydroxy‐4,8,12‐tri­methyl‐7,8‐epoxy­cyclo­tetradeca‐1,3,11‐trien‐1‐yl]­propane‐1,2‐diol, C₂₀H₃₂O₄, is a semi‐synthetic analog of sarcophine, the natural cembranoid of marine origin, isolated from the soft coral Sarcophyton glaucum. The conformation of the 14‐membered ring differs substantially from that of sarcophine. The two OH groups of the propane‐1,2‐diol moiety form an unusual weak intramolecular hydrogen bond with an O⋯O distance of 2.788 (2) Å, and the mol­ecules are linked into double chains by intermolecular hydrogen bonds with O⋯O distances of 2.772 (2) and 2.849 (2) Å.     

Bergenin monohydrate from the rhizomae of Astilbe chinensis

The title compound, 4‐methoxy‐2‐[(1S,2R,3S,4S,5R)‐3,4,5,6‐tetrahydro‐3,4,5‐tri­hydroxy‐6‐(hydroxy­methyl)‐2H‐­pyran‐2‐yl]‐α‐resorcylic acid δ‐lactone monohydrate, C₁₄H₁₆O₉·H₂O, is a C‐glucoside of 4‐O‐methylgallic acid which has antiasthmatic, antitussive, anti‐inflammatory, antifungal, anti‐HIV and antihepatotoxic activity. The mol­ecule is composed of three six‐membered rings: an aromatic ring, a glucopyran­ose ring and an annellated δ‐lactone ring. The glucopyran­ose ring exhibits only small deviations from an ideal chair conformation. The annellated δ‐lactone ring possesses the expected half‐chair conformation. There is one intra‐ and six intermolecular hydrogen bonds which form an extensive hydrogen‐bonding network within the crystal.     

Resolution of (S,S)‐4‐(2,2,4‐tri­methyl­chroman‐4‐yl)­phenyl camphanate and its 4‐chromanyl epimer by crystallization

Dianin's compound (4‐p‐hydroxy­phenyl‐2,2,4‐tri­methyl­chroman) has been resolved by crystallization of the (S)‐(−)‐camphanic esters (S,S)‐ and (R,S)‐4‐(2,2,4‐tri­methyl­chroman‐4‐yl)­phenyl 4,7,7‐tri­methyl‐3‐oxo‐2‐oxabi­cyclo[2.2.1]heptane‐1‐carboxyl­ate, both C₂₈H₃₂O₅, from 2‐methoxy­ethanol, yielding the pure S,S diastereomer. The relative stereochemistry of both diastereomers has been determined by X‐ray crystallography, from which the absolute stereochemistry could be deduced from the known configuration of the camphanate moiety. The crystallographic conformations have been analysed, including the 1:1 disorder of the R,S diastereomer.     

Two (+)‐α,4‐dimethyl‐2‐oxocyclo­hexaneacetic acids: hydrogen bonding in a terpenoid γ‐keto acid and in a diastereomeric lactol

The (+)‐(αS,1S,4R)‐diastereomer of the title structure, C₁₀H₁₆O₃, aggregates in the solid as non‐symmetric dimers with disorder in both carboxyl groups [O·O = 2.710 (5) and 2.638 (5) Å]. The two mol­ecules constituting the asymmetric unit pair around a pseudo‐twofold rotational axis and differ only slightly in their distances and angles, but one methyl group displays rotational disorder absent in the other mol­ecule. Five inter­molecular C—H·O close contacts exist, involving both ketone groups. The (+)‐(αR,1R,4R)‐diastereomer exists in the crystal in its closed‐ring lactol form, (3R,3aR,6R,7aR)‐2,3,3a,4,5,6,7,7a‐octa­hydro‐7a‐hydroxy‐3,6‐dimethyl­benzo[b]furan‐2‐one, C₁₀H₁₆O₃, and aggregates as hydrogen‐bonded catemers that extend from the hydroxyl group of one mol­ecule to the carbonyl group of a neighbor screw‐related along b [O·O = 2.830 (3) Å and O—H·O = 169°]. One close inter­molecular C—H·O contact exists involving the carbonyl group.     

Oxythiamine hexafluorophosphate monohydrate,a thiamine antagonist with the same conformation as ­thiamine

In the title compound, 3‐[(3,4‐di­hydro‐2‐methyl‐4‐oxopyrimidin‐5‐yl)­methyl]‐5‐(2‐hydroxy­ethyl)‐4‐methyl­thia­zolium hexa­fluoro­phosphate monohydrate, C₁₂H₁₆N₃O₂S⁺·PF₆^?·H₂O, oxy­thi­amine is a monovalent cation with a neutral oxo­pyrimidine ring. The mol­ecule assumes the F conformation, which is a common form for thi­amine but which is substantially different from the unusual V conformation found in the chloride and hydro­chloride salts of oxy­thi­amine. The anion‐bridging interaction, C—H?anion?pyrimidine, is emphasized as being important for stabilization of the F conformation.     

2′,3′‐Dehydrosalannol

The title compound, methyl (2aS,3R,5R,5aS,6S,6aS,8R,9aS,10aR,10bR,10cS)‐8‐(3‐furyl)‐2a,4,5,5a,6,6a,8,9,9a,10a,10b,10c‐dodeca­hydro‐3‐hydroxy‐2a,5a,6a,7‐tetra­methyl‐5‐(3‐methylbut‐2‐enoyl­oxy)‐2H,3H‐cyclo­penta­[4′,5′]­furo­[2′,3′:6,5]benzo[cd]­isobenzo­furan‐6‐acetate, C₃₂H₄₂O₈, was isolated from uncrushed green leaves of Azadirachta indica A. Juss (neem) and has been found to possess antifeedant activity against Spodptera litura. The conformations of the functional groups are similar to those of 3‐des­acetyl­salannin, which was isolated from neem kernels. The mol­ecules are linked into chains by intermolecular O—H?O hydrogen bonds.     

Racemic and chiral 1‐[N‐(chloro­acetyl)carbamoylamino]‐2,3‐dihydro‐1H‐inden‐2‐yl chloroacetate

In the racemic crystals of (1S,2R)‐ or (1R,2S)‐1‐[N‐(chloro­acetyl)­carbamoyl­amino]‐2,3‐di­hydro‐1H‐inden‐2‐yl chloro­acetate, C₁₄H₁₄Cl₂N₂O₄, (I), the enantiomeric mol­ecules form a dimeric structure via the N—H?O cyclic hydrogen bond of the carbamoyl moieties. In the chiral crystals of (—)‐(1S,2R)‐1‐[N‐(chloro­acetyl)­carbamoyl­amino]‐2,3‐di­hydro‐1H‐inden‐2‐yl chloro­acetate, C₁₄H₁₄Cl₂N₂O₄, (II), the N—­H?O intermolecular hydrogen bond forms a zigzag chain around the twofold screw axis. The melting points and calculated densities of (I) and (II) are 446 and 396 K, and 1.481 and 1.445 Mg m^?3, respectively.     

Precursors to dodecahedrane

The title compounds, (2R,2′′S,3b′S,4a′R,7b′S,8a′R)‐per­hydro­di­spiro­[furan‐2,3′‐di­cyclo­penta­[a,e]­pentalene‐7′,2′′‐furan]‐5,5′′‐dione, C₂₀H₂₆O₄, and (3aR,3bR,4aR,4bS,5aS,8aR,8bR,9aR,9bS,10aS)‐per­hydro­dipentaleno­[2,1‐a:2′,1′‐e]­pentalene‐1,6‐dione, C₂₀H₂₆O₂, are intermediates identified during the synthesis of dodecahedrane. Crystallographic studies have established the ring‐junction stereochemistry for these important intermediates. All the ring junctions are cis‐fused, and the molecular packing is stabilized by van der Waals interactions.