Plumeridoid C from the Amazonian traditional medicinal plant Himatanthus sucuuba

The stereochemistry of the iridoid plumeridoid C, C₁₅H₁₈O₇, was established by X‐ray single‐crystal structure analysis, giving (2′R,3R,4R,4aS,7aR)‐methyl 3‐hydroxy‐4′‐[(S)‐1‐hydroxyethyl]‐5′‐oxo‐3,4,4a,7a‐tetrahydro‐1H,5′H‐spiro[cyclopenta[c]pyran‐7,2′‐furan]‐4‐carboxylate. The absolute structure of the title compound was determined on the basis of the Flack x parameter and Bayesian statistics on Bijvoet differences. The hydrogen‐bond donor and acceptor functions of the two hydroxy groups are employed in the formation of O—H...O‐bonded helical chains.     

Stereochemical Course of the Formation of the C(7)‐Formyl Group from a Chiral Methyl Group during the Transformation of Chlorophyllide a into Chlorophyllide b

The biosynthesis of chlorophyll a and chlorophyll b from (2R,3R)‐ and (2S,3S)‐5‐amino[2,3‐¹⁴C₂,2,3‐²H₂,2,3‐³H₂]levulinic acid in greening barley has established that chlorophyllide a oxidase catalyses the transformation of the methyl group at C(7) of chlorophyllide a into the CHO group of chlorophyllide b with the loss of H^Si from the 7‐(hydroxymethyl)chlorophyllide intermediate.     

Characterization of novel isobenzofuranones by DFT calculations and 2D NMR analysis

Phthalides are frequently found in naturally occurring substances and exhibit a broad spectrum of biological activities. In the search for compounds with insecticidal activity, phthalides have been used as versatile building blocks for the syntheses of novel potential agrochemicals. In our work, the Diels–Alder reaction between furan‐2(5H)‐one and cyclopentadiene was used successfully to obtain (3aR,4S,7R,7aS)‐3a,4,7,7a‐tetrahydro‐4,7‐methanoisobenzofuran‐1(3H)‐one and (3aS,4R,7S,7aR)‐3a,4,7,7a‐tetrahydro‐4,7‐methanoisobenzofuran‐1(3H)‐one ( 2 ) and (3aS,4S,7R,7aR)‐3a,4,7,7a‐tetrahydro‐4,7‐methanoisobenzofuran‐1(3H)‐one and (3aR,4R,7S,7aS)‐3a,4,7,7a‐tetrahydro‐4,7‐methanoisobenzofuran‐1(3H)‐one ( 3 ). The endo adduct ( 2 ) was brominated to afford (3aR,4R,5R,7R,7aS,8R)‐5,8‐dibromohexahydro‐4,7‐methanoisobenzofuran‐1(3H)‐one and (3aS,4S,5S,7S,7aR,8S)‐5,8‐dibromohexahydro‐4,7‐methanoisobenzofuran‐1(3H)‐one ( 4 ) and (3aS,4R,5R,6S,7S,7aR)‐5,6‐dibromohexahydro‐4,7‐methanoisobenzofuran‐1(3H)‐one and (3aR,4S,5S,6R,7R,7aS)‐5,6‐dibromohexahydro‐4,7‐methanoisobenzofuran‐1(3H)‐one ( 5 ). Following the initial analysis of the NMR spectra and the proposed two novel unforeseen products, we have decided to fully analyze the classical and non‐classical assay structures with the aid of computational calculations. Computation to predict the ¹³C and ¹H chemical shifts for mean absolute error analyses have been carried out by gauge‐including atomic orbital method at M06‐2X/6‐31+G(d,p) and B3LYP/6‐311+G(2d,p) levels of theory for all viable conformers. Characterization of the novel unforeseen compounds ( 4 ) and ( 5 ) were not possible by employing only the experimental NMR data; however, a more conclusive structural identification was performed by comparing the experimental and theoretical ¹H and ¹³C chemical shifts by mean absolute error and DP4 probability analyses. Copyright © 2016 John Wiley & Sons, Ltd.     

Asymmetric Synthesis of Complicated Bicyclic and Tricyclic Polypropanoates via the Double Diels‐Alder Addition of 2,2′‐Ethylidenebis[3,5‐dimethylfuran]

A new, non‐iterative method for the asymmetric synthesis of long‐chain and polycyclic polypropanoate fragments starting from 2,2′‐ethylidenebis[3,5‐dimethylfuran] ( 2 ) has been developed. Diethyl (2E,5E)‐4‐oxohepta‐2,5‐dienoate ( 6 ) added to 2 to give a single meso‐adduct 7 containing nine stereogenic centers. Its desymmetrization was realized by hydroboration with (+)‐IpcBH₂ (isopinocampheylborane), leading to diethyl (1S,2R,3S,4S,4aS,7R,8R,8aR,9aS,10R,10aR)‐1,3,4,7,8,8a,9,9a‐octahydro‐3‐hydroxy‐2,4,5,7,10‐pentamethyl‐9‐oxo‐2H,10H‐2,4a : 7,10a‐diepoxyanthracene‐1,8‐dicarboxylate ((+)‐ 8 ; 78% e.e.). Alternatively, 7 was converted to meso‐(1R,2R,4R,4aR,5S,7S,8S,8aR,9aS,10s,10aS)‐1,8‐bis(acetoxymethyl)‐1,8,8a,9a‐tetrahydro‐2,4,5,7,10‐pentamethyl‐2H‐10H‐2,4a : 7,10a‐diepoxyanthracene‐3,6,9(4H,5H,7H)‐trione ( 32 ) that was reduced enantioselectively by BH₃ catalyzed by methyloxazaborolidine 19 derived from L ‐diphenylprolinol giving (1S,2S,4S,4aS,5S,6R,7R,8R,8aS,9aR,10R,10aS)‐1,8‐bis(acetoxymethyl)‐1,8,8a,9a‐tetrahydro‐6‐hydroxy‐2,4,5,7,10‐pentamethyl‐2H,10H‐2,4a : 7,10a‐diepoxyanthracene‐3,9(4H,7H)‐dione ((−)‐ 33 ; 90% e.e.). Chemistry was explored to carry out chemoselective 7‐oxabicyclo[2.2.1]heptanone oxa‐ring openings and intra‐ring C−C bond cleavage. Polycyclic polypropanoates such as (1R,2S,3R,4R,4aR,5S,6R,7S,8R,9R,10R,11S,12aR)‐1‐(ethoxycarbonyl)‐1,3,4,7,8,9,10,11,12,12a‐decahydro‐3,11‐dihydroxy‐2,4,5,7,9‐pentamethyl‐12‐oxo‐2H,5H‐2,4a : 6,9 : 6,11‐triepoxybenzocyclodecene‐10,8‐carbolactone ( 51 ), (1S,2R,3R,4R,4aS,5S,7S,8R,9R,10R,12S,12aS)‐1,10‐bis(acetoxymethyl)tetradecahydro‐8‐(methoxymethoxy)‐2,4,5,7,9‐pentamethyl‐3,9‐bis{[2‐(trimethylsilyl)ethoxy]methoxy}‐6,11‐epoxycyclodecene‐4a,6,11,12‐tetrol ((+)‐ 83 ), and (1R,2R,3R,4aR,4bR,5S,6R, 7R,8R,8aS,9S,10aR)‐3,5‐bis(acetoxymethyl)‐4a,8a‐dihydroxy‐1‐(methoxymethoxy)‐2,6,8,9,10a‐pentamethyl‐2,7‐bis{[2‐(trimethylsilyl)ethoxy]methoxy}dodecahydrophenanthrene‐4,10‐dione ( 85 ) were obtained in few synthetic steps.     

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.     

Characterization,crystal structure and cytotoxic activity of a rare iridoid glycoside from Lonicera saccata

A new iridoid glycoside, methyl (3R,4R,4aS,7S,7aR)‐3‐hydroxy‐7‐methyl‐5‐oxooctahydrocyclopenta[c]pyran‐4‐carboxylate‐3‐O‐β‐d ‐(1′S,2′R,3′S,4′S,5′R)‐glucopyranoside, named loniceroside A, C₁₇H₂₆O₁₀, ( 1 ), was obtained from the aerial parts of Lonicera saccata. Its structure was established based on an analysis of spectroscopic data, including 1D NMR, 2D NMR and HRESIMS, and the configurations of the chiral C atoms were determined by X‐ray crystallographic analysis. The single‐crystal structure reveals that the cyclopenta[c]pyran scaffold is formed from a five‐membered ring and a chair‐like six‐membered ring connected through two bridgehead chiral C atoms. In the solid state, the glucose group of ( 1 ) plays an important role in constructing an unusual supramolecular motif. The structure analysis revealed adjacent molecules linked together through intermolecular O—H…O hydrogen bonds to generate a banded structure. Furthermore, the banded structures are linked into a three‐dimensional network by interesting hydrogen bonds. Biogenetically, compound ( 1 ) carries a glucopyranosyloxy moiety at the C‐3 position, representing a rare structural feature for naturally occurring iridoid glycosides. The growth inhibitory effects against human cervical carcinoma cells (Hela), human lung adenocarcinoma cells (A549), human acute mononuclear granulocyte leukaemia (THP‐1) and the human liver hepatocellular carcinoma cell line (HepG2) were evaluated by the MTT method.     

Breaking the Mirror: pH‐Controlled Chirality Generation from a meso Ligand to a Racemic Ligand

To study the conversion from a meso form to a racemic form of tetrahydrofurantetracarboxylic acid (H₄L), seven novel coordination polymers were synthesized by the hydrothermal reaction of Zn(NO₃)₂ ? 6 H₂O with (2S,3S,4R,5R)‐H₄L in the presence of 1,10‐phenanthroline (phen), 2,2′‐bipyridine (2,2′‐bpy), or 4,4′‐bipyridine (4,4′‐bpy): [Zn₂{(2S,3S,4R,5R)‐L}(phen)₂(H₂O)] ? 2 H₂O ( 1 ), [Zn₄{(2S,3R,4R,5R)‐L}{(2S,3S,4S,5R)‐L}(phen)₂(H₂O)₂] ( 2 ), [Zn₂{(2S,3S,4R,5R)‐L}(H₂O)₂] ? H₂O ( 3 ), [Zn₄{(2S,3R,4R,5R)‐L}{(2S,3S,4S,5R)‐L} (2,2′‐bpy)₂(H₂O)₂] ? 2 H₂O ( 4 ), [Zn₂ {(2S,3S,4R,5R)‐L}(2,2′‐bpy)(H₂O)] ( 5 ), [Zn₄{(2S,3R,4R,5R)‐L}{(2S,3S,4S,5R)‐L} (4,4′‐bpy)₂(H₂O)₂] ( 6 ), and [Zn₂ {(2S,3S,4R,5R)‐L}(4,4′‐bpy)(H₂O)] ? 2 H₂O ( 7 ). These complexes were obtained by control of the pH values of reaction mixtures, with an initial of pH 2.0 for 1 , 2.5 for 2 , 4 , and 6 , and 4.5 for 3 , 5 , and 7 , respectively. The expected configuration conversion has been successfully realized during the formation of 2 , 4 , and 6 , and the enantiomers of L, (2S,3R,4R,5R)‐L and (2S,3S,4S,5R)‐L, are trapped in them, whereas L ligands in the other four complexes retain the original meso form, which indicates that such a conversion is possibly pH controlled. Acid‐catalyzed enol–keto tautomerism has been introduced to explain the mechanism of this conversion. Complex 1 features a simple 1D metal–L chain that is extended into a 3D supramolecular structure by π–π packing interactions between phen ligands and hydrogen bonds. Complex 2 has 2D racemic layers that consist of centrosymmetric bimetallic units, and a final 3D supramolecular framework is formed by the interlinking of these layers through π–π packing interactions of phen. Complex 3 is a 3D metal–organic framework (MOF) involving meso‐L ligands, which can be regarded as (4,6)‐connected nets with vertex symbol (4⁵.6)(4⁷.6⁸). Complexes 4 and 5 contain 2D racemic layers and (6,3)‐honeycomb layers, respectively, both of which are combined into 3D supramolecular structures through π–π packing interactions of 2,2′‐bpy. The structure of complex 6 is a 2D network formed by 4,4′‐bpy bridging 1D tubes, which consist of metal atoms and enantiomers of L. These layers are connected through hydrogen bonds to give the final 3D porous supramolecular framework of 6 . Complex 7 is a 3D MOF with novel (3,4,5)‐connected (6³)(4².6⁴)(4².6⁶.8²) topology. The thermal stability of these compounds was also investigated.     

The Deoxygenation and Isomerization of Artemisinin and Artemether and Their Relevance to Antimalarial Action

The treatment of artemisinin ( 1 ) and β-artemether ( 6 ) with Zn dissolving in AcOH for a few hours results in mono-deoxygenation giving deoxyartemisinin ( 5 ) and deoxy-β-artemether ( 7 ), respectively, as the sole product. In contrast, submission of 1 to FeCl₂ · 4 H₂O in MeCN at room temperature for 15 min causes only isomerization, (3aS,4R,6aS,7R,10S,10aR)-octahydro-4,7-dimethyl-8-oxo-2H-10H-furo[3,2-i] benzopyran-10-yl acetate ( 8 ) and (3R)-3-hydroxydeoxyartemisinin ( 9 ) being produced in 78 and 17% yield, respectively. The action of FeCl₂ · 4 H₂O in MeCN on 6 is similar. Under the same conditions, 6 gives products analogous to 8 and 9 accompanied by an epimeric mixture of 2-[4-methyl-2-oxo-3-(3-oxobutyl)cyclohexyl]propanaldehyde in yields of 32, 23, and 16%, respectively. No epoxide is formed on repeating the last two experiments in the presence of cyclohexene. The deoxygenation of 1 and 6 by Zn is rationalized in terms of its oxophilic nature. The catalyzed isomerization of 1 and 6 by Fe²⁺ is attributed to the redox properties of the Fe²⁺/Fe³⁺ system.     

Mechanistic and Synthetic Studies on the Formation of 1,2,4-Trioxanes Related to Arteannuin. Photooxygenation of a bicyclic dihydropyran

The photooxygenation of (4R,4aS,7R)-4,4a,5,6,7,8-hexahydro-4,7-dimethyl-3H-2-benzopyran ( 16 ) was performed in (i) MeOH, (ii) acetaldehyde, and (iii) acetone at ?78°. The products obtained respectively were (i) (2R)-2-[(1S,4R)-4-methyl-2-oxocyclohexyl]propyl formate ( 17 ; 72% yield), (ii) 17 (54.5%), (1R,4R,4aS,7R)-3,4,4a,5,6,7-hexahydro-4,7-dimethyl-1H-2-benzopyran-2-yl hydroperoxide ( 19 ; 16.7%), a 12:1 ratio of (3R,4aR,7R,7aS,10R,11aR)-7,7a,8,9,10,11-hexahydro-3,7,10-trimethyl-6H-[2]benzopyrano[1,8a-e]-1,2,4-trioxane ( 20 ) and its C(3)-epimer 21 (17%), together with evidence for the 1,2-dioxetane ( 22 ) originating from the addition of dioxygen to the re-re face of the double bond of 16 , and iii) unidentified products and traces of 22 . Addition of trimethylsilyl trifluoromethanesulfonate (Me₃SiOTf) to the acetone solution of 16 after photooxygenation afforded (4aR,7R,7aS,10R,11aR)-7,7a,8,9,10,11-hexahydro-3,3,7,10-tetramethyl-6H-[2]benzopyrano[1,8a-e]-1,2,4,-trioxane ( 23 , 40%). The photooxygenation of 16 in CH₂Cl₂ at ?78° followed by addition of acetone and Me₃SiOTf afforded 17 (11%), 23 (59%), and (4aR,7R,7aS,10R,11aR)-7,7a,8,9,10,11-hexahydro-3,3,7,10-tetramethyl-6H-[2]benzopyrano[8a,1-e]-1,2,4-trioxane ( 24 ; 5%. Repetition of the last experiment, but replacing acetone by cyclopentanone, gave 17 (16%), (4′aR,7′R,7′aS,10′R,11′aR)-7′,7′a,8′,9′,10′,11′-hexahydro-7′,10′-dimethylspiro[cyclopentane-1,3′-6′H-[2]benzopyrano[1,8a-e]-1,2,4-trixane] ( 25 ; 61%), and (4′aR,7′R,7′aS,10′R,11′aR)-7′,7′a,8′,9′,10′,11′-hexahydro-7′,10′-dimethylspiro[cyclopentane-1,3′-6′H-[2]benzopyrano[8a,1-e]-1,2,4-trixane] ( 26 , 4%). The X-ray analysis of 23 was performed, which together with the NMR data, established the structure of the trioxanes 20, 21, 24, 25 , and 26 . Mechanistic and synthesis aspects of these reactions were discussed in relation to the construction of the 1,2,4-trioxane ring in arteannuin and similar molecules.     

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.     

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.     

Structural and theoretical study of four novel norcantharidine derivatives: two new cases of conditional isomorphism

Structural and theoretical studies of four novel 5,6‐dehydronorcantharidine ( DNCA )/norcantharidine ( NCA ) derivatives, namely (3aR,4S,7R,7aS)‐2‐phenyl‐3a,4,7,7a‐tetrahydro‐4,7‐epoxy‐1H‐isoindole‐1,3(2H)‐dione, C₁₄H₁₁NO₃ ( DNCA‐A ), (3aR,4S,7R,7aS)‐2‐(4‐nitrophenyl)‐3a,4,7,7a‐tetrahydro‐4,7‐epoxy‐1H‐isoindole‐1,3(2H)‐dione, C₁₄H₁₀N₂O₅ ( DNCA‐NA ), (3aR,4S,7R,7aS)‐2‐(4‐nitrophenyl)‐3a,4,5,6,7,7a‐hexahydro‐1H‐4,7‐epoxyisoindole‐1,3(2H)‐dione, C₁₄H₁₂N₂O₅ ( NCA‐NA ), and (3aR,4S,7R,7aS)‐2‐(2‐hydroxyethyl)‐3a,4,5,6,7,7a‐hexahydro‐1H‐4,7‐epoxyisoindole‐1,3(2H)‐dione, C₁₀H₁₃NO₄ ( NCA‐AE ), are reported. The supramolecular interactions and single‐crystal structural characteristics of these molecules, together with the crystal structures of four other similar molecules, i.e. NCA‐A (the 4‐phenyl derivative of NCA‐NA ), DNCA‐AE (the 5,6‐unsaturated derivative of NCA‐AE ), DNCA and NCA , were analysed. Surprisingly, DNCA‐A and NCA‐A , as well as DNCA–NA and NCA‐NA , proved to be isomorphic, while DNCA‐AE and NCA‐AE , as well as DNCA and NCA , have very different crystal structures. These are very rare isostructural examples between unsaturated and saturated oxanorbornene/oxanorbornane derivatives. To further explore how noncovalent interactions (NCIs) affect the degree of isomorphism in this particular series of rigid molecules where there is a fairly limited conformational degree of freedom, all four pairs of crystal structures were analyzed in parallel. The differentiation in NCIs which entails the packing mode of similar molecules is supported by energy calculations based on real or exchanged crystal structures. Our results show that minor structural differences may result in very different supramolecular interactions, and so lead to altered packing modes in the crystalline solids. Even if isostructurality sometimes occurs, the possibility of various molecular packing types cannot be ruled out. On the other hand, isomorphism may just be the result of kinetic possibilities instead of relative thermodynamic stabilities. Though crystal structure prediction is formidable, the comparison method based on existing crystal structures and quantum calculations can be used to predict the probability of isomorphism. This understanding will help us to design new norbornene derivatives with specified structures.     

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.     

The Diastereoselective Formation of 1,2,4-Trioxanes and 1,3-Dioxolanes by the reaction of endoperoxides with chiral cyclohexanones

1,4-Diphenyl-2,3-dioxabicyclo[2.2.1]hept-5-ene ( 2 ), on treatment with a catalytic amount of trimethylsilyl trifluoromethanesulfonate (Me₃SiOTf) in CH₂Cl₂ at ?78°, reacts with excess (?)-menthone ( 10 ) to give (1S,2S,4′aS,5R,7′aS)-4′a,7′a-dihydro-2-isopropyl-5-methyl-6′,7′-diphenylspiro[cyclohexane-1,3′-[7′H]cyclopenta-[1,2,4]trioxine] ( 11 ) and its (1R,2S,4′aR,5R,7′aR)-diastereoisomer 12 in a 1:1 ratio and in 21% yield. Repeating the reaction with 1.1 equiv. of Me₃SiOTf with respect to 2 affords 11 , 12 , and (1S,2S,3′a.R,5R,6′aS)-3′a,6′a-dihydro-2-isopropyl-5-methyl-3′a-phenoxy-5′-phenylspiro[cyclohexane-l,2′-[4′H]cyclopenta[1,3]dioxole] ( 13 ) together with its(1R,2S,3′aS,5R,6′aR)-diastereoisomer 14 in a ratio of 3:3:3:1 and in 56% yield. (+)-Nopinone( 15 ) in excess reacts with 2 in the presence of 1.1 equiv. of Me₃SiOTf to give a pair of 1,2,4-trioxanes ( 16 and 17 ) analogous to 11 and 12 , and a pair of 1,3-dioxolanes ( 18 and 19 ) analogous to 13 and 14 , in a ratio of 8:2:3:3 and in 85% yield. (?)-Carvone and racemic 2-(tert-butyl)cyclohexanone under the same conditions behave like 15 and deliver pairs of diastereoisomeric trioxanes and dioxolanes. In general, catalytic amounts of Me₃SiOTf give rise to trioxanes, whereas 1.5 equiv. overwhelmingly engender dioxolanes. Adamantan-2-one combines with 2 giving only (4′aRS,7′aRS)-4′a,7′a-dihydro-6′.7′a-diphenylspiro[adamantane-2,3′-[7′H]cyclopenta[1,2,4]trioxine] in 98% yield regardless of the amount of Me3SiOTf used. The reaction of 1,4-dipheny 1-2,3-dioxabicyclo[2.2.2]oct-5-ene ( 32 ) with 10 and 1.1 equiv. of Me3SiOTf produces only the pair of trioxanes 33 and 34 homologous to 11 and 12 . Treatment of the (S,S)-diastereoisomer 33 with Zn and AcOH furnishes (1S,2S)-1,4-diphenylcyclohex-3-ene-1,2-diol. The crystal structures of 11 – 13 and 16 are obtained by X-ray analysis. The reaction courses of 10 and the other chiral cyclohexanones with prochiral endoperoxides 2 and 32 to give trioxanes are rationalized in terms of the respective enantiomeric silylperoxy cations which are completely differentiated by the si and re faces of the ketone function. The origin of the 1,3-dioxolanes is ascribed to 1,2 rearrangement of the corresponding trioxanes, which occurs with retention of configuration of the angular substituent.     

Structural diversity in imidazolidinone organocatalysts: a synchrotron and computational study

(S)‐1‐(Methylaminocarbonyl)‐3‐phenylpropanaminium chloride (S2·HCl), C₁₀H₁₅N₂O⁺·Cl⁻, crystallizes in the orthorhombic space group P2₁2₁2₁ with a single formula unit per asymmetric unit. (5R/S)‐5‐Benzyl‐2,2,3‐trimethyl‐4‐oxoimidazolidin‐1‐ium chloride (R3 and S3), C₁₃H₁₉N₂O⁺·Cl⁻, crystallize in the same space group as S2·HCl but contain three symmetry‐independent formula units. (R/S)‐5‐Benzyl‐2,2,3‐trimethyl‐4‐oxoimidazolidin‐1‐ium chloride monohydrate (R4 and S4), C₁₃H₁₉N₂O⁺·Cl⁻·H₂O, crystallize in the space group P2₁ with a single formula unit per asymmetric unit. Calculations at the B3LYP/6–31G(d,p) and B3LYP/6–311G(d,p) levels of the conformational energies of the cation in R3, S3, R4 and S4 indicate that the ideal gas‐phase global energy minimum conformation is not observed in the solid state. Rather, the effects of hydrogen‐bonding and van der Waals interactions in the crystal structure cause the molecules to adopt higher‐energy conformations, which correspond to local minima in the molecular potential energy surface.     

Synthesis of (2S,3R)- and (2S,3S)-[3-H1]-proline via highly stereoselective hydrolysis of a silyl enol ether

A straightforward synthesis of (2S)-[3,3-²H₂]-proline 1c and (2S,3R)- and (2S,3S)-[3-²H₁]-proline, 1b and 1a, respectively, has been devised. The key step of the route to the latter compounds involves highly stereoselective hydrolysis of the silyl enol ethers 3 and 3a, respectively, with protonation (deuteriation) from the re-face of the silyl enol ether.     

Synthesis of Chiral 12-Phenyl(2H)dodecanoic Acids: Useful metabolic probes for the biosynthesis of 1-alkenes from fatty acids

The synthesis of chiral 12-phenyi(²H)dodecanoic acids as metabolic probes for the evaluation of the stereo-chemical course of the biosynthesis of 1-alkerses from fatty acids in plants and insects is described. The diastereoisomeric (2R, 3R)- or (2S, 3S)-12-phenyl(2,3?²H₂)dodecanoic acids 11 are obtained in high chemical and optical yield (>97% e.e.) from the readily available (E)-12-phenyl(2,3-²H₂)dodec-2-enoic acid ( 10 ) or (E)-12-phenyldodec-2-enoic acid ( 10a ) by microbial reduction with wet packed cells of Clostridium tyrobutyricum in either ²H₂O or H₂O buffer. (2R)- and (2S)-12-phenyl(2?²H)dodecanoic acids 9 (>97% e.e.) are accessible from the allylic alcohol 6 via Sharpless epoxidation with (+)-L- or (?)-D-diethyl tartrate, Synthetic routes to the (E)- and (Z)-11-phenyl(1?²H) undec-1-enes 16 and 16a as reference compounds are also included.     

Samaderin B and C from Samadera indica

Samaderin B, or (1R,2S,5R,5aR,7aS,11S,11aS,11bR,14S)‐1,7,7a,11,11a,11b‐hexa­hydro‐1,11‐di­hydroxy‐8,11a,14‐tri­methyl‐2H‐5a,2,5‐(methan­oxy­metheno)­naphth­[1,2‐d]­oxepine‐4,6,10(5H)‐trione, C₁₉H₂₂O₇, and samaderin C, or (1R,2S,5R,5aR,7aS,10S,11S,11aS,11bR,14S)‐7,7a,10,11,11a,11b‐hexa­hydro‐1,10,11‐tri­hydroxy‐8,11a,14‐tri­methyl‐2H‐5a,2,5‐(methan­oxy­metheno)­naphth­[1,2‐d]­oxepine‐4,6(1H,5H)‐dione, C₁₉H₂₄O₇, were isolated from the seed kernels of Samadera indica and were shown to exhibit antifeedant activity against Spodoptera litura third‐instar larvae. The replacement of the carbonyl group in samaderin B by a hydroxy group in samaderin C causes conformational changes at the substitution site, but the overall conformation is not affected; however, the compounds pack differently in the crystal lattice.     

Synthesis and Circular Dichroism of Both Enantiomers of 2-deuterofluoroacetic acid ( Fluoro[2H1]acetic acid)

Sharpless epoxidation of (E)-1-(trimethylsilyl)[1-²H₁]oct-1-en-3-o1 ( 3a ) yielded (1S,2S,3S)- and (1R,2R,3R)-1-(trimethylsilyl)-1,2-epoxy[1-²H₁]octan-3-ols ( 4a and 4b , resp.) which were converted in three steps into (S)- and (R)-fluoro[ ²H₁]acetic acid ( 7a and 7b , resp.) in good yields. Their high isotopic and optical purity was established by ¹H- and ¹⁹F-NMR, mass, and circular-dichroism spectroscopy.     

Metabolism of Deuterated threo‐Dihydroxy Fatty Acids in Saccharomyces cerevisiae: Enantioselective Formation and Characterization of Hydroxylactones and γ‐Lactones

Biotransformation of (±)‐threo‐7,8‐dihydroxy(7,8‐²H₂)tetradecanoic acids (threo‐(7,8‐²H₂)‐ 3 ) in Saccharomyces cerevisiae afforded 5,6‐dihydroxy(5,6‐²H₂)dodecanoic acids (threo‐(5,6‐²H₂)‐ 4 ), which were converted to (5S,6S)‐6‐hydroxy(5,6‐²H₂)dodecano‐5‐lactone ((5S,6S)‐(5,6‐²H₂)‐ 7 ) with 80% e.e. and (5S,6S)‐5‐hydroxy(5,6‐²H₂)dodecano‐6‐lactone ((5S,6S)‐5,6‐²H₂)‐ 8 ). Further β‐oxidation of threo‐(5,6‐²H₂)‐ 4 yielded 3,4‐dihydroxy(3,4‐²H₂)decanoic acids (threo‐(3,4‐²H₂)‐ 5 ), which were converted to (3R,4R)‐3‐hydroxy(3,4‐²H₂)decano‐4‐lactone ((3R,4R)‐ 9 ) with 44% e.e. and converted to ²H‐labeled decano‐4‐lactones ((4R)‐(3‐²H₁)‐ and (4R)‐(2,3‐²H₂)‐ 6 ) with 96% e.e. These results were confirmed by experiments in which (±)‐threo‐3,4‐dihydroxy(3,4‐²H₂)decanoic acids (threo‐(3,4‐²H₂)‐ 5 ) were incubated with yeast. From incubations of methyl (5S,6S)‐ and (5R,6R)‐5,6‐dihydroxy(5,6‐²H₂)dodecanoates ((5S,6S)‐ and (5R,6R)‐(5,6‐²H₂)‐ 4a ), the (5S,6S)‐enantiomer was identified as the precursor of (4R)‐(3‐²H₁)‐ and (2,3‐²H₂)‐ 6 ). Therefore, (4R)‐ 6 is synthesized from (3S,4S)‐ 5 by an oxidation/keto acid reduction pathway involving hydrogen transfer from C(4) to C(2). In an analogous experiment, methyl (9S,10S)‐9,10‐dihydroxyoctadecanoate ((9S,10S)‐ 10a ) was metabolized to (3S,4S)‐3,4‐dihydroxydodecanoic acid ((3S,4S)‐ 15 ) and converted to (4R)‐dodecano‐4‐lactone ((4R)‐ 18 ).