One‐Pot,Asymmetric and Diastereoselective Four‐Component Synthesis of Polyfunctional (Z)‐Alkenyl Methyl Sulfones with Three Stereogenic Centers

The reaction of 1‐(trimethylsilyloxy)cyclopentene ( 9 ) with (±)‐1,3,5‐triisopropyl‐2‐(1‐(RS)‐{[(1E)‐2‐methylpenta‐1,3‐dienyl]oxy}ethyl)benzene ((±)‐ 4a ) in SO₂/CH₂Cl₂ containing (CF₃SO₂)₂NH, followed by treatment with Bu₄NF and MeI gave a 3.0 : 1 mixture of (±)‐(2RS)‐2{(1RS,2Z,4SR)‐2‐methyl‐4‐(methylsulfonyl)‐1‐[(RS)‐1‐(2,4,6‐triisopropylphenyl)ethoxy]pent‐2‐en‐1‐yl}cyclopentanone ((±)‐ 10 ) and (±)‐(2RS)‐2‐{(1RS,2Z)‐2‐methyl‐4‐[(SR)‐methylsulfonyl]‐1‐[(SR)‐1‐(2,4,6‐triisopropylphenyl)ethoxy]pent‐2‐en‐1‐yl}cyclopentanone ((±)‐ 11 ). Similarly, enantiomerically pure dienyl ether (−)‐(1S)‐ 4a reacted with 1‐(trimethylsilyloxy)cyclohexene ( 12 ) to give a 14.1 : 1 mixture of (−)‐(2S)‐2‐{(1S,2Z,4R)‐2‐methyl‐4‐(methylsulfonyl)‐1‐[(S)‐1‐(2,4,6‐triisopropylphenyl)ethoxy]pent‐2‐enyl}cyclohexanone ((−)‐ 13a ) and its diastereoisomer 14a with (1S,2R,4R) or (1R,2S,4S) configuration. Structures of (±)‐ 10 , (±)‐ 11 , and (−)‐ 13a were established by single‐crystal X‐ray crystallography. Poor diastereoselectivities were observed with the (E,E)‐2‐methylpenta‐1,3‐diene‐1‐ylethers (+)‐ 4b and (−)‐ 4c bearing ( 1 S )‐1‐phenylethyl and (1S)‐1‐(pentafluorophenyl)ethyl groups instead of the Greene's auxiliary ((1S)‐(2,4,6‐triisopropylphenyl)ethyl group). The results demonstrate that high α/β‐syn and asymmetric induction (due to the chiral auxiliary) can be obtained in the four‐component syntheses of the β‐alkoxy ketones. The method generates enantiomerically pure polyfunctional methyl sulfones bearing three chiral centers on C‐atoms and one (Z)‐alkene moiety.     

Über Pterinchemie 80. Mitteilung Die Herstellung von (6RS)Tetra- und (6RS)Pentaacetyl-5,6,7,8-tetrahydro-L-bioplerinen

Preparation of (6RS)Tetra- and (6RS)-Pentaacetyl-5,6,7,8-tetrahydro-L-biopterines Boiling of (6RS) l′-O,2′-O,2-N-triacetyl-5,6,7,8-tetrahydro-L-biopterine in acetic anhydride as described in [2], leads to a mixture of the diastereoisomeric (6R)- and (65)-l′-O,2′-O,2-N-,5,8-pentaacetyl-5,6,7,8-L,-biopterines. One of the diastereoisomers can be obtained as pure crystals. It corresponds to the pentaacetate of the natural (6R)- or (6S).,5,6,7,8-tetrahydro-L-biopterine. For the preparation of the earlier described (6RS)- and (6S)-tetraacetyl-tetrahydro-L-biopterines [2] improved conditions are reported.     

Preparation and structural analysis of (±)‐cis‐ethyl 2‐sulfanylidenedecahydro‐1,6‐naphthyridine‐6‐carboxylate and (±)‐trans‐ethyl 2‐oxooctahydro‐1H‐pyrrolo[3,2‐c]pyridine‐5‐carboxylate

Bicycle ring closure on a mixture of (4aS,8aR)‐ and (4aR,8aS)‐ethyl 2‐oxodecahydro‐1,6‐naphthyridine‐6‐carboxylate, followed by conversion of the separated cis and trans isomers to the corresponding thioamide derivatives, gave (4aSR,8aRS)‐ethyl 2‐sulfanylidenedecahydro‐1,6‐naphthyridine‐6‐carboxylate, C₁₁H₁₈N₂O₂S. Structural analysis of this thioamide revealed a structure with two crystallographically independent conformers per asymmetric unit (Z′ = 2). The reciprocal bicycle ring closure on (3aRS,7aRS)‐ethyl 2‐oxooctahydro‐1H‐pyrrolo[3,2‐c]pyridine‐5‐carboxylate, C₁₀H₁₆N₂O₃, was also accomplished in good overall yield. Here the five‐membered ring is disordered over two positions, so that both enantiomers are represented in the asymmetric unit. The compounds act as key intermediates towards the synthesis of potential new polycyclic medicinal chemical structures.     

New neolignan glycosides and a new cerebroside from <Emphasis Type="Italic">Symplocos caudata</Emphasis>

A phytochemical investigation of the roots of Symplocos caudata Wall (Symplocaceae) resulted in the isolation and characterization of two optical isomers of a neolignan glycoside (1) and a new cerebroside (2). Their structures were elucidated as (7R,8S)-erythro-7,9,9'-trihydroxy-3,3',5'-trimethoxy-8-O-4'-neolignan-4-O-β-D-glucopyranoside, (7S,8R)-erythro-7,9,9'-trihydroxy-3,3',5'-trimethoxy-8-O-4'-neolignan-4-O-β-Dglucopyranoside (1), and 1-O-β-D-glucopyranosyl-(2S,3S,4R,8Z,12E)-2-N-[(2'R)-2'-hydroxyheptacosanoyl]-8,12-docosadiene-1,3,4-triol (2), respectively, on the basis of spectroscopic data (1D and 2D NMR, MS and CD).     

SmI2-induced cyclization of optically active (E)- and (Z)-β-alkoxyvinyl sulfoxides with aldehydes

SmI₂-induced reaction of (E)-β-alkoxyvinyl (R)- and (S)-sulfoxides with aldehydes effected a highly stereoselective intramolecular cyclization to give 2,6-anti-2,3-cis- and 2,6-syn-2,3-trans-tetrahydropyran-3-ols, respectively. The reaction of (Z)-(R)-isomer gave 2,6-syn-2,3-cis-tetrahydropyran-3-ol and a ring-opened product, and that of (Z)-(S)-isomer yielded many products.     

Synthesis of All Four Stereoisomers of (E)-Vitamin KT (Phylloquinone), Analysis of Their Diastereoisomeric and Enantiomeric Purities and Determination of Their Biopotencies

All four stereoisomers of (E)-vitamin Kb i. e. (2¹E, ⁷R, 11¹R)-l (= 1a), (2¹E, 7¹ R, l1¹S)-1 (= 1b), (2¹E, 7¹ S, 11¹S) 1 ( = 1c), and (2¹E, 7¹S, 11¹R)-l ( = Id), have been synthesized in a state of high chemical and stereoisomeric purity. The synthesis of stereoisomers lb-d relied on the use of the optically active Cf¹* and C*¹⁰-building blocks (R)- or (S)-4-(benzyloxy)-3-methylbutanal ((R)- or (S)-2) and (R)- or (S)-citronellal ((R)- or (S)- 3 ) which had been secured by the Rh¹-catalyzed allylamine-to-enamine isomerization technology. For the synthesis of the natural (E)-vitamin-K1 stereoisomer 1a , a new route starting from natural phylol was developed, based on an O-alkylation/rearrangement procedure. A HPLC method was developed which separates with remarkable efficiency all four stereoisomers of (E)- as well as three out of the four stereoisomers of (Z)-vitamin K¹ on optically active poly(trityl methacrylate) as the chiral stationary phase supported on Nucleosil. By this method, the stereoisomeric content of the stereoisomers 1b-d synthesized was shown to be in the range of 96-98 %, while the natural isomer 1a was configurationally uniform. The biological activity of the four (E)-vitamin-K₁ stereoisomers was determined by means of the curative prothrombin time test with vitamin-K-depleted chicks. A high precision of the results was obtained with the recently introduced up-and-down organization of the test and the statistical evaluation according to an estimation procedure. With the natural (E)-vitamin-K₁ stereoisomer 1a as standard (set at 1. 0), activities of 0. 93, 1. 19, and 0. 99 were found for stereoisomers 1b, 1c , and 1d , respectively. Within the confidence limits, these activity ratios can be regarded as identical, A very similar efficacy was obtained by comparison of (E, all-rac )-vitamin K₁ ((2¹E, RS, 11′ RS)- 1 ; equimolar mixture of the four stereoisomers 1a-d) with the natural (E)-vitamin-K₁ stereoisomer 1a ). A synergistic effect was not detectable, as was the case with the eight α-tocopheryl-acetate stereoisomers.     

3,6-Thioanhydro sugar derivatives. An enantiospecific synthesis of (2R,3R,4S)-3-benzyloxy-4-hydroxy-2-[(R)-1-benzyloxy-4-hydroxybutyl]thiolane as the key intermediate for thioswainsonine

Methyl 2-O-benzyl-3,6-thioanhydro-α-D-mannopyranoside ( 9 ) was obtained in eight steps from the commercially available methyl α-D-glucopyranoside. Compound 9 was transformed into (2R,3R,4S)-3-benzyloxy-4-hydroxy-2-[(R)-1-benzyloxy-4-hydroxybutyl]thiolane ( 14 ) by acid hydrolysis of its 2,4-di-O-benzyl derivative 10 followed by reaction of the not isolated 2,4-di-O-benzyl-3,6-thioanhydro-D-mannose ( 11 ) with ethoxycarbonylmethylenetriphenylphosphorane to give an = 1:1 E/Z mixture of the corresponding α,β-unsaturated ester ( 12 ). Finally, catalytic hydrogenation of 12 to ethyl (R)-4-benzyloxy-4-[(2′R)3′R,4′S)-3′-benzyloxy-4′-hydroxythiolan-2′-yl]butanoate ( 13 ) and subsequent reduction with lithium aluminum hydride gave the title compound 14 .     

Stereoselektive Totalsynthese von natürlichem Phytol und Phytolderivaten und deren Verwendung zur Herstellung von natürlichem Vitamin K1

Steroselective Total Synthesis of Natural Phytol and Derivatives thereof; Use of these Compounds in the Synthesis of Natural Vitamin K₁ The Li₂CuCl₄-catalyzed couplings of the easily accessible bifunctional C₅ allylic acetates (E)- 18a and (E)- 18b with racemic hexahydrofarnesylmagnesium bromide ((3 RS/RS, 7 RS/SR)- 19a ) proceed with high chemo- and stereoselectivity (≥98% (E)-retention) to give the (2E, 7 RS/RS, 11 RS/SR)-phytol derivatives 1a and 1b , respectively, in yields of 72–80% (Scheme 5). The same couplings performed with optically active hexahydrofarnesylmagnesium bromide (3 R, 7 R)- 19a yielded the (E)-phytol derivatives of the natural series (7 R, 11R)- 1a and (7 R, 11 R)- 1b. Acid-catalyzed hydrolysis of(2 E, 7 R, 11 R)- 1b gave natural phytol((2 E, 7 R, 11 R)- 1c ) Friedel-Crafts alkylation of ‘menadiol monobenzoate’ 11b with (2 E, 7 R, 11 R)- 1a or (2 E, 7 R, 11 R)- 1b gave the dihydrovitamine K₁ derivative (2 E/Z, 7′ R, 11′R)- 12b ((E/Z)≈? 9:l). Conversion of configurationally pure (2 E, 7′ R, 11′ R)- 12b (yield 73%; obtained after chromatographic removal of the (Z)-isomer) into natural vitamine K₁ ((2 E,7′ R, 11′ R)- 2 ) was achieved in the usual way by saponification and oxidation with air. Some further investigations of the coupling reactions of bifunctional C₅ allylic synthons with hexahydrofarnesylmagnesium bromide (3 RS/RS, 7 RS/SR)- 19a showed the outcome of these reactions to be critically dependent on the nature of the leaving group, the double-bond geometry and the nature and concentration of the catalyst. Thus, the Li₂CuCl₄-catalyzed couplings of (3 RS/RS,7 RS/SR)- 19a with the allylic halides 29a and 29c as well as with p-toluenesulfonate 29b yielded besides the phytol derivatives 1a and 1b - also the S_N2′-type products 30a and 30b (Scheme 8, Table 2); the same result was found for the coupling with the cis-configurated allylic acetates (Z)- 18a and (Z)- 18b (Table 3). A similar loss of chemo selectivity as well as the loss of stereoselectivity in the coupling reactions of 19 with the bifunctional (E)-olefins of type 18 was observed when the Li₂CuCl₄-catalyst concentration was increased from 0.2 to 25 mol-% or upon substitution of Li₂CuCl₄ by copper (I) chloride or iodide (Table 4).     

A study on the sulfenylchlorination of cembrene and the related cembranoids

p-Tolylsulfenyl chloride adds regioselectively at the C(11) ? C(12) bond of cembrene 1 to give 11-(R)-p-tolylthio-1-(S)-cembra-2E, 4Z, 7E, 12(20)-tetraene 2 following a rapid HCl elimination. Two new cembranoids, 1-(S)-cembra-2E, 4Z, 7E, 12(20)-tetraene 3 and 1-(S)-cembra-2E, 4Z, 7E, 11Z-tetraen-20-ol 4 are prepared from 2.     

A new ceramide from the root of <Emphasis Type="Italic">Isatis Indigotica</Emphasis> and its cytotoxic activity

In addition to two ceramides 1-O-β-D-glucopyranosyl-(2S,3R)-N-(2'-hydroxyhexadecanoyl)-octadeca-4E,8Esphingenine (2) and (2S,3S,4R)-N-(2'-hydroxytetracosanoyl)-octadecasphingenine (3), which separated for the first time, a new ceramide 1-O-β-D-glucopyranosyl-(2S,3R)-N-(2'-hydroxyhexacosanoyl)octadecasphingenine (1) was isolated from the traditional Chinese medicinal herb Isatis indigotica. Their cytotoxic effects were evaluated by the MTT method.     

(all-E)-12′-Apozeaxanthinol,Persicaxanthine und Persicachrome

( all-E)-12′-Apozeanthinol, Persicaxanthine, and Persicachromes Reexamination of the so-called ‘persicaxanthins’ and ‘persicachromes’, the fluorescent and polar C₂₅-apocarotenols from the flesh of cling peaches, led to the identification of the following components: (3R)-12′-apo-β-carotene-3,12′-diol ( 3 ), (3S,5R,8R, all-E)- and (3S,5R,8S,all-E)-5,8-epoxy-5,8-dihydro-12′-apo-β-carotene-3,12′-diols (4 and 5, resp.), (3S,5R,6S,all-E)-5,6-epoxy-5,6-dihydro-l2′-apo-β-carotene-3,12′-diol =persicaxanthin; ( 6 ), (3S,5R,6S,9Z,13′Z)-5,6-dihydro-12′apo-β-carotene-3,12′-diol ( 7 ; probable structure), (3S,5R,6S,15Z)-5,6-epoxy-5,6-dihydro-12′-apo-β-carotene-3,12′-diol ( 8 ), and (3S,5R,6S,13Z)-5,6-epoxy-5,6-dihydro-12′-apo-β-carotene-3,12′-diol ( 9 ). The (Z)-isomers 7 – 9 are very labile and, after HPLC separation, isomerized predominantly to the (all-E)-isomer 6 .     

Azimine IV. Kinetik und Mechanismus der thermischen Stereoisomerisierung von 2,3-Diaryl-1-phthalimido-aziminen

Azimines IV. Kinetics and Mechanism of the Thermal Stereoisomerization of 2,3-Diaryl-1-phthalimido-azimines¹) Mixtures of (1E, 2Z)- and (1Z, 2E)-2-phenyl-1-phthalimido-3-p-tolyl-azimine ( 3a and 3b , resp.) and (1E, 2Z)- and (1Z, 2E)-3-phenyl-1-phthalimido-2-p-tolylazimine ( 4a and 4b , resp.) were obtained by the addition of oxidatively generated phthalimido-nitrene (6) to (E)- and (Z)-4-methyl-azobenzene ( 7a and 7b , resp.). Whereas complete separation of the 4 isomers 3a, 3b, 4a and 4b was not possible, partial separation by chromatography and crystallization led to 5 differently composed mixtures of azimine isomers. The spectroscopic properties of these mixtures (UV., ¹H-NMR.) were used to determine the ratios of isomers in the mixtures, and served as a tool for the assignment of constitution and configuration to those isomers which were dominant in each of these mixtures, respectively. Investigation of the isomerization of the azimines 3a, 3b, 4a and 4b within the 5 mixtures at various concentrations by ¹H-NMR.-spectroscopy at room temperature revealed that only stereoisomers are interconverted ( 3a ? 3b; 4a ? 4b) and that the (1E, 2Z) ? (1Z, 2E) stereoisomerization is a unimolecular reaction. These observations exclude an isomerization mechanism via an intermediate 1-phthalimido-triaziridine (2) or via dimerization of 1-phthalimido-azimines (1) , respectively. The 3-p-tolyl substituted stereoisomers 3a and 3b isomerized slightly slower than the 3-phenyl substituted ones 4a and 4b , an effect which is consistent with the assumption that the rate determining step of the interconversion of (1E, 2Z)- and (1Z, 2E)-1-phthalimido-azimines (1a ? 1b) is the stereoisomerization of the stereogenic center at N(2), N(3), either by inversion of N(3) or by rotation around the N(2), N(3) bond. The total isomerization process is assumed to occur via the thermodynamically less stable (1Z, 2Z)- and (1E, 2E)-isomers 1c and 1d , respectively, as intermediates in undetectably low concentrations which stay in rapidly established equilibria with the observed, thermodynamically more stable (1E, 2Z)- and (1Z, 2E)-isomers 1a and 1b , respectively. At higher temperatures, the azimines 3 and 4 are transformed into N-phenyl-N,N′-phthaloyl-N′-p-tolyl-hydrazine (8) with loss of nitrogen.     

Supramolecular Photochirogenesis. 3. Enantiodifferentiating Photoisomerization of Cyclooctene Included and Sensitized by 6-O-Mono(o-methoxybenzoyl)–cyclodextrin

Supramolecular enantiodifferentiating photoisomerization of (Z)-cyclooctene (1Z) to chiral (E)-isomer (1E) through inclusion and sensitization by 6-O-mono(o-methoxybenzoyl)--cyclodextrin (2) was investigated in water and in aqueous methanol solutions at various temperatures. A dramatic inversion of the product chirality was observed to occur by simply changing the solvent from water to methanol. Thus, the supramolecular photosensitization in aqueous solution gave (R)-(–)-1E in 15% enantiomeric excess (ee), whereas in methanol the antipodal (S)-(+)-1E was obtained in 5% ee. The temperature and solvent dependencies of the product ee are discussed.     

Isolation,structural elucidation and cytotoxicity evaluation of a new pentahydroxy-pimarane diterpenoid along with other chemical constituents from Aerva lanata

Aervalanata possesses various useful medicinal and pharmaceutical activities. Phytochemical investigation of the plant has now led to the isolation of a new 2α,3α,15,16,19-pentahydroxy pimar-8(14)-ene diterpenoid (1) together with 12 other known compounds identified as β-sitosterol (2), β-sitosterol-3-O-β-D-glucoside (3), canthin-6-one (4), 10-hydroxycanthin-6-one (aervine, 5), 10-methoxycanthin-6-one (methylaervine, 6), β-carboline-1-propionic acid (7), 1-O-β-D-glucopyranosyl-(2S,3R,8E)-2-[(2′R)-2-hydroxylpalmitoylamino]-8-octadecene-1,3-diol (8), 1-O-(β-D-glucopyranosyl)-(2S,3S,4R,8Z)-2-[(2′R)-2′-hydroxytetracosanoylamino]-8(Z)-octadene-1,3,4-triol (9), (2S,3S,4R,10E)-2-[(2′R)-2′-hydroxytetracosanoylamino]-10-octadecene-1,3,4-triol (10), 6′-O-(4″-hydroxy-trans-cinnamoyl)-kaempferol-3-O-β-D-glucopyranoside (tribuloside, 11), 3-cinnamoyltribuloside (12) and sulfonoquinovosyldiacylglyceride (13). Among these, six compounds (8–13) are reported for the first time from this plant. Cytotoxicity evaluation of the compounds against five cancer cell lines (CHO, HepG2, HeLa, A-431 and MCF-7) shows promising IC₅₀ values for compounds 4, 6 and 12.     

Asymmetric Total Synthesis of (11R, 12S, 13S, 9Z, 15Z)-9, 12, 13-Trihydroxyoctadeca-9, 15-dienoic Acid,a self-defensive agent against rice-blast disease

The Diels-Alder adduct of furan and 1-cyanovinyl (1′R)-camphanate was converted into methyl [(tert-butyl)-dimethylsilyl 5-deoxy-2, 3-O-isopropylidene-β-L -ribo-hexofuranosid] uronate ((+)- 4 ). Reduction with diisobutyl-aluminium hydride gave the corresponding aldehyde which was condensed with the ylide derived from triphenyl-(propyl)phosphonium bromide to give (1R, 2S, 3S, 4S)-1-[(tert-butyl)dimethylsilyloxy]tetrahedro-2, 3-(isopropyl-idenedioxy)-4-[(Z)-pent-2′ -enyl]furan ((+)- 7 ). Removal of the silyl protective group gave a mixture of the corresponding furanose that underwent Wittig reaction with the ylide derived from [8-(methoxycarbonyl)-octyl]triphenylphosphonium bromide to yield methyl (11R, 12S, 13S, 9Z, 15Z)-13-hydroxy-11, 12-(isopropylidene-dioxy)octadeca-9, 15-dienoate ((?)- 9 ). Acidic hydrolysis, then saponification afforded (11R, 12S, 13S, 9Z, 15Z)-11, 12, 13-trihydroxyoctadeca-9, 15-dienoic acid ( 1 ).     

Total Synthesis of All Eight Stereoisomers of α-Tocopheryl Acetate. Determination of their diastereoisomeric and enantiomeric purity by gas chromatography

All eight stereoisomers of α-tocopheryl acetate have been synthesized in a state of high chemical and stereoisomeric purity. Key chiral side-chain intermediates were prepared from (+)-(S)-3-hydroxy-2-methylpropanoic acid. New routes to (2R, 4′ RS, 8′ RS)-α-tocopheryl acetate, a mixture of four diastereoisomers, were also developed. A sensitive gas chromatographic method was developed to determine the diastereoisomeric and enantiomeric purity of α-tocopherol samples as the methyl ethers. It was established for the first time that naturally occurring α-tocopherol is essentially a single enantiomer (2 R, 4′ R, 8′ R), synthetic all-rac-α-tocopherol an equimolar mixture of four racemates, and that natural (E)-(7 R, 11 R)-phytol is diastereoisomerically and enantiomerically homogeneous.     

Preparation and Olfactory Characterization of the Enantiomerically Pure Isomers of the Perfumery Synthetic Galaxolide®

The commercially important isochromane musk odorant Galaxolide^® (=1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylcyclopenta[g]-2-benzopyran; HHCB; 3 ) was separated into its diastereoisomers via the tricarbonyl(η⁶-cyclopenta[g]-2-benzopyran)chromium complexes 10 . Since GC/olfactometry indicated that only one enantiomer of each diastereoisomer (4RS,7RS)- 3 and (4RS,7SR)- 3 determines the odor characteristics of the commercial product, all four stereoisomers (4S,7R)-, (4S,7S)-, (4R,7S)-, and (4R,7R)- 3 were synthesized by Friedel-Crafts alkylation of 1,1,2,3,3-pentamethylindane ( 11 ) with (S)- and (R)-methyloxirane ((S)- and (R)- 12 , resp.), acid-catalyzed reaction of the resulting products with paraformaldehyde, and separation of the formed diastereoisomer pairs via the tricarbonyl(η⁶-cyclopenta[g]-2-benzopyran)chromium complexes 10 . The powerful musk odor of Galaxolide ^® ( 3 ) was thus attributed to its (−)-(4S)-isomers (4S,7R)- and (4S,7S)- 3 , while the (+)-(4R)-isomers (4R,7S)- and (4R,7R)- 3 were weak to almost odorless.     

Über Pterinchemie. 85. Mitteilung. Polyacetylierte 5,6,7,8-Tetrahydro-D- und -L-neopterine. Ein besonderer Fall von N(5)-Alkylierung des 5,6,7,8-Tetrahydroneopterin-Gerüstes

Polyacetylated 5,6,7,8-Tetrahydro-D - and L -neopterins. A Special Case of N(5)-Alkylation of 5,6,7,8-Tetrahydroneopterins Improved conditions are reported for the preparation of the earlier described (6R)- and (6S)-1′-O,2′-O,3′-O,2-N,5-pentaacetyl-5,6,7,8-tetrahydro-L -neopterins, one of which could be obtained as pure crystals. Its structure, determined by X-ray-diffraction analysis, corresponds to the (6R)-enantiomer. The method has also been used to make the corresponding D -diastereoisomers. Further acetylation of (6RS)-1′-O,2′-O,3′-O,2-N-tetraacetyl-5,6,7,8-tetrahydro-D -neopterin under drastic conditions yields a mixture of several polyacetylated D -neopterin derivatives and a polyacetylated ethyl-tetrahydro-D -neopterin which was isolated in crystalline form and established by X-ray-diffraction analysis to be (6R)-1′-O,2′-O,3′-O,4-O,2-N,2-N,8-heptaacetyl-5-ethyl-5,6,7,8-tetrahydro-D -neopterin.     

A Note on Stereochemical Observations of the Deprotonation of Ethyl 2-Alkenoates

Deprotonation of ethyl (E)-2-alkenoates 1 , 3 and 4 yields after protonation the double bond migrated (3 Z)-isomers 5 , 7 and 9 as major products. In contrast, deprotonation and reprotonation of ethyl (Z)-2-pentenoate ( 2 ) gives the (3 E)-isomer 6 exclusively. These findings are explained by reaction paths starting from different ester conformations.     

Conformations of Z- and E-isomers of some chiral (1R,4R)-2-arylidene-p-menthan-3-ones

The ¹Í NMR method in combination with molecular simulation was used to study conformations of Z- and E-isomers of (1R,4R)-cis-2-(4-methoxyphenyl)benzylidene-p-menthan-3-one. In solutions the Z-isomer, unlike the conformationally uniform Å-isomer, is an equilibrium mixture of chair conformers with the substantial predomination of one form with the axially oriented methyl and equatorial isopropyl groups (75—78%). The enone group is more nonplanar in the Z-isomer than in the Å-isomer. For the isopropyl fragment, the equiprobable existence of trans- and two gauche-rotamers for the Z-isomer and a substantial predomination of gauche-forms in the case of the E-isomer were established.