Chirale Synthesebausteine durch Kolbe-Elektrolyse enantiomerenreiner β-Hydroxy-carbonsäurederivate. (R)- und (S)-Methyl-sowie (R)-Trifluormethyl-γ-butyrolactone und -δ-valerolactone

Chiral Building Blocks for Syntheses by Kolbe Electrolysis of Enantiomerically Pure β-Hydroxybutyric-Acid Derivatives. (R)- and (S)-Methyl-, and (R)-Trifluoromethyl-γ-butyrolactones, and -δ-valerolactones The coupling of chiral, non-racemic R* groups by Kolbe electrolysis of carboxylic acids R*COOH is used to prepare compounds with a 1.4- and 1.5-distance of the functional groups. The suitably protected β-hydroxycarboxylic acids (R)- or (S)-3-hydroxybutyric acid, (R)-4,4,4-trifluoro-3-hydroxybutyric acid (as acetates; see 1 – 6 ), and (S)-malic acid (as (2S,5S)-2-(tert-butyl)-5-oxo-1,3-dioxolan-4-acetic acid; see 7 ) are decarboxylatively dimerized or ‘codimerized’ with 2-methylpropanoic acid, with 4-(formylamino)butyric acid, and with monomethyl malonate and succinate. The products formed are derivatives of (R,R)-1,1,1,6,6,6-hexafluoro-2,5-hexanediol (see 8 ), of (R)-5,5,5-trifluoro-4-hydroxypentanoic acid (see 9,10 ), of (R)- and (S)-5-hydroxyhexanoic acid (see 11 ) and its trifluoro analogue (see 12, 13 ), of (S)-2-hydroxy- and (S,S)-2,5-dihydroxyadipic acid (see 23, 20 ), of (S)-2-hydroxy-4-methylpentanoic acid (‘OH-leucine’, see 21 ), and of (S)-2-hydroxy-6-aminohexanoic acid (‘OH-lysine’, see 22 ). Some of these products are further converted to CH₃- or CF₃-substituted γ- and δ-lactones of (R)- or (S)-configuration ( 14 , 16 – 19 ), or to an enantiomerically pure derivative of (R)-1-hydroxy-2-oxocyclopentane-1-carboxylic acid (see 24 ). Possible uses of these new chiral building blocks for the synthesis of natural products and their CF₃ analogues (brefeldin, sulcatol, zearalenone) are discussed. The olfactory properties of (R)- and (S)-δ-caprolactone ( 18 ) are compared with those of (R)-6,6,6-trifluoro-δ-caprolactone ( 19 ).     

Uncommon Sesquiterpenoids and New Triterpenoids from Jatropha neopauciflora (Euphorbiaceae)

Eight new terpenoids ( 1 – 8 ) were isolated from the bark of Jatropha neopauciflora, together with eight known compounds. The new isolates include the sesquiterpenoids (1R,2R)‐diacetoxycycloax‐4(15)‐ene ( 1 ); (1R,2R)‐dihydroxycycloax‐4(15)‐ene ( 2 ), (2R)‐δ‐cadin‐4‐ene‐2,10‐diol ( 3 ), (2R)‐δ‐cadina‐4,9‐dien‐2‐ol ( 4 ), (1R,2R)‐dihydroxyisodauc‐4‐en‐14‐ol ( 5 ) and its acetonide 6 (artifact), as well as the two triterpenoids (3β,16β)‐16‐hydroxylup‐20(29)‐en‐3‐yl (E)‐3‐(4‐hydroxyphenyl)prop‐2‐enoate ( 7 ) and (3β,16β)‐16‐hydroxyolean‐18‐en‐3‐yl (E)‐3‐(4‐hydroxyphenyl)prop‐2‐enoate ( 8 ). The structures of these compounds were established by extensive 1D‐ and 2D‐NMR spectroscopic methods, and their absolute configurations were determined by circular‐dichroism (CD) experiments, and by X‐ray crystallographic analysis (compound 7 ; Fig. 3). A plausible biosynthesis of the sesquiterpenoids 1 – 5 is proposed (Scheme), starting from (?)‐germacrene D as the common biogenetic precursor.     

Three New, 1‐Oxygenated ent‐8,9‐Secokaurane Diterpenes from Croton kongensis

Three new ent‐8,9‐secokaurane diterpenes, kongensins A–C ( 1 – 3 ), were isolated from the aerial parts of Croton kongensis, together with two known compounds, rabdoumbrosanin ( 4 ) and (7α,14β)‐7,14‐dihydroxy‐ent‐kaur‐16‐en‐15‐one ( 5 ). The structures of the new compounds were elucidated by HR‐MS as well as in‐depth 1D‐ and 2D‐NMR analyses. Compounds 1 – 3 showed an unusual oxygenation pattern, with an AcO or OH group at C(1), in combination with a Δ⁸⁽¹⁴⁾ unsaturation ( 1 ) or an 8,14‐epoxide function ( 2, 3 ).     

Synthesis,Structure, and Photophysical Properties of the Di‐ and Trinuclear Phosphine‐Diimine Complexes of Copper(I)

Reactions of [Cu(NCMe)₄]⁺ with stoichiometric amount of diphosphine R₂P–(C₆H₄)_n–PR₂, (R = NC₄H₄, n = 1; R = Ph, n = 1, 2, 3) or tri‐phosphine 1, 3, 5‐(PPh₂–C₆H₄–)₃–C₆H₃ ligands give the corresponding di‐ or trinuclear copper(I) acetonitrile‐phosphine complexes 1 – 5 . Substitution of the labile acetonitrile groups with chelating aromatic diimines – 2, 2′‐bipyridine (bpy), 1, 10‐phenanthroline (phen), 5, 6‐dimethyl‐1, 10‐phenanthroline (dmp), 5, 6‐dibromo‐1, 10‐phenanthroline (phenBr₂) – gives the corresponding substituted compounds 6 – 16 . In all complexes 1 – 16 each central Cu^I atom has tetrahedral configuration completed with two N‐ and two P‐donor groups. The compounds obtained were characterized using elemental analysis, ESI‐MS, X‐ray crystallography, and NMR spectroscopy. All phosphine‐diimine compounds 6 – 16 are photoluminescent at room temperature both in dichloromethane solution and in solid state (λ_ex = 385 nm). In CH₂Cl₂ solution the maxima of emission bands are found in a range 540–640 nm, and in solid in a similar range 538–620 nm. Emission of 6 – 16 is assigned to the triplet excited state dominated by the charge transfer transitions with contribution of the MLCT character.     

Konfigurations- und konformationsisomere paratrope,rotationsdynamische Tetraepoxy[32]annulene(6.2.6.2) und diatrope Tetraoxa[30]porphyrin(6.2.6.2)-Dikationen : Nachweis eines Tetraepoxy[31]annulen(6.2.6.2)-Radikalkations

Configurational and Conformational Isomeric Paratopic, Rotational Dynamics Tetraepoxy[30]annulenes(6.2.6.2) and Diatropic Tetraoxa[30]porphyrin(6.2.6.2) Dications: Detection of a Tetraepoxy[31]annulene(6.2.6.2)Radical Cation The synthesis of tetraepoxy[32]annulenes(6.2.6.2) ( 4 ) by a cyclizing twofold Wittig reaction of (E,E,E)-5,5′-(hexa-1,3,5-triene-1,6-diyl)bis[furan-2-carbaldehyde] ( 6 ) and the corresponding bis-phosphonium salt 7 is described (Scheme 1). Contrary to the configuration of the educts, the obtained annulenes 4a and 4b are (Z,E,E,E,Z,E,E,E)- and (E,Z,E,E,E,Z,E,E)-configurated, respectively. The ¹H-NMR spectra establish the paratropic, antiaromatic character of 4 . The annulenes 4 are highly dynamic systems, the (E)-ethenediyl bridges rotate around the adjacent σ-bonds, these rotations are frozen at −80°. The McMurry condensation of dialdehyde 6 yields the (E,E,Z,E,E,E,Z)-4,5-dihydrotetraepoxy[32]annulene(6.2.6.2) ( 13a ), where the configuration of the dialdehyde 6 – beside the hydrogenated double bond – is retained. As result of an intramolecular McMurry reaction of 6 , (Z,E,Z,Z)-dioxa[16]annulene(6.2) 14 is formed. By oxidation of the [32]annulenes(6.2.6.2) 4a and 4b , a mixture of the four stereoisomeric tetraoxa[30]porphyrin(6.2.6.2) dications 5a / 5a ′/ 5b / 5c is obtained; the configuration of the isomers is determined by COSY, NOESY, and NOE experiments. The Δδ values (26.81, 25.83, and 21.11 ppm) underline the diatropic, aromatic character of the dications 5 , the Soret bands are shifted bathochromically to 550 nm, and the Q-bands are in the NIR region (896 – 1039 nm). The dihydroannulene 13a is dehydrogenated by p-chloroanil (tetrachloro-1,4-benzoquinone) to give the annulenes 4a and 4b , its oxidation with DDQ (=4,5-dichloro-3,6-dioxocyclohexa-1,4-diene-1,2-dicarbonitrile) results in the same mixture of dications 5 . Entirely different results are obtained by reaction of the dihydroannulene 13a with DDQ. Here, the (E,E,E,Z,E,E,E,Z) tetraoxa[30]porphyrin(6.2.6.2) dication 5c – formed only in traces from 4a / 4b – is the main product. Beside 5c , a by-product (3%) can be isolated, which turns out (ESR, conductivity) to be the (E,E,E,Z,E,E,E,Z)-tetraoxa[31]porphyrin(6.2.6.2) radical cation 16 , obviously the intermediate in the oxidation sequence of the annulene to the dication. This result leads to the conclusion that the reaction of the dihydro compound 13a with p-chloroanil and DDQ follows different reaction mechanisms. For all isolated stereoisomeric tetraepoxy annulenes and tetraoxaporphyrin dications, the ΔH_f values are calculated by the semiempiric AM1 method. The results are in agreement with the experimental observations. All data confirm the antiaromaticity of the tetraepoxy[32]annulenes(6.2.6.2) 4 and the aromaticity of the tetraoxa[30]porphyrin(6.2.6.2) dications.     

Photoisomerization of 2H,6H-thiin-3-one 1-oxides to 3H,7H-[1,2]oxathiepin-4-ones

Oxidation of 2H, 6H-thiin-3-ones 1a – c with 3-chloroperbenzoic acid affords the corresponding 1-oxides 2a – c . On irradiation (350 nm) in either benzene or MeCN, these cyclic sulfoxides 2 isomerize to 3H, 7H-1,2-oxathiepin-4-ones 3 . The tetramethyl derivative 3a is isolated by flash chromatography at ?10°, but, at higher temperatures, it undergoes ring contraction and H₂O elimination to give 4,4-dimethyl-2(2-methylprop-2enylidene)thietan-3-one ( 4 ). Diemthyloxathiepinones 3b and 3c undergo ring contraction in MeOH to afford 1-(4-methylthiophen-2-yl)ethanone ( 5 ) and two diastereoisomeric 4,4-dimethyl-2-methoxy-2-(1-methoxyethyl)thietan-3-ones ( 6 and 7 , respectively).     

Lignanoids and Diterpenoids from Callicarpa furfuraceae

The three new lignanoids 1 – 3 and the five new phyllocladane diterpenoids 7 – 11 were isolated from the leaves of Callicarpa furfuraceae, together with two known lignanoids, lariciresinol ( 4 ) and (+)‐sesamin ( 5 ), and five known diterpenoids, 17‐norphyllocladane‐3,16‐dion ( 6 ), calliterpenone ( 12 ), calliterpenone 17‐acetate ( 13 ), (3β,16α)‐phyllocladane‐3,16,17‐triol ( 14 ), and (3β,16α)‐phyllocladane‐3,16,17‐triol 17‐acetate ( 15 ). Their structures were established by spectral‐data interpretation.     

Nucleotides,Part LXIII,New 2-(4-Nitrophenyl)ethyl(Npe)- and 2-(4-Nitrophenyl)ethoxycarbonyl(Npeoc)-Protected 2′-Deoxyribonucleosides and Their 3′-Phosphoramidites – Versatile Building Blocks for Oligonucleotide Synthesis

A series of new base-protected and 5′-O-(4-monomethoxytrityl)- or 5′-O-(4,4′-dimethoxytrityl)-substituted 3′-(2-cyanoethyl diisopropylphosphoramidites) and 3′-[2-(4-nitrophenyl)ethyl diisopropylphosphoramidites] 52 – 66 and 67 – 82 , respectively, are prepared as potential building blocks for oligonucleotide synthesis (see Scheme). Thus, 3′,5′-di-O-acyl- and N ²,3′-O,5′-O-triacyl-2′-deoxyguanosines can easily be converted into the corresponding O⁶-alkyl derivatives 6 , 8 , 10 , 12 , 14 , and 16 by a Mitsunobu reaction using the appropriate alcohol. Mild hydrolysis removes the acyl groups from the sugar moiety (→ 9 , 11 , 13 , 15 , and 19 (via 18 ), resp.) which can then be tritylated (→ 38 – 42 ) and phosphitylated (→ 57 – 61 ) in the usual manner. N ²-[2-(4-nitrophenyl)ethoxycarbonyl]-substituted and N ²-[2-(4-nitrophenyl)ethoxycarbonyl]-O⁶-[2-(4-nitrophenyl)ethyl]-substituted 2′-deoxyguanosines 5 and 7 , respectively, are synthesized as new starting materials for tritylation (→ 28 , 35 , and 37 ) and phosphitylation (→ 54 , 56 , 70 , and 78 ). Various O⁴-alkylthymidines (see 20 – 24 ) are also converted to their 5′-O-dimethoxytrityl derivatives (see 43 – 47) and the corresponding phosphoramidites (see 62 – 66 and 79 – 82 ).     

Reduktion von 1,2-bis[(Z)-(2-nitrophenyl)-NNO-azoxy]benzol: Synthese von Cyclotrisazobenzol ( = (5E,6aZ,11E,12aZ,17E,18aZ)-5,6,11,12,17,18-Hexaazatribenzo[aei][1,3,5,7,9,11]cyclododeca-hexaen)

Reduction of 1,2-Bis[(Z)-(2-nitrophenyl)-NNO-azoxy]benzene¹: Synthesis of Cyclotrisazobenzene ( = (5E,6aZ,11E,12aZ,17E,18aZ)-5,6,11,12,17,18-Hexaazatribenzo[aei][1,3,5,7,9,11]cyclododeca-hexaene) Na₂S reduction of 1,2-bis[(Z)-(2-nitrophenyl)-NNO-azoxy]benzene ( 2 ) yielded 3 deoxygenated products: the (known) red 2,2′-((E,E)-1,2-phenylenbisazo)dianiline ( 3 , 23%), the orange 2-[2-((E)-2-aminophenylazo)phenyl]-2H-benzotriazol ( 4 , 55%) and the colorless 2,2′-(1,2-phenylene)di-2H-benzotriazol ( 5 , 13%). The constitutions of 3 – 5 and of 6 , the N-acetyl derivative of 4 , were deduced from their ¹H-NMR spectra (chemical shifts, couplings, and symmetry properties), and the configurations of 3 , 4 , and 6 at their N,N-double bonds are assumed to be the same as in 2 . Oxidation of 3 with 2 mol-equiv. of Pb(OAc)₄ afforded 5 (47%) and a novel, highly symmetrical macrocycle, called cyclotrisazobenzene ( 7 , 24%). The constitution of 7 as a tribenzo-hexaaza[12]annulene and its (E)-configuration at the N,N-bonds was confirmed by X-ray analysis. The molecular symmetry expressed by the ¹H-, ¹³C- and ¹⁵N-NMR spectra of 7 reveals a rapid torsional motion around the six N,C bonds. This implies that the N,N-double bonds in the cyclic 12π-electron system (or 24π-electron system if the benzene rings are included) of 7 are highly localized.     

Isolation from the Mediterranean Stolonifern Coral Sarcodictyon roseum of Sarcodictyin C,D, E,and F,novel diterpenodic alcohols esterified by (E)- or (Z)-N(1)-methylurocanic acid. Failure of the carbon-skeleton type as a classification criterion

It is shown here that the stoloniferan coral Sarcodictyon roseum of east Pyrenean waters contains four novel diterpenoids, sarcodictyin C ((?) -3 ), D ((?) -4 ), E ((+)- 5 ), F ((+)- 6 ), which are related to sarcodictyin A ( = (?)-(4R,4aR,7R,10S,11S,12aR,1Z,5E,8Z-7,10-epoxy-3,4,4a,7,10,11,12,12a-octahydro-7-hydroxy-6-(methyoxycarbonyl)-1,10-dimethyl-4-(1-methylethyl)-benzocyclodecen-11-yl (E)-N¹-methylyrocanate; ((?)? 1 ), previously isolated from the same coral. Sarcodictyin C ((?) -3 ) and D ((?) -4 ) and the 3α-hydroxy and 3α-acetoxy derivatives of (?) -1 ), sarcodictyin E ((+) -5 ) is the (Z)-urocanate isomer of (?) -3 ), and sarcodictyin F ((+) -6 ) is the 1α-hydroxy-2-ene isomer of (?) -3 . In all cases, the nine-membered ring is locked, and the molecule stabilized, by the urocanic appendage; when this is removed in MeOH/KOH, the C(11)–O^? function is free to attack at C(5), and retro-condensations then lead to the ring-contracted butenolides 11 (from (?) -3 ) or 10 (from(?) -1 ) with extrusion of the hydroxyfuran nucleus (Scheme 3). Under the same conditions, with (?) -3 , the C(3)-O^? group competitively attacks at C(5), the hydroxyfuran nucleus is expelled, and aldehyde 14 is formed. Peculiarly, in the reaction of (?) -3 with MeOD/KOD, the ring-contracted butenolide 17 contains D at the 4′-ax position. The sarcodictyins are unique in these chemical properties, not shared by the cladiellanes which have the same C-skeleton.     

Synthesis of cannabinoid model compounds. Part 2: (3R, 4R)-Δ1(6)-Tetrahydrocannabinol-5″-oic acid and 4″(R,S)-Methyl-(3R, 4R)-Δ1(6)-tetrahydrocannabinol-5″-oic Acid

Two novel cannabinoid model compounds, (3R, 4R)-Δ¹⁽⁶⁾-tetrahydrocannabinol-5″-oic acid (22) and 4″(R, S)-methyl-(3R, 4R)-Δ¹⁽⁶⁾-tetrahydrocannabinol-5″-oic acid (23) were synthesized by acid-catalyzed condensation of (+)-trans-p-mentha-2, 8-dien-l-ol (1) with the substituted resorcinols 18 and 19 obtained by a Wittig reaction between 3, 5-bis(benzyloxy)benzaldehyde (7) and methyl 4-bromobutanoate (10) or methyl 4-bromo-2(R, S)-methylbutanoate (11) resp. with subsequent hydrogenation. The resulting methyl esters 20 and 21 were hydrolyzed to give acids 22 and 23 .     

Mono- and Dialkylation of Derivatives of (1R, 2S)-2-Hydroxycyclopentanecarboxylic Acid and -cyclohexanecarboxylic acid via bicyclic dioxanones: Selective generation of three contiguous stereogenic centers on a cyclohexane ring

Ethyl (1R, 2S)-2-hydroxycyclopentanecarboxylate and -cyclohexanecarboxylate ( 1a and 2a , respectively) obtained in 40 and 70% yield by reduction of 3-oxocyclopentanecarboxylate and cyclohexanecarboxylate, respectively (Scheme 2), with non-fermenting yeast, are converted to bicyclic dioxanone derivatives 3 and 4 with formaldehyde, isobutyraldehyde, and pivalaldehyde (Scheme 3). The Li-enolates of these dioxanones are alkylated (→ 5a – 5i , 5j , 6a – 6g ), hydroxyalkylated (→ 51, m, 6d, e ), acylated (→ 5k, 6c ) and phenylselenenylated (→ 7 – 9 ) with usually high yields and excellent diastereoselectivities (Scheme 3, Tables and 2). All the major isomers formed under kinetic control are shown to have cis-fused bicyclic structures. Oxidation of the seleno compounds 7–9 leads to α, β-unsaturated carbonyl derivatives 10 – 13 (Scheme 3) of which the products 12a – c with the C?C bond in the carbocyclic ring (exocyclic on the dioxanone ring) are most readily isolated (70–80% from the saturated precursors). Michael addition of Cu(I)-containing reagents to 12a – c and subsequent alkylations afford dioxanones 14a – i and 16a – d with trans-fused cyclohoxane ring (Scheme 4). All enolate alkylations are carried out in the presence of the cyclic urea DMPU as a cosolvent. The configuration of the products is established by NMR measurements and chemical correlation. Some of the products are converted to single isomers of monocyclic hydroxycyclopentane ( 17 – 19 ) and cyclohexane derivatives ( 20 – 23 ; Scheme 5). Possible uses of the described reactions for EPC synthesis are outlined. The observed steric course of the reactions is discussed and compared with that of analogous transformations of monocyclic and acyclic derivatives.     

Four New Pregnane Steroids from Aglaia abbreviata and Their Cytotoxic Activities

Four new pregnane steroids, aglaiasterols A–D ( 1 – 4 ), have been isolated from the EtOH extract of stems of Aglaia abbreviata. They were identified as (3α,5α,17Z)‐3‐hydroxypregn‐17‐en‐16‐one ( 1 ), (3β,5α,17E)‐3‐hydroxypregn‐17‐en‐16‐one ( 2 ), (3β,5α,17Z)‐3‐hydroxypregn‐17‐en‐16‐one ( 3 ), and (3α,5α,20S*)‐3‐hydroxy‐16‐oxopregnan‐20‐yl acetate ( 4 ) on the basis of spectroscopic methods, including 1D‐ and 2D‐NMR techniques. Compounds 1 – 4 were evaluated for their cytotoxic activities against K562 (human leukemia), MCF‐7 (human breast cancer), and KB (human oral epithelium cancer) cells, and drug‐resistant cells of K562/A02, MCF‐7/ADM, and KB/VCR. These isolates showed weak to moderate inhibitory effects on the growth of the tested cell lines.     

Asymmetrische Michael-Additionen. Stereoselektive Alkylierung chiraler,nicht racemischer Enolate durch Nitroolefine. Herstellung enantiomerenreiner γ-Aminobuttersäure- und Bernsteinsäure-Derivate

Asymmetric Michael-Additions. Stereoselective Alkylation of Chiral, Non-racemic Enolates by Nitroolefins. Preparation of Enantiomerically Pure γ-Aminobutyric and Succinic Acid Derivatives Chiral, non-racemic lithium enolates ( E , F , G ) of 1,3-dioxolan-4-ones, methyl 1,3-oxazolidin-4-carboxylates, methyl 1,3-oxazolin-4-carboxylates, 1,3-oxazolidin-5-ones, and 1,3-imidazolidin-4-ones derived from (S)-lactic acid ( 2a ), (S)-mandelic acid ( 2b ), and (S)-malic acid ( 2c ), or from (S)-alanine ( 10 ), (S)-proline ( 11 ), (S)-serine ( 12 ), and (S)-threonine ( 13 ), are added to nitroolefins. Michael adducts ( 3 – 9 , 14 – 18 ) are formed (40–80%) with selectivities generally above 90% ds of one of the four possible stereoisomers. Conversions of these nitroalkylated products furnish the α-branched α-hydroxysuccinic acids 28 and 29 , the α-hydroxy-γ-amino acid 25 , the α,γ-di-amino acid 32 , the substituted γ-lactames 19 – 22 , and the pyrrolidine 23 . The relative and absolute configuration of the products from dioxolanones and nitropropene are derived by chemical correlation and NOE measurements indicating that the steric course of reaction is to be specified as 1k, ul-1,3. The mechanism is discussed.     

Oligonucleotide Analogues with Integrated Bases and Backbone. Part 28

The protected hydrazide‐linked uracil‐ and adenine‐derived tetranucleoside analogues 17, 19 , and 21 were synthesized in solution by coupling the dimeric hydrazines 6 and 10 with the carboxylic acids 7, 11 , and 16 . These hydrazines and acids were obtained by partially deprotecting the hydrazines 5, 9 , and 15 , and these were prepared by coupling the hydrazines 3 and 14 with the carboxylic acids 4 and 8 . The crystal structure analysis of the fully protected UU dimer 5 showed the formation of an antiparallel cyclic duplex with the uracil units H‐bonded via H? N(3) and O?C(2). Stacking interactions were observed between the uracil units with a buckle twist of 30.9°, and between the uracil unit II and the fluoren‐9‐yl group of Fmoc (=9H‐fluoren‐9‐yl)methoxycarbonyl). The hydrazide H? N(3′) and the C?O group of Fmoc form an intramolecular H‐bond. The uracil‐ and adenine‐derived, water‐soluble hydrazide‐linked self‐complementary octamers 23 – 32 and the non‐self‐complementary uracil derived decamer 33 were obtained by coupling the carboxylic acids 4 and 8 on a solid support. ¹H‐NMR Analysis in CDCl₃, mixtures of CDCl₃ and (D₆)DMSO, and (D₈)THF showed that the partially deprotected dimers 5, 6, 12 , and 13 form weakly associated linear duplexes. The partially deprotected tetramers 17 and 18 do not associate. The hydrazide‐linked octamers 23 – 32 do not stack in aqueous solution, and the non‐self‐complementary decamer 33 does not stack with the complementary strands of DNA 43 and RNA 42 . The Cbz‐protected amide‐linked octamers 51 – 56 derived from uracil, adenine, cytosine, and guanine were obtained as the main products by solid‐phase synthesis from the carboxylic acids 46 – 49 . The fully deprotected amide‐linked octamers proved insoluble, and could neither be purified nor analysed.     

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.     

Huangqiyenins G – J,Four New 9,10‐Secocycloartane (=9,19‐Cyclo‐9,10‐secolanostane) Triterpenoidal Saponins from Astragalus membranaceus Bunge Leaves

Four new 9,10‐secocycloartane (=9,19‐cyclo‐9,10‐secolanostane) triterpenoidal saponins, named huangqiyenins G–J ( 1 – 4 , resp.), were isolated from Astragalus membranaceus Bunge leaves. The acid hydrolysis of 1 – 4 with 1M aqueous HCl yielded D ‐glucose, which was identified by GC analysis after treatment with L ‐cysteine methyl ester hydrochloride. The structures of 1 – 4 were established by detailed spectroscopic analysis as (3β,6α,10α,16β,24E)‐3,6‐bis(acetyloxy)‐10,16‐dihydroxy‐12‐oxo‐9,19‐cyclo‐9,10‐secolanosta‐9(11),24‐dien‐26‐yl β‐D ‐glucopyranoside ( 1 ), (3β,6a,10α,24E)‐3,6‐bis(acetyloxy)‐10‐hydroxy‐12,16‐dioxo‐9,19‐cyclo‐9,10‐secolanosta‐9(11),24‐dien‐26‐yl β‐D ‐glucopyranoside ( 2 ), (3β,6α,9α,10α,16β,24E)‐3,6‐bis(acetyloxy)‐9,10,16‐trihydroxy‐9,19‐cyclo‐9,10‐secolanosta‐11,24‐dien‐26‐yl β‐D ‐glucopyranoside ( 3 ), and (3β,6α,10α,24E)‐3,6‐bis(acetyloxy)‐10‐hydroxy‐16‐oxo‐9,19‐cyclo‐9,10‐secolanosta‐9(11),24‐dien‐26‐yl β‐D ‐glucopyranoside ( 4 ).     

Reversed Stereochemical Course of the Michael Addition of Cyclohexanone to β-Nitrostyrenes by Using 1-(Trimethylsiloxy)cyclohexene/Dichloro(diisopropoxy)titanium. Preliminary Communication

Induced by a stoichiometric excess of dichloro(diisopropoxy)titanium, 1-(trimethylsiloxy)cyclohexene and p-substituted β-nitrostyrenes (Y = H,CH₃,CH₃O,CN) combine in CH₂Cl₂ solution at ?90° preferentially with relative topicity ul – opposite to the corresponding reaction of enolates or enamines. The primary products are the bicyclic nitronates 3–5 which can be separated, and which are cleaved by KF in MeOH to give the aryl(nitroethyl)-substituted cyclohexanones 1 and 2 (Tables 1 and 2, two typical procedures are given). The major products (2:1 to 4:1) are the hitherto not readily available diastereoisomers 2 of l-configuration. Instead of being solvolyzed, the bicyclic nitronate 5 can be used for nitroaldol additions (→ 6 ) and for [3 + 2]-dipolar cycloadditions (→ 7 ), diastereoselectively furnishing products with 4 asymmetric C-atoms (not counting acetal centers). The Michael addition described here is yet another example of an ul-combination of trigonal centers induced by Lewis acids, overriding the influence of the configuration of the donor component.     

Synthesis of Chiral Starburst Dendrimers from PHB-Derived Triols as Central Cores

Chiral triols 1 – 3 (‘tris(hydroxymethyl)methane’ derivatives), prepared from (R)-3-hydroxybutanoic acid and aldehydes, are used as center pieces of dendrimers. The triols may be employed as such or after attachment of spacers containing alkyl or aryl moieties (see 5 and 7 ). The branches combined with the original or elongated triols are those first reported by Fréchet ( 9 – 12 , benzyl ethers of 3,5-dihydroxybenzyl alcohol and bromide). In this way, 1st-, 2nd-, and 3rd-generation chiral dendrimers without ( 13 – 15 ), or with aliphatic ( 16 – 18 ) or aromatic ( 19 – 21 ) spacers are prepared. The molecular weights range from 447 to 2716 Dalton. Two of the chiral triols, i.e., 2 and 3 , are used as center pieces for chiral dendrimers containing 6 NH₂, or 6 and 12 NO₂ groups on the periphery ( 22 – 27 ), with 3,5-dinitrobenzoyl chloride as the branching unit. All compounds thus synthesized are of course monodisperse and are fully characterized. In some cases, the optical activity of the dendrimers indicates that conformationally chiral substructures might be present. The NH₂- and NO₂-substituted compounds avidly clathrate smaller molecules; they are sorbents exchanging host molecules through the gas phase.     

2-Alkyliden-1, 3-dithia-Heterocyclen aus 5-Sulfonyl-1, 2-dithiol-3-onen und Alkoholaten

Asymmetrically substituted 5-sulfonyl-1, 3-dithiafulvenes (9a–g), all of which have the same configuration (called α), are obtained by reaction of 4-chloro-5-sulfonyl-1, 2-dithiol-3-ones (3a–e) with sodium alkoxides. Side-products formed are 4-chloro-5-alkoxy-1, 2-dithiol-3-ones (5a and 5b), 3, 5-bis-alkylidene-1, 2, 4-trithiacyclopentanes (21 and 22), and (in some instances) minor amounts of compounds 33, 34, or 35. Reaction of 4-phenyl-5-methylsulfonyl-1, 2-dithiol-3-one with sodium methoxide results in the formation of 4-phenyl-5-methoxy-1, 2-dithiol-3-one (5c), the two cis-trans-isomers of 2, 4-bis-alkylidene-1, 3-dithiacyclobutane 24 and 25, and the 2, 5-bis-alkylidene-1, 2, 4, 5-tetrathiacyclohexane 26. Some conceivable reaction mechanisms are discussed, and proof is given for the structure of the major compounds. By treating 4-chloro-5-(2′-chloro-ethylthio)-1, 2-dithiol-3-one with sodium methoxide, the 2-alkylidene-1, 3-dithiolane 13 is obtained. The sulfonyl groups of the 1, 3-dithiafulvenes 9a–g described may be easily replaced by hydrogen or secondary amines, yielding compounds 14, 16 and 19, respectively. When dissolved in strong acids and reprecipitated, asymmetrically substituted 2-alkylidene-1, 3-dithia compounds may be converted into mixtures of all possible cis-trans-isomers thereof. Those isomers may be separated by fractional crystallization. Isomers 31 (called β) of 9 a--g, and 32 of 16a, b, are obtained accordingly.