Oligosaccharide Analogues of Polysaccharides. Part 12. Synthesis of ‘acetyleno-saccharide’-derived cyclodextrin analogues

‘Acetyleno-oligosaccharides’ in which two terminal ethynyl substituents enclose an angle (significantly) below 180° are building blocks for the preparation of cyclodextrin analogues. This is illustrated by the preparation of a cyclotrimer and a cyclotetramer; the C₃-symmetrical cyclotrimer 18 (Scheme 1) was synthesized in 13 steps (7.7%) and the C₄-symmetrical cyclotetramer 51 (Scheme 3) in 14 steps (4.3%) from the known dialkyne 21. The solubilities of 18 and 51 in H₂O were determined by gravimetry; a saturated solution is 130 mM in the trimer 18 and 12.8 mM in the tetramer 51 . The dependence of the optical rotation of 18 and 51 in H₂O on the concentration, and the concentration dependence of the ¹H-NMR chemical shift of the signals of the ¹CH groups of 51 (D₂O) suggest that there is no significant self-association of 18 and 51 .     

Oligosaccharide Analogues of Polysaccharides. Part 4. Synthesis of a monosaccharide-derived octamer

NaSMe in toluene leads to regioselective de-C-silylation of the bis[(trimethylsilyl)ethynyl]saccharide 2 , but to decomposition of butadiynes such as 1 or 12 . We have, therefore, combined the known reagent-controlled, regioselective desilylation of 2 and of 12 (AgNO₂/KCN) with a substrate-controlled regioselective de-C-silylation, based on C-silyl groups of different size. This combination was studied with the fully protected 3 which was mono-desilylated to 4 or to 5 (Scheme 1). Triethylsilylation of 5 (→ 6 ) was followed by removal of the Me₃Si group (→ 7 ), introduction of a (t-Bu)Me₂Si group (→ 8 ) and removal of the Et₃Si group yielded 9 ; these high-yielding transformations proceed with a high degree of selectivity. Iodination of 4 gave 10 . The latter was coupled with 5 to the homodimer 11 and the heterodimer 12 , which was desilylated to 13 . The second building block for the tetramer was obtained by coupling 14 (from 7 ) with 5 , leading to 15 and 16 . Removal of the Me₃Si group (→ 17 ) and iodination led to 18 which was coupled with 13 to the homotetramer 20 and the heterotetramer 19 (Scheme 2). Deprotection of 19 gave 21 , which was, on the one hand, iodinated to 22 , and, on the other hand, protected by the (t-Bu)Me₂Si group (→ 23 ). Removal of the Et₃Si group (→ 24 ) and coupling afforded the homooctamer 26 and the heterooctamer 25 . Yields of iodination, silylation, and desilylation were consistently high, while heterocoupling proceeded in only 50–55%. Cleavage of the (i-Pr)₃SiC and MeOCH₂O groups of 11 (→ 27 ), 15 (→ 28 ), 20 (→ 29 ) and 26 (→ 30 ) proceeded in high yields (Scheme 3). Complete deprotection in two steps of the heterocoupling products 16 (→ 31 → 32 ), 19 (→ 33 → 34 ), and 25 (→ 35 → 36 ) gave the unprotected dimer 32 , tetramer 34 , and octamer 36 in high yields (Scheme 4). Only the dimer 32 is soluble in H₂O; the ¹H-NMR spectra of 32 , 34 , and 36 in (D₆)DMSO (relatively low concentration) show no signs of association.     

Oligosaccharide Analogues of Polysaccharides

The cellobiose-derived dimer 18 , tetramer 48 , and octamer 49 have been prepared. Acetolytic debenzylation transformed the dimer 15 , obtained from the partially benzylated, dialkynylated cellobiose 2 (Scheme 1), into 16 that was deacetylated to 18 (Scheme 2), but the analogous debenzylation of the tetramer 14 proved unsatisfactory. We, therefore, avoided benzyl groups and prepared the cellobiose-derived monomer 32 by glycosidation of 27 with the crystalline trichloroacetimidates 30 or 31 (Scheme 3). The acceptor 27 was synthesised from 1,6-anhydroglucose in 7 steps (48% overall yield), and the trichloroacetimidates 30 and 31 were obtained in good overall yields from the alkynylated glucopyranoses 29 (Scheme 3). The structure of the anomeric trichloroacetimidates 30 and 31 was determined by single crystal X-ray analysis. The alkyne 34 , orthogonally C-protected by SiMe₃ and GeMe₃ groups, was transformed by a binomial strategy into the dimer 37 , the tetramer 41 , and the octamer 47 (Scheme 4). The unprotected mono- and oligomers 1 , 18 , 48 , and 49 are soluble in H₂O, MeOH, and DMSO. Their ¹H-NMR specta ((D₆)DMSO ( 1 , 18 , 48 , 49 ), CD₃OD ( 1 , 18 , 48 ), D₂O ( 49 )) show no signs of association.     

Oligonucleotide Analogues with Integrated Bases and Backbone. Part 14

The self‐complementary tetrameric propargyl triols 8, 14, 18 , and 21 were synthesized to investigate the duplex formation of self‐complementary, ethynylene‐linked UUAA, AAUU, UAUA, and AUAU analogues with integrated bases and backbone (ONIBs). The linear synthesis is based on repetitive Sonogashira couplings and C‐desilylations (34–72% yield), starting from the monomeric propargyl alcohols 9 and 15 and the iodinated nucleosides 3, 7, 11 , and 13 . Strongly persistent intramolecular H‐bonds from the propargylic OH groups to N(3) of the adenosine units prevent the gg‐type orientation of the ethynyl groups at C(5′). As such, an orientation is required for the formation of cyclic duplexes, this H‐bond prevents the formation of duplexes connected by all four base pairs. However, the central units of the UAUA and AAUU analogues 18 and 14 associate in CDCl₃/(D₆)DMSO 10 : 1 to form a cyclic duplex characterized by reverse Hoogsteen base pairing. The UUAA tetramer 8 forms a cyclic UU homoduplex, while the AUAU tetramer 21 forms only linear associates. Duplex formation of the O‐silylated UUAA and AAUU tetramers is no longer prevented. The self‐complementary UUAA tetramer 22 forms Watson–Crick‐ and Hoogsteen‐type base‐paired cyclic duplexes more readily than the sequence‐isomeric AAUU tetramer 23 , further illustrating the sequence selectivity of duplex formation.     

Oligosaccharide Analogues of Polysaccharides,Part 21 , Towards New Cellulose I Mimics: Synthesis of Dialkynyl C‐glucosides of peri‐Substituted Anthraquinone

The bis‐C‐glucoside 2 has been synthesised as the first representative of a series of templated glucosides and cellooligosaccharides that mimick part of the unit cell of cellulose I. As expected, there are, at best, weakly persistent H‐bonds between the two glucosyl residues in (D₆)DMSO and (D₇)DMF solution. The acetylated oct‐1‐ynitol 7 and deca‐1,3‐diynitol 12 were prepared from the gluconolactone 5 (Scheme 1). Coupling of 12 to PhI and 2‐iodothiophene yielded 13 and 14 , respectively, while dimerisation of the benzylated and acetylated deca‐1,3‐diynitols 10 and 12 afforded the bis‐C‐glucosyloctatetrayne 15 and the less stable 16 , respectively. The 2‐glucosylthiophene 17 was obtained by treating the C‐silylated deca‐1,3‐diynitol 9 with Na₂S. Cross‐coupling of (trimethylsilyl)acetylene (TMSA) with 1,8‐bis(triflyloxy)‐9,10‐anthraquinone ( 20 ) at elevated temperature gave the dialkynylated 21 ; its structure was established by X‐ray analysis (Scheme 2). Sequential coupling of 6 or 7 and TMSA to 20 gave the symmetric dialkyne 21 , the mixed dialkynes 23 (from 6 ) and 25 (from 7 ), and the symmetric diglucoside 36 (from 7 ) in modest yields; a stepwise coupling to the acetylated monotriflate 28 proved advantageous. It led to the oct‐1‐ynitol 29 and the deca‐1,3‐diynitol 33 that were transformed into the triflates 30 and 34 , respectively. Coupling of the triflate 34 to the oct‐1‐ynitol 7 gave the unsymmetric bis‐C‐glucoside 35 ; this was obtained in higher yields by coupling the triflate 30 to the deca‐1,3‐diynitol 12 . Coupling of the bistriflate 20 with either 7 or 12 afforded the symmetric bis‐C‐glucosides 36 and 37 , respectively. Deacetylation (KCN in MeOH) of 35 – 37 provided the unsymmetric bis‐C‐glucoside 2 and the symmetric analogues 3 and 4 .     

Oligonucleosides with a Nucleobase‐Including Backbone. Part 11

A linear and a convergent synthesis of uridine‐derived backbone‐base‐dedifferentiated (backbone including) oligonucleotide analogues were compared. The Sonogashira cross‐coupling of the alkyne 1 and the iodide 2 gave the dimer 4 that was C‐desilylated and again coupled with 2 to give the trimer 6 (Scheme 1). Repeating this linear sequence led to the pentamer 10 . Coupling yields were satisfactory up to formation of the trimer 6 , but decreased for the coupling to higher oligomers. Similarly, coupling of the alkynes 5, 7 , and 9 with the iodouridine 3 gave, in decreasing yields, the trimer 12 , tetramer 13 , and pentamer 14 , respectively. The dimeric iodouracil 20 was synthesized by coupling the alkyne 17 with the iodide 16 to the dimer 18 , followed by iodination at C(6/I) to 19 and O‐silylation (Scheme 2). The iodinated dimer 23 was prepared by iodinating and O‐silylating the known dimer 21 . Coupling of 20 and 23 with the dimer 5 , trimer 7 , and tetramer 9 gave the tetramers 8 and 13 , the pentamers 10 and 14 , and the hexamer 15 , respectively (Scheme 3). The oligomers up to the pentamer 14 were deprotected to provide the trimer 24 , tetramer 25 , and pentamer 26 (Scheme 4). There was no evidence for the heteropairing of the pentamer 26 and rA₇ , nor for the pairing of rU₅ and rA₇, while a UV melting experiment showed the beginning of a sigmoid curve for the interaction of rU₇ with rA₇. Therefore, the pentamer 26 does not pair more strongly with rA₇ than rU₅.     

Photochemische Reaktionen 111. Mitteilung [1] Zur Photochemie α, β-ungesättigter γ, δ-Epoxyester I: Singulett- versus Triplettreaktivität

On triplet excitation (E)- 2 isomerizes to (Z)- 2 and reacts by cleavage of the C(γ), O-bond to isomeric δ-ketoester compounds ( 3 and 4 ) and 2,5-dihydrofuran compounds ( 5 and 19 , s. Scheme 1). - On singulet excitation (E)- 2 gives mainly isomers formed by cleavage of the C(γ), C(δ)-bond ( 6–14 , s. Scheme 1). However, the products 3–5 of the triplet induced cleavage of the C(γ), O-bond are obtained in small amounts, too. The conversion of (E)- 2 to an intermediate ketonium-ylide b (s. Scheme 5) is proven by the isolation of its cyclization product 13 and of the acetals 16 and 17 , the products of solvent addition to b . - Excitation (λ = 254 nm) of the enol ether (E/Z)- 6 yields the isomeric α, β-unsaturated ε-ketoesters (E/Z)- 8 and 9 , which undergo photodeconjugation to give the isomeric γ, δ-unsaturated ε-ketoesters (E/Z)- 10 . - On treatment with BF₃O(C₂H₅)₂ (E)- 2 isomerizes by cleavage of the C(δ), O-bond to the γ-ketoester (E)- 20 (s. Scheme 2). Conversion of (Z)- 2 with FeCl₃ gives the isomeric furan compound 21 exclusively.     

Fullerene-Acetylene Molecular Scaffolding: Chemistry of 2-functionalized 1-ethynylated C60, oxidative homocoupling,hexakis-adduct formation,and attempted synthesis of C

On the way to the fullerene-acetylene hybrid carbon allotropes 2 and 6 , the oxidative homocoupling of the 2-functionalized 1-ethynylated C₆₀ derivatives 11, 12, 14 , and 15 was investigated. Under Glaser-Hay conditions, the two soluble dumbbell-shaped bisfullerenes 17 and 18 , with two C₆₀ moieties linked by a buta-1,3-diynediyl bridge, were formed in 52 and 82% yield, respectively (Scheme 2). Cyclic-voltammetric measurements revealed that there is no significant electronic communication between the two fullerene spheres via the buta-1,3-diynediyl linker. Removal of the 3,4,5,6-tetrahydro-2H-pyran-2-yl (Thp) protecting groups in 18 gave in 80% yield the highly insoluble dumbbell 19 with methanol groups in the 2,2′-positions of the buta-1,3-diynediyl-bridged carbon spheres. Attempted conversion of 19 to the all-carbon dianion 6 (C) via base-induced elimination of formaldehyde was not successful presumably due to exo-dig cyclization of the formed alkoxides. The occurrence of this cyclization under furan formation was proven for 2-[4-(trimethylsilyl)buta-1,3-diyn-1-yl][60]fullerene-1-methanol ( 21 ), a soluble model compound for 19 (Scheme 3). To compare the properties of ethynylated fullerene mono-adducts to those of corresponding higher adducts, hexakis-adducts 26 and 28 with an octahedral functionalization pattern resulting from all-e (equatorial) additions were prepared by the reversible-template method of Hirsch (Scheme 4). Reaction of the ethynylated mono-adducts 25 or 13 with diethyl 2-bromomalonate/1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in the presence of 1,9-dimethylanthracene (DMA) as reversible template led to 26 and 28 in 28 and 22% yield, respectively. Preliminary experiments indicated a significant change in reactivity and NMR spectral properties of the fullerene addends with increasing degree of functionalization.     

RuO4-catalyzed oxidative polycyclization of the Cs-symmetric isoprenoid polyene digeranyl. An unexpected stereochemical outcome

The RuO₄-catalyzed oxidative polycyclization of digeranyl, a C_s-symmetric tetraene possessing a repetitive 1,5-diene structural motif, has been studied. The required substrate has been synthesized by Ti(III)-mediated tail-to-tail homocoupling of geranyl bromide. The process afforded two hitherto unknown isomeric tris-tetrahydrofuran products possessing unexpected all-threo cis-trans-cis and cis-trans-trans relative configuration. The new stereochemical outcome is explained based on previously formulated chelation or steric control models on the basis of structural differences between digeranyl and previously studied isoprenoid polyenes farnesyl acetate, geranylgeranyl acetate and squalene.     

Cyclotrimerization of Benzobarrelene: Synthesis of New Isomeric Barrelene Architectures

The cyclotrimerization reaction of benzobarrelene derivatives was investigated. Dibromobenzobarrelene 10 was converted to the bromostannyl derivative 11 , which was used as the substrate of the cyclotrimerization reaction. Thus, reaction of 11 , with copper(I) thiophene‐2‐carboxylate (CuTC) gave a mixture of the isomeric cyclotrimers 5 and 6 and the dimers 12 and 13 , in addition to a trace of protodestannylated bromoalkene 14 (Scheme 2).     

C2-Symmetric Bicyclic Diols as Chiral Ligands in the titanate-catalyzed enantioselective addition of alkylzinc reagents to aldehydes

Enantiomerically pure C₂-symmetric 1,4-diols embodying bicyclic C-frameworks were synthesized by means of asymmetric carbo-Diels-Alder reactions as key steps (Scheme 1). They were investigated as chiral ligands in the enantioselective addition of ZnEt₂ to aromatic aldehydes. In the presence of 20–40 mol-% of the titanates formed from these diols and [Ti(i-PrO)₄] at ?78°, the respective 1-arylpropanols were obtained with enantiomer ratios up to 93:7 (Scheme 2, Table).     

Synthesis of a Phosphonic Acid Analogue of N-Acetyl-2,3-didehydro-2-deoxyneuraminic Acid,an Inhibitor of Vibrio cholerae Sialidase

The synthesis of the phospha analogue 10 of DANA ( 2 ) is described. Bromo-hydroxylation of the known 11 (→ 12 and 13 ) followed by treatment of the major bromohydrin 13 with 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) gave the oxirane 14 (Scheme 1). Depending on the solvent, TiBr₄ transformed 14 into 16 or into a 15 / 16 mixture. Reductive debromination of 16 (→ 17 ), followed by benzylation provided 18 . Oxidattve decarboxylation (Pb(OAc)₄) of the acid, obtained by saponification of 18 , yielded the anomeric acetates 19 and 20 . While 19 was inert under the conditions of phosphonoylation, the more reactive imidate 22 , obtained together with 23 from 19 / 20 via 21 (Scheme 2), gave a mixture of the phosphonates 24 / 25 and the bicyclic acetal 26 . Debenzylation of 24 / 25 and acetylation led to the acetoxyphosphonates 27 / 28 . Since β-elimination of AcOH from 27 / 28 proved difficult, the bromide 34 was prepared from 27 / 28 by photobromination and subjected to reductive elimination with Zn/Cu (→ 35 ; Scheme 3). This two-step sequence was first investigated using the model compounds 30 and 31 . Transesterification of 35 , followed by deacetylation gave 10 , which is a strong inhibitor of the Vibrio Cholerae sialidase.     

Synthese von Triafulven-Vorstufen für Retro-Diels-Alder-Reaktionen

Synthesis of Triafulvene Precursors for Retro-Diels-Alder Reactions Triafulvene precursors exo? 15 and endo? 15 have been prepared by addition of dibromocarbene to benzobarrelene 12 followed by a lithium-halogen exchange, methylation, and elimination of HBr ( 12→13→14→15 ), (Scheme 2). Gas-phase pyrolysis of exo/endo-mixtures of 15 above 400° gave minor amounts of naphthalene ( 16 ), traces of a hydrocarbon C₄H₄ identified by MS (presumably triafulvene 1 ) and predominantly (36%) the isomerization product 17 (Scheme 3). In a second synthetic approach the well-known cycloheptatriene-norcaradiene equilibrium of type 26?27 has been utilised to prepare various endo-trans-3-(X-methyl) tricyclo[3.2.2.0^2,4]nona-6,8-dienes 31 (Scheme 5). However, numerous elimination experiments 31→9 failed so far. The structure of two rearrangement products 33 and 34 (Scheme 6) has been elucidated.     

Ring expansion and <Emphasis Type="Italic">N</Emphasis>,<Emphasis Type="Italic">N</Emphasis>-dimethylformamide-solvation of the cyclodimeric complex bis(3-pyridyl)dimethylsilanedicholoropalladium(II)

The reaction of (COD)PdCl₂ (COD = 1,5-cyclooctadiene) with (3-Py)₂SiMe₂ (bis(3-pyridyl)dimethylsilane) in acetone produces single crystals consisting of cyclodimers, [PdCl₂((3-Py)₂SiMe₂)]₂, whereas the similar reaction in a mixture of dichloromethane and ethanol yields amorphous submicrospheres consisting of cyclotrimers, [PdCl₂((3-Py)₂SiMe₂)]₃. In a boiling chloroform solution, the cyclodimers are completely converted to the cyclotrimers. The structures of both cyclic species are locked at temperatures below 0 °C. The cyclotrimer equilibrates to the cyclodimer, the cyclotrimer, and cyclotrimeric mono-DMF adduct, [Pd₃Cl₅(DMF)((3-Py)₂SiMe₂)₃]Cl in the mole ratio of 6:1:5 in DMF solution at room temperature. The cyclodimer finally reaches the equilibrium in the same condition. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Synthesis and Reactions of Optically Active 1,3-Diols

The ‘syn’-1,3-diols 3 , 4 and 5 with a C₇, C₆, and C₅ chain, respectively, were synthesized from methyl hydrogen 3-hydroxyglutarate ( 2 ; Schemes 1 and 2). The latter is available in (R)- and (S)-configuration. Octyl (3R)-4-chloro-3-hydroxybutanoate ( 17 ) is an alternative starting material for the preparation of 5 (Scheme 3.) The epoxide 20 , derived from 5 in a one-pot reaction, is a versatile synthon, which selectively reacts with a great number of nucleophiles (Scheme 4).     

Selenacalix[4]dithienothiophene: Synthesis,Structure, and Complexation of a Cyclic Tetramer of Selenide‐Bridging Dithienothiophene

An efficient cyclization toward a cyclic tetramer of dithienothiophene (DTT) linked by divalent selenium atoms has been developed via palladium‐catalyzed coupling reaction of (nBu₃Sn)₂Se. X‐ray analysis revealed its highly symmetrical structure had an alternate arrangement of DTT units. There are several Se???π interactions forming a supramolecular network leading to large void channel space. The cyclic tetramer possesses moderate electron‐donating ability. Furthermore, the cyclic tetramer undergoes complexation with C₆₀ in a 1:2 ratio in the solid state to give a highly symmetrical three‐dimensional array of C₆₀.     

Multiple Adducts of C60 by Tether-Directed Remote Functionalization and synthesis of soluble derivatives of new carbon allotropes Cn(60+5)

A comprehensive series of multiple adducts of C₆₀ was prepared by tether-directed remote functionalization. When the tether-reactive-group conjugates 2 and 10 were attached to methano[60]fullerenecarboxylic acid ( = cyclopropafullerene-C₆₀-I_h-carboxylic acid) and C₆₀, respectively, the e-bis-adducts 4 and 9 (Schemes 1 and 2) were obtained with complete regioselectivity as predicted by semi-empirical PM3 calculations (Fig. 2). Attachment of the anchor-tether-reactive-group conjugate 13 to C₆₀ by Bingel reaction, followed by double intramolecular Diels-Alder cycloaddition afforded the tris-adduct 12 (Scheme 3). Starting from 12 , a series of selective e-additions led to the tetrakis-adducts 16 and 19 (Scheme 4), pentakis-adducts 20 – 23 (Scheme 5), and, ultimately, to hexakis-adducts 24 and 25 (Scheme 6), and 29 and 30 (Scheme 7) with a pseudo-octahedral addition pattern on the fullerene core. Oxidative cyclization of diethynylmethanofullerene 30 under Eglinton-Glaser conditions afforded the trimeric and tetrameric acetylenic macrocycles 26 , with three, and 27 , with four appended C₆₀ moieties, respectively (Scheme 8). These multinanometer-sized compounds are the first soluble derivatives of C₁₉₅ and C₂₆₀, two members of a new class of fullerene-acetylene hybrid C-allotropes with the general formula C_{n(60 + 5)}. The matrix-assisted laser-desorption time-of-flight mass spectra of 26 and 27 showed a remarkable fragmentation; the sequential loss of fullerene spheres led to the formation of ions corresponding to mono-fullerene adducts of the cyclocarbons cyclo-C₁₅ and cyclo-C₂₀ (Fig. 4). Large solvent effects were observed in the Bingel addition of 2-bromomalonates to higher adducts of C₆₀, with the use of polar solvents enhancing the reaction rate without loss of regioselectivity. Experimental evidence for the enhanced reactivity of e_face over e_edge bonds was obtained, which had previously been predicted in computational studies. The correlated series of mono- to hexakis-adducts of C₆₀ allowed identification of the changes in reactivity and physical properties that occur, when the conjugated π-electron chromophore of the fullerene is reduced as a result of increasing functionalization; this analysis is the subject of the directly following paper.     

Synthesis of Novel Chiral C2-Symmetric Bisoxazoline Ligands Containing 2,5-Di( m -substituted)phenyl-1,3,4-oxadiazole

Abstract

Seven novel chiral C₂-symmetric substituted bisoxazoline ligands containing 2,5-di(m-substituted)phenyl-1,3,4-oxadiazole have been synthesized from 2,5-di-(m-carboxylphenyl)-1,3,4-oxadiazole and aminoalcohol by NaOH or Et₃N cyclization method via halogenated amide intermediate.     

Synthesis of Unique Ceramides and Cerebrosides Occurring in Human Epidermis

The sphingolipids 1a , b and 2a , b which play important roles in epidermal barrier function, were synthesized by N-acylation of C₁₈-sphingosine 3 and 1-O-glucosylated C₁₈-sphingosine 6 , respectively, with ω-acyloxy-substituted fatty acids 4 and 5 (Scheme 1). These fatty acids were obtained from ω-hydroxy-substituted fatty acids 8 and 9 by esterification with linoleic acid ( 7 ). The C₃₄-fatty acid 8 was prepared as follows: C₂₅-Compound 18 was obtained by means of a Wittig reaction of C₁₃-aldehyde 13 with C₁₂-phosphonium salt 15 or of C₁₂-aldehyde 24 with C₁₃-phosphonium salt 21 , respectively, and subseqent hydrogenation and O-deprotection (Scheme 2). Alternatively, 8 was prepared via 30 by copper-catalyzed coupling of C₁₃-alkyl halide 19 with the Grignard reagent derived from C₁₂-alkyl bromide 14 (Scheme 2). Oxidation of 18 to aldehyde 39 and Wittig reaction with C₉-phosphonium salt 41 furnished the desired ω-hydroxy-substituted fatty acid 8 , after O-deprotection (Scheme 3). Similarly, Wittig reaction of C₁₁-phosphonium salt 22 with C₁₂-aldehyde 24 furnished C₂₃-aldehyde 40 , after hydrogenation, O-deprotection, and oxidation; Wittig reaction with compound 41 and subsequent deprotection afforded the desired C₃₂-fatty and 9 (Scheme 3). an alternative strategy furnished compound 8 by a coupling reaction of alkyne 53 with ω-bromo-substitued fatty acid 52 , obtained from compounds 24 and 47 by Wittig reaction, hydrogenation, and introduction of bromide (Scheme 4). Hydrogenation (Lindlar's catalyst) of the resulting C₃₄-alkyne 54 and deprotection furnished 8 .     

Massenspektrometrische Identifizierung und Synthese isomerer und homologer Spermidin- und Spermin-Derivate. 25. Mitteilung über das massenspektrometrische Verhalten von Stickstoffverbindungen. 161. Mitteilung über Alkaloide

Synthesis of isomeric and homologous spermidine and spermine derivatives and their identification by mass spectrometry. The structure of homologous and isomeric spermidines and spermines follows from mass-spectroscopical analysis of their peracetyl (see text, footnote 3) (Table 1) or tosyl-acetyl (Table 2) derivatives. In the case of the peracetyl compounds, triads of peaks are recorded which, according to the number of methylene groups between the nitrogen atoms, show mass numbers characteristic for each of the substances (Scheme 1, ions b , d , e and c ). On the basis of cyclic ions of type f (Scheme 2), occurring in the mass spectra of N-acetyl derivatives, tosylated on a secondary amino nitrogen atom, deductions can be drawn as to the number of methylene groups between neighbouring tosylated and acetylated nitrogen atoms in these compounds.