A Novel Imidazole Nucleoside Containing a Diaminodihydro-S-triazine as a Substituent: Inhibitory Activity Against the West Nile Virus NTPase/Helicase

The attempted synthesis of a ring-expanded guanosine (1) containing the imidazo[4,5-e][1,3]diazepine ring system by condensation of 1-(2′-deoxy-β-D-erythropentofuranosyl)-4-ethoxycarbonylimidazole-5-carbaldehyde (2) with guanidine resulted in the formation of an unexpected product, 1-(2′-deoxy-β-D-erythropentofuranosyl)-5-(2,4-diamino-3,6-dihydro-1,3,5-triazin-6-yl)imidazole-4-carboxamide (7). The structure as well as the pathway of formation of 7 was corroborated by isolation of the intermediate, followed by its conversion to the product. Nucleoside 7 showed promising in vitro anti-helicase activity against the West Nile virus NTPase/ helicase with an IC ₅₀ of 3-10 μg/mL.     

The SO4(.-)-induced chain reaction of 1,3-dimethyluracil with peroxodisulphate

The sulphate radical SO4(.-) reacts with 1,3-dimethyluracil (1,3-DMU) (k = 5 X 10(9) dm3 mol-1 s-1) thereby forming with greater than or equal to 90 per cent yield the 1,3-DMU C(5)-OH adduct radical 4 as evidenced by its absorption spectrum and its reactivity toward tetranitromethane. Pulse-conductometric experiments have shown that a 1,3-DMU-SO4(.-) aduct 3 as well as the 1,3-DMU radical cation 1, if formed, must be very short-lived (t1/2 less than or equal to 1 microsecond). The 1,3-DMU C(5)-OH adduct 4 reacts slowly with peroxodisulphate (k = 2.1 X 10(5) dm3 mol-1 s-1). It is suggested that the observed new species is the 1,3-DMU-5-OH-6-SO4(.-) radical 7. At low dose rates a chain reaction is observed. The product of this chain reaction is the cis-5,6-dihydro-5,6-dihydroxy-1,3-dimethyluracil 2. At a dose rate of 2.8 X 10(-3) Gys-1 a G value of approximately 200 was observed ([1,3-DMU] = 5 X 10(-3) mol dm-3; [S2O8(2-)] = 10(-2) mol dm-3; [t-butanol] = 10(-2) mol dm-3). The peculiarities of this chain reaction (strong effect of [1,3-DMU], smaller effect of [S2O(2-)8]) is explained by 7 being an important chain carrier. It is proposed that 7 reacts with 1,3-DMU by electron transfer, albeit more slowly (k approximately 1.2 X 10(4) dm3 mol-1 s-1) than does SO4(.-). The resulting sulphate 6 is considered to hydrolyse into 2 and sulphuric acid which is formed in amounts equivalent to those of 2. Computer simulations provide support for the proposed mechanism. The results of some SCF calculations on the electron distribution in the radical cations derived from uracil and 1-methyluracil are also presented.     

Transition metal complexes IX. Nickel complexes with a chiral azaphosphole ligand

The reaction of (−)-(R)-myrtenal and (+)-(R)-phenylethylamine gave a Schiff base 1 which was reacted with MePBr₂ in the presence of a base to give under dehydrohalogenation of an intermediate McCormack product a salt 2. Treatment of 2 with sodium led to the formation of the azaphosphole 4. η³-C₃H₅NiCl and 4 gave a 1:1 adduct 5 and nickel(0) gave a 1:4 complex 6. Compounds 4–6 were characterized by NMR spectroscopy as well as by single crystal X-ray structure determination.     

Identification and characterization of a novel linkage isomerization in the reaction of trans-diamminedichloroplatinum(II) with 5'-d(TCTACGCGTTCT)

The oligonucleotide 5'-d(TCTACGCGTTCT) reacts with trans-diamminedichloroplatinum(II) to yield primarily trans-[Pt(NH3)2[d(TCTACGCGTTCT)-N7-G(6),N7-G(8)]], containing the desired trans-[Pt(NH3)2[d(GCG)]] 1,3-cross-link. A key element of the platination reaction is the use of low pH to suppress coordination at A(4). The product was fully characterized by pH-dependent NMR titrations, enzymatic degradation analysis, and 195Pt NMR spectroscopy. Interestingly, the 1,3-cross-linked adduct is unstable at neutral pH, rearranging unexpectedly to form the linkage isomer trans-[Pt(NH3)2[d-(TCTACGCGTTCT)-N3-C(5),N7-G(8)]]. This rearrangement product is more stable than the initially formed isomer and could be characterized by pH-dependent NMR titrations, enzymatic degradation analysis, liquid secondary ion mass spectrometric analysis of an enzymatically digested fragment, 195Pt NMR spectroscopy, and modified Maxam-Gilbert footprinting experiments. By contrast, the 1,3-intrastrand cross-linked isomer rearranges during the course of both pH titration and enzymatic degradation experiments to form the 1,4-adduct. The equilibrium constant for this rearrangement is approximately 3, favoring the 1,4-adduct. Kinetic studies of the linkage isomerization reaction reveal t1/2 values for the first-order disappearance of the 1,3-intrastrand cross-linked isomer ranging from 129 (at 30 degrees C) to 3.6 h (at 62 degrees C), with activation parameters delta H not equal to = 91 +/- 2 kJ/mol and delta S not equal to = -58 +/- 8 J/(mol.K). Mechanistic implications of these kinetic results as well as the general relevance of this linkage isomerization reaction to platinum-DNA chemistry are briefly discussed.     

X-ray and deuterium labeling studies on the abnormal ring cleavages of a 5 beta-epoxide precursor of formestane

A new convergent synthesis of the antitumor steroid formestane (4-OHA) 5 has been performed from the easily available epimeric mixture of 5 alpha- and 5 beta-androst-3-en-17-one 1a and 1b in order to attempt a yield improvement. A two-step oxidative route followed by base-catalyzed isomerization was applied to the 5 alpha- and 5 beta-epimers 1a and 1b, either as a mixture or separately, leading to the title compound 5. From epimer 1a an efficient process was attained to prepare the desired aromatase inhibitor formestane. Epimer 1b led to the formation of the same compound 5. Additionally, 1b have also been converted in 5 beta-hydroxyandrostane-3,17-dione 12 and androst-4-ene-3,17-dione 13, revealing an unexpected reactivity of the 3 beta,4 beta-epoxy-5 beta-androstan-17-one intermediate 6 formed from 1b during the first oxidative step with performic acid. Cleavage of the epoxide 6 led to the trans-diaxial and the trans-diequatorial vic-diols 7 and 8 and to the 1,3-diol 9. The formation of the abnormal products 8 and 9 were investigated through X-ray and deuterium labeling studies. Diol 8 was formed through a trans-diequatorial epoxide ring opening and the 1,3-diol 9 was formed through an intramolecular rearrangement involving a 1,2-hydride shift. All the vic-diols 3, 7 and 8 formed, proved to be good precursors for the synthesis of the target compound 5.     

Synthetic studies towards a new scaffold, spirobicycloimidazoline

A new scaffold consisting of a carbocycle and a substituted imidazoline in an orthogonal arrangement was synthesized as a potential specific inhibitor of glycosidases. The spirobicycloimidazoline, (5R,6R,7R,8R)-8-(hydroxymethyl)-2-phenyl-1,3-diazaspiro[4.4]non-1-ene-6,7-diol, was synthesized from methyl 2-O-p-methoxybenzyl-3,4-di-O-benzyl-alpha/beta-D-gluco-6-enopyranoside via (1R,2S,3S,4R,5S)-3,4-bis(benzyloxy)-2-(4-methoxybenzyloxy)-5-vinyl-cyclopentanol. The ring contraction of the 6-enopyranoside in the presence of zirconocene equivalent ('Cp(2)Zr') reagent gave exclusively the corresponding cyclopentanol without cleavage of the PMB protecting group. In the course of the study, a new alpha-mannosidase inhibitor, (1R,2R,3R,5R)-5-amino-3-hydroxymethyl-cyclopentane-1,2-diol, was also discovered.     

Synthesis and antibacterial activity of egonol derivatives

Synthesis of egonol derivatives, 5-(3'-chloropropyl)-7-methoxy-2-(3',4'-methylenedioxyphenyl)benzofuran 1, 5-(3'-bromopropyl)-7-methoxy-2-(3',4'-methylenedioxyphenyl)benzofuran 2, 3-[2-(1,3-benzodioxol-5-yl)-7-methoxy-1-benzofuran-5-yl]propanal 3, 5-(3'-iodopropyl)-7-methoxy-2-(3',4'-methylenedioxyphenyl)benzofuran 4, 5-[3-(3'-bromopropyloxy) propyl]-7-methoxy-2-(3',4'-methylenedioxyphenyl)benzofuran 5, 3-[2-(1,3-benzodioxol-5-yl)-7-methoxy-1-benzofuran-5-yl]propylmethanoate 6, 3-[2-(1,3-benzodioxol-5-yl)-7-methoxy-1-benzofuran-5-yl]propyloleate 7, 5-[3'-hydroxypropyl]-6-bromo-7-methoxy-2-(3',4'-methylenedioxyphenyl)benzofuran 8, 4-[2-(1,3-benzodioxol-5-yl)-7-methoxy-1-benzofuran-5-yl]butanenitrile 9, 3-[2-(1,3-benzodioxol-5-yl)-7-methoxy-1-benzofuran-5-yl]propylbenzoate 10, 5-[3'-hydroxypropyl]-7-methoxy-3-nitro-2-(3',4'-methylenedioxyphenyl)benzofuran 11 and their antibacterial activity against Staphylococcus aureus, Bacillus subtilis, Candida albicans and Escherichia coli are reported. The starting material egonol 5-[3'-(hydroxy)propyl]-7-methoxy-2-(3', 4'methylenedioxyphenyl)benzofuran was isolated from seeds of Styrax officinalis L. The structural elucidication of these compounds (1-11) was established using 1D ((1)H, (13)C), 2D NMR (HMBC, HMQC, COSY) and LCMS spectroscopic data. While egonol and some synthesised new compounds show similar antibacterial activity and MIC values against S. aureus, B. subtilis, C. albicans and E. coli, other new derivatives show different activity against S. aureus, B. subtilis, C. albicans and E. coli.     

Formation of a New Biogenic Aldehyde Adduct by Incubation of Tryptamine with Rat Brain Tissue

Tryptamine was degraded by incubation with rat brain homogenate to an unknown product. The reaction was stimulated by the nonionic detergents Triton X-100 and Lubrol PX and less by the zwitterionic detergent 3-[(3-cholamidopropyl)dimethylammonio]1-propanesulfonate (CHAPS). The same results were obtained with pig brain and bovine brain. The monoamine oxidase inhibitor pargyline inhibited the reaction strongly, indicating the participation of the enzyme on the reaction. Addition of 17,000 g supernatant from rat brain homogenate increased the formation effectively whereas phospholipids or chloroform/methanol (7:3) extract from the 17,000 g supernatant showed only little or no effect. Chromatographic and electrophoretic properties as well as the chemical reaction of the product with specific reagents suggest that the compound consists of an indole part and an amino acid part. The product could be identified by fast atom bombardment mass spectrometry and by comparison with the synthetic substance (4R)-2-(3-indolylmethyl)-1,3-thiazolidine-4-carboxylic acid. It is formed by the enzymatic oxidation of tryptamine producing indole-3-acetaldehyde which spontaneously cyclizes with free L-cysteine from the tissue. The results suggest that the reaction of biogenic aldehydes with brain macromolecules may proceed via an analogous reaction.     

Induction of lacI mutations in Big Blue Rat-2 cells treated with 1-(2-hydroxyethyl)-1-nitrosourea: a model system for the analysis of mutagenic potential of the hydroxyethyl adducts produced by 1,3-bis (2-chloroethyl)-1-nitrosourea.

We have investigated the genotoxic effects of 1-(2-hydroxyethyl)-1-nitrosourea (HENU). We have chosen this agent because of its demonstrated ability to produce N7-(2-hydroxyethyl) guanine (N7-HOEtG) and O⁶-(2-hydroxyethyl) 2′-deoxyguanosine (O⁶-HOEtdG); two of the DNA alkylation products produced by 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU). For these studies, we have used the Big Blue Rat-2 cell line that contains a lambda/lacI shuttle vector. Treatment of these cells with HENU produced a dose dependent increase in the levels of N7-HOEtG and O⁶-HOEtdG as quantified by HPLC with electrochemical detection. Treatment of Big Blue Rat-2 cells with either 0, 1 or 5 mM HENU resulted in mutation frequencies of 7.2±2.2×10⁻⁵, 45.2±2.9×10⁻⁵ and 120.3±24.4×10⁻⁵, respectively. Comparison of the mutation frequencies demonstrates that 1 and 5 mM HENU treatments have increased the mutation frequency by 6- and 16-fold, respectively. This increase in mutation frequency was statistically significant (P<0.001). Sequence analysis of HENU-induced mutations have revealed primarily G:C→A:T transitions (52%) and a significant number of A:T→T:A transversions (16%). We propose that the observed G:C→A:T transitions are produced by the DNA alkylation product O⁶-HOEtdG. These results suggest that the formation of O⁶-HOEtdG by BCNU treatment contributes to its observed mutagenic properties.     

Synthesis of AZT analogues: 7-(3-azido-2-hydroxypropyl)-, 7-(3-amino-2-hydroxypropyl)-,7-(3-triazolyl-2-hydroxypropyl)theophylline

Nucleophilic displacement of the tosyloxy group in 7-(2-hydroxy-3-p-toluenesulfonyloxypropyl)theophylline (1) with azide anion afforded 7-(3-azido-2-hydroxypropyl)theophylline (2). Reduction of the 3-azido group in 2 with Ph3P/Py/NH4OH afforded the 3-amino derivative 4, alternatively obtained by regioselective amination of 7-(2,3-epoxypropyl)theophylline (3). Selective acetylation of 4 gave the N-acetyl derivative 5. 1,3-Dipolar cycloaddition of the azide group in 2 with N1-propargyl thymine (6) afforded the regioisomeric triazole 7.     

Synthesis of 2-bromomethyl-3-hydroxy-2-hydroxymethyl-propyl pyrimidine and theophylline nucleosides under microwave irradiation. Evaluation of their activity against hepatitis B virus

Alkylation of 2-methylthiopyrimidin-4(1H)-one (1a) and its 5(6)-alkyl derivatives 1b-d as well as theophylline (7) with 2,2-bis(bromomethyl)-1,3-diacetoxypropane (2) under microwave irradiation gave the corresponding acyclonucleosides 1-[(3-acetoxy-2-acetoxymethyl-2-bromomethyl)prop-1-yl]-2-methyl-thio pyrmidin-4(1H)-ones 3a-d and 7-[(3-acetoxy-2-acetoxymethyl-2-bromomethyl)prop-1-yl]theophylline (8), which upon further irradiation gave the double-headed acyclonucleosides 1,1 '-[(2,2-diacetoxymethyl)-1,3-propylidene]-bis[(2-(methylthio)-pyrimidin-4(1H)-ones] 4a-c, and 7,7 '-[(2,2-diacetoxymethyl)-1,3-propylidene]-bis(theophylline) (9). The deacetylated derivatives were obtained by the action of sodium methoxide. The activity of deacetylated nucleosides against Hepatitis B virus was evaluated. Compound 5b showed moderate inhibition activity against HBV with mild cytotoxicity.     

π-Arene complexes.: Part 12. Synthesis of chromiumtricarbonyl complexes of quinoline and N-methylindoles and selected metallation reactions

The lithiation of indole, using a slight excess of n-butyl lithium in THF, followed by methylation and reaction with [Cr(CO)₆] in refluxing dibutyl ether, resulted in the formation of [Cr(η⁶-N-methylindole)(CO)₃] (1a) and [Cr(η⁶-N-methyl-2-methylindole)(CO)₃] (1b). In contrast, lithiation of quinoline in THF, silylation and the subsequent reaction with [Cr(CO)₆] under similar reaction conditions, afforded [Cr(η⁶-N-trimethylsilyl-2-butyl-1,2-dihydroquinoline)(CO)₃] (2) and [Cr(η⁶-{2-butyl-1,2,3,4-tetrahydroquinoline})(CO)₃] (3). The formation of [Cr(η⁶-2,2′-bis{N-methylindolyl})(CO)₃] (4) implied lithiation at the 2-position of 1a. However, metallation at the 7-position was also indicated during the same reaction. In the presence of [Mn(CO)₅Br], product 4 and the transmetallation product [Cr(η⁶-{7-(N-methylindolyl)Mn(CO)₅})(CO)₃] (5) were isolated. Reaction with titanocene dichloride gave [Cr(η⁶-{2-(N-methylindolyl)TiCp₂Cl})(CO)₃] (6), which slowly converted into [TiCp₂{Cr(η⁶-2-(N-methylindolyl)(CO)₃}₂] (7).     

New method for the preparation of 3'- and 2'-O-phosphoramidites of 2'- and 3'-difluoromethyluridine derivatives

Hydrogenation of 2'-deoxy-2'-difluoromethylene-5'-O-dimethoxytrityluridine (1) and 3'-deoxy-3'-difluoromethylene-5'-O-dimethoxytrityluridine (7), gave the corresponding 2'- and 3'-difluoromethyluridine derivatives 2a and 8a. Detritylation of compounds 2a, 2b and 8a, 8b resulted in the formation of 1-(2-deoxy-2-C-difluoromethyl-beta-D-arabino-pentofuranosyl)uracil (3a) and 1-(3-deoxy-3-C-difluoromethyl-beta-D-xylo-pento furanosyl)- uracil (9a) as well as corresponding minor isomers 3b and 9b. Compounds 3a and 3b were also obtained from 2'-deoxy-2'-difluoromethylene-3',5'-O-(tetraisopropyldisiloxane-1,3-diyl)uridine (4). Finally, phosphitylation of 2a and 8a provided the title 2'- and 3'-O-phosphoramidites 6 and 10.     

Formation of Thiazolidine-4-Carboxylic Acid Represents a Main Metabolic Pathway of 5-Hydroxytryptamine in Rat Brain

Incubation of 5-hydroxytryptamine (5-HT) with rat brain homogenate resulted in the formation of (4R)-2-[3'-(5'-hydroxyindolyl)-methyl]-1,3-thiazolidine-4-carboxyl ic acid (5'-HITCA) as the major metabolite. The substance represents the condensation product of 5-hydroxyindole-3-acetaldehyde with L-cysteine. The chemical structure was confirmed by chromatographic and chemical methods as well as by fast atom bombardment mass spectrometry. Incubation of 5-HT in the presence of L-cysteine yielded the thiazolidine as the main metabolite up to 4 h. Under these conditions, the concentration of 5-hydroxyindole-3-acetic acid (5-HIAA) amounted to about 20% and 57% of 5'-HITCA (0.5 h and 4 h, respectively). In contrast to these findings, indole-3-acetic acid (IAA) was identified as the major metabolite when tryptamine was incubated under similar conditions. (4R)-2-(3'-Indolylmethyl)-1,3-thiazolidine-4-carboxylic acid (ITCA) was found to be the main conversion product of tryptamine only during the first 30 min. To investigate the fate of the thiazolidines, radiolabelled and unlabelled ITCA was incubated with rat brain homogenate. The compound was degraded enzymatically and rapidly. Subcellular fractionation revealed that the enzyme activity was present mainly in the cytosolic fraction whereas the preparation of mitochondria showed less activity. The responsible enzyme is presumably a carbon-sulfur lyase (EC 4.4.1.-). The major metabolite was isolated by HPLC and identified by mass spectrometry as well as by comparison with reference compounds to be IAA.(ABSTRACT TRUNCATED AT 250 WORDS)     

Genotoxicity of 1,3- and 1,6-dinitropyrene: induction of micronuclei in a panel of mammalian test cell lines

1,3-Dinitropyrene (1,3-DNP) and 1,6-dinitropyrene (1,6-DNP) were assessed for their potential to increase the frequencies of micronuclei in a panel of test cell lines consisting of H4IIEC3/G, 5L, 5L/r-1,3-DNP1, 208F, V79, V79/r-1,6-DNP1, HepG2 and BWI-J cells, which have been partially characterized for their expression of xenobiotic metabolising enzymes. The micronuclei were analyzed for the presence or absence of kinetochores indicating the occurrence of aneuploidy or chromosome breakage, respectively. 1,3-DNP caused a substantial increase in the frequency of micronuclei only in V79 cells. 1,6-DNP was strongly genotoxic in lines H4IIEC3/G⁻, 208F, V79 and, to a minor degree, in 5L/r-1,3-DNP1. It caused the formation of kinetochore-positive as well as kinetochore-negative micronuclei in V79 cells but only of kinetochore-negative micronuclei in H4IIEC3/G⁻ and 208F cells. 1,6-DNP-induced formation of micronuclei was paralleled by the appearance of multinucleated cells. Treatment of V79 cells with 1,3-DNP resulted in the same types of damage as treatment with 1,6-DNP, although considerably higher concentrations were required.The results show that 1,6-DNP can be highly genotoxic in mammalian cells, whereas, at least in the panel of test cell lines used, 1,3-DNP possesses only a low genotoxic activity. 1,3-DNP appears to be activated to genotoxic products in V79 cells by the same pathway(s) as 1,6-DNP.     

Synthesis of 3-aminoimidazo[4,5-c]pyrazole nucleoside via the N-N bond formation strategy as a [5:5] fused analog of adenosine

3-Amino-6-(beta-D-ribofuranosyl)imidazo[4,5-c]pyrazole (2) was synthesized via an N-N bond formation strategy by a mononuclear heterocyclic rearrangement (MHR). A series of 5-amino-1-(5-O-tert-butyldimethylsilysilyl-2,3-O-isopropylidene-beta-D-ribofuranosyl)-4-(1,2,4-oxadiazol-3-yl)imidazoles (6a-d), with different substituents at the 5-position of the 1,2,4-oxadiazole, were synthesized from 5-amino-1-(beta-D-ribofuranosyl)imidazole-4-carboxamide (AICA Ribose, 3). It was found that 5-amino-1-(5-O-tert-butyldimethylsilyl-2,3-O-isopropylidene-beta-D-ribofuranosyl)-4-(5-methyl-1,2,4-oxadiazol-3-yl)imidazole (6a) underwent the MHR with sodium hydride in DMF or DMSO to afford the corresponding 3-acetamidoimidazo[4,5-c]pyrazole nucleoside(s) (7b and/or 7a) in good yields. A direct removal of the acetyl group from 3-acetamidoimidazo[4,5-c]pyrazoles under numerous conditions was unsuccessful. Subsequent protecting group manipulations afforded the desired 3-amino-6-(beta-D-ribofuranosyl)imidazo[4,5-c]pyrazole (2) as a 5:5 fused analog of adenosine (1).     

Dehydroxylation of a 7 beta-hydroxy-C27 plant sterol in rat liver

(22R)-Cholest-5-ene-3 beta,7 alpha,22-triol and the isomeric (22R)-cholest-5-ene-3 beta,7 beta,2-triol were 7-dehydroxylated by rat liver microsomes, after addition of NAD+ to the incubations. The product from both sterols was identified as (22R)-22-hydroxycholesta-4,6-dien-3-one by gas chromatography-mass spectrometry. The overall conversion of the 7 alpha-compound had an apparent Vmax of 5 nmol/mg protein per h, about 3-times higher than that of the 7 beta-isomer. Km was about 0.018 mmol/l in both reactions. NAD+ was required for the 7-dehydroxylation to proceed, conceivably by serving as cofactor in formation of the intermediate 7 beta,2-dihydroxy-4-cholesten-3-one. EDTA had a stimulatory effect upon the product formation. 7 alpha-Dehydroxylation of the bile acid precursor 7 alpha-hydroxy-4-cholesten-3-one has been demonstrated in liver tissue, but a 7 beta-hydroxy-C27-steroid dehydroxylating enzyme has previously not been identified. The results are discussed in relation to the marked differences in effect on neoplastic growth by the two isomeric hydroxysterols.     

Asymmetric catalysis 87. Enantioselective allylation of 1,5-dimethylbarbituric acid with Pd catalysts and new optically active PN ligands

The new PN ligands 5, 6 and 7 were prepared by Schiff base condensation of 2-formylphenyl(diphenyl)phosphine (1) with the optically active amines (R)-(−)-2-aminobutanol (2), (S)-(+)-2-aminobutanol (3) and (1S,2S)-2-amino- 1-phenyl-1,3-propanediol (4). These new ligands were used in the Pd catalysed allylation of 1,5-dimethylbarbituric acid with allylacetate. 5-Allyl-1,5-dimethylbarbituric acid was obtained with an optical induction of up to 12.7% ee.     

Synthesis of a series of ganglioside GM3 analogs containing a deoxy-N-acetylneuraminic acid residue.

Ganglioside GM₃ analogs containing 4-, 7-, 8-, and 9-deoxy-N-acetylneuraminic acids in the place of N-acetylneuraminic acid (Neu5Ac) have been synthesized. Glycosylation of 2-(trimethylsilyl)ethyl O-(6-O-benzoyl-β- - galactopyranosyl)-(1 → 4)-2,6-di-O-benzoyl-β- -glucopyranoside with the methyl 2-thioglycoside derivatives of the respective deoxy-N-acetylneuraminic acids, using dimethyl(methylthio)sulfonium triflate as a promoter, gave the four required 2-(trimethylsilyl)ethyl -sialosyl-(2 → 3b)-β-lactosides. These were converted via O-acetylation, selective removal of the 2-(trimethylsilyl)ethyl group, and subsequent imidate formation, into the corresponding -sialosyl-(2 → 3b)--lactose trichloroacetimidates 15, 17, 19, and 21. Glycosylation of (2S,3R,4E)-2-azido-3-O-benzoyl-4-octadecene-1,3-diol with 15, 17, 19, and 21 in the presence of boron trifluoride etherate afforded the expected β glycosides, which were transformed in good yields, via selective reduction of the azido group, coupling with octadecanoic acid, O-deacylation, and de-esterification, into the target compounds.