Synthesis of optically active lipidicα-amino acids and lipidic 2-amino alcohols

Summary Lipidic-amino acids (LAAs) are a class of compounds combining structural features of amino acids with those of fatty acids. They are non-natural-amino acids with saturated or unsaturated long aliphatic side chains. Synthetic approaches to optically active LAAs and lipidic 2-amino alcohols (LAALs) are summarized in this review. A general approach to enantioselective synthesis of saturated LAAs is based on the oxidative cleavage of 3-amino -1,2-diols obtained by the regioselective opening of enantiomerically enriched long chain 2,3-epoxy alcohols. Unsaturated LAAs are prepared in their enantiomeric forms by Wittig reactionvia methyl (S)-2di-tert-butoxycarbonylamino-5-oxo-pentanoate. This key intermediate aldehyde is obtained by selective reduction of dimethyl N,N-di-Boc glutamate with DIBAL. (R) or (S) LAALs may be prepared starting from D-mannitol or L-serine. LAAs are converted into LAALs by chemoselective reduction of their fluorides using sodium borohydride with retention of optical purity. Replacement of the hydroxyl group of LAALs by the azido group, followed by selective reduction leads to unsaturated optically active lipidic 1,2-diamines.Abbreviations Bn benzyl - Boc tert-butoxycarbonyl - DDQ 2,3-dichloro-5,6-dicyano-1,4-benzoquinone - DET diethyl tartrate - DIBAL diisobutyl aluminum hydride - DMAP 4-dimethylaminopyridine - DMF N,N-dimethylformamide - DMSO dimethyl sulfoxide - EDC N-ethyl-N-(3-dimethylaminopropyl)carbodiimide - Et₃N triethylamine - HMPA hexamethylphosphoramide - HOBt 1-hydroxybenzotriazole - KN(TMS)₂ potassium bis(trimethylsilyl)-amide - LAA lipidic-amino acid - LAAAl lipidic 2-amino alcohol - LDA lipidic 1,2-diamine - LP lipidic peptide - MPM-Cl p-methoxybenzyl chloride - MsCl methanesulphonyl chloride - MTPA -methoxy--(trifluoromethyl)phenylaccitc - PLA₂ phospholipase A₂ - TBIIP tert-butyl hydroperoxide - THF tetrahydrofuran - TMSCl trimethylsilyl chloride - Tr trityl - Z benzyloxycarbonyl     

Synthesis of symmetric and asymmetric diamides of citric acid and amino acids

Summary A convenient method for the synthesis of symmetric and asymmetric diamides of amino acids including DOPA and citric acid from 2-tert-butyl-1,3-di(N-hydroxysuccinimidyl)citrate and 1-tert-butyl-2,3-di(N-hydroxysuccinimidyl)citrate is described.Abbreviations AcOtBu tert-butyl acetate - i-Bu iso-butyl - tBu tert-butyl - Bzl benzyl - p-OH-Bzl p-hydroxybenzyl - m,p-(OH)₂-Bzl m,p-dihydroxybenzyl - DCCI dicyclohexylcarbodiimide - Et ethyl - Me methyl - Su succinimidyl - SuOH N-hydroxysuccinimide - Ph phenyl     

Synthesis of medicinally useful lipidicα-amino acids, 2-amino alcohols and diamines

Summary The lipidic-amino acids (LAAs) are non-natural-amino acids with saturated or unsaturated long aliphatic side chains. LAAs and their derivatives (lipid mimetics) together with the lipidic peptides represent a class of compounds which combine structural features of lipids with those of amino acids and peptides. Racemic LAAs may be prepared by classical methods and resolved by chemical or enzymatic methods. LAA amides and esters with saturated or unsaturated long chain amines and alcohols respectively, as well as lipidic dipeptide derivatives inhibit both pancreatic and human platelet phospholipase A₂. Lipophilic peptide derivatives are inhibitors of human neutrophil elastase. LAAs and their oligomers have been used as drug delivery system. A Lipid-Core-Peptide system has been designed and used as a combined adjuvant-carrier-vaccine system. A variety of lipid mimetics such as lipidic 2-amino alcohols, lipidic 1,2- and 1,3-diamines have been prepared based upon LAAs. Some of them are potent inhibitors of phospholipase A₂. A general approach to enantioselective synthesis of LAAs and lipid mimetics is based on the oxidative cleavage of 3-amino-1,2-diols obtained by the regioselective opening of enantiomerically enriched long chain 2,3-epoxy alcohols.Abbreviations Boc tert-butoxycarbonyl - BSA bovine serum albumin - CD circular dichroism - DET diethyl tartrate - DIBAL diisobutyl aluminum hydride - DMF N,N-dimethylformammide - HMPA hexamethylphosphoramide - HNE human neutophil elastase - LAA lipidic amino acid - LAAL lipidic amino alcohol - LH-RH luteinizing hormone-releasing hormone - LCP lipid-core-peptide - LDA lipidic diamine - LP lipidic peptide - MAP multiple antigenic peptide - PLA₂ phospholipase A₂ - TBHP tert-butyl hydroperoxide - THF tetrahydrofuran - TRH thyrotropin-releasing hormone - Z benzyloxycarbonyl     

Synthesis and use of <Emphasis Type="Italic">N</Emphasis>,<Emphasis Type="Italic">N</Emphasis>-di-Boc-glutamate γ-semialdehydes and related aldehydes

Summary.  This review article focuses on the synthesis and reactions of N,N-di-Boc glutamate and aspartate semialdehydes as well as related aldehydes. These building blocks are prepared according to various strategies from glutamic and aspartic acids and find interesting synthetic applications. In the first part, the methods for the synthesis of N,N-di-Boc-amino aldehydes are summarized. The applications of these chiral synthons for the synthesis of unnatural amino acids and other bioactive compounds are discussed in the second section. Received April 24, 2002 Accepted August 13, 2002 Published online January 30, 2003 Authors' address: Prof. Violetta Constantinou-Kokotou, Chemical Laboratories, Agricultural University of Athens, Iera Odos 75, 11855 Athens, Greece, E-mail: vikon@aua.gr Abbreviations: AcNH-TEMPO, 4-acetamido-2,2,6,6-tetramethyl-1-piperidinyloxy free radical; AIBN, 2,2′-azobis(2-methylpropionitrile); Aliquat, methyltrioctylammonium chloride; Bn, benzyl; Boc, tert-butoxycarbonyl; Bu^t, tert-butyl; m-CPBA, 3-chloroperoxybenzoic acid; DAST, diethylaminosulfur trifluoride; DBU, 1,8-diazabicyclo[5.4.0]undec-7-ene; (R,R)-(+)-DET, (R,R)-(+)-diethyltartrate; DIBALH, diisobutyl aluminium hydride; DMAP, 4-dimethylaminopyridine; DMF, dimethylformamide; Et₃N, triethylamine; KHMDS, potassium bis(trimethylsilyl)amide; (S)-LLB, lanthanium-lithium-bis-metallic binaphthol catalyst; MsCl, methanesulfonyl chloride; NEM, N-ethylmorpholine; NMO, 4-methylmorpholine N-oxide; PPA, propylphosphonic acid anhydride; TBHP, tert-butyl hydroperoxide; TFA, trifluoroacetic acid; THF, tetrahydrofuran; TMSI, 1-(trimethylsilyl)imidazole; Trt, trityl.     

Anaerobic degradation of trans-cinnamate and ω-phenylalkane carboxylic acids by the photosynthetic bacterium Rhodopseudomonas palustris: evidence for a β-oxidation mechanism

The mechanism responsible for the initial steps in the anaerobic degradation of trans-cinnamate and -phenylalkane carboxylates by the purple non-sulphur photosynthetic bacterium Rhodopseudomonas palustris was investigated. Phenylacetate did not support growth and there was a marked CO₂ dependence for growth on acids with greater side-chain lengths. Here, CO₂ was presumably acting as a redox sink for the disposal of excess reducing equivalents. Growth on benzoate did not require the addition of exogenous CO₂. Aromatic acids with an odd number of side-chain carbon atoms (3-phenylpropionate, 5-phenylvalerate, 7-phenylheptanoate) gave greater apparent molar growth yields than those with an even number of side-chain carbon atoms (4-phenylbutyrate, 6-phenylhexanoate, 8-phenyloctanoate). HPLC analysis revealed that phenylacetate accumulated and persisted in the culture medium during growth on these latter compounds. Cinnamate and benzoate transiently accumulated in the culture medium during growth on 3-phenylpropionate, and benzoate alone accumulated transiently during the course of trans-cinnamate degradation. The transient accumulation of 4-phenyl-2-butenoic acid occurred during growth on 4-phenylbutyrate, and phenylacetate accumulated to a 1:1 molar stoichiometry with the initial 4-phenylbutyrate concentration. It is proposed that the initial steps in the anaerobic degradation of trans-cinnamate and the group of acids from 3-phenylpropionate to 8-phenyloctanoate involves -oxidation of the side-chain.Abbreviation 3-PP 3-phenylpropionic acid - 4-PB 4-phenylbutyric acid - 5-PV 5-phenylvaleric acid - 6-PH 6-phenylhexanoic acid - 7-PH 7-phenylheptanoic acid - 8-PO 8-phenyloctanoic acid - 4-P2B 4-phenyl-2-butenoic acid - GC/MS Gas chromatography/Mass spectrometry - HPLC High-pressure liquid chromatography     

Strategy and Design of Novel Reagents for the Fluorometric Analysis of Biomolecules

This article covers molecular designs to develop several new fluorometric reagents and their applications to increase the sensitivities up to the picomole level using HPLC for the measurement of biomolecules. The methods were designed to demonstrate the physiological activities, for example (1) N-(9-acridinyl)maleimide (NAM) for the measurement of SH, –S–S–, and sulfite such as cysteine, (2) diphenyl-1-pyrenylphosphine (DPPP) for the hydroperoxides in lipids, serum, tissues, and foodstuffs, (3) 9-bromomethylacridine (9-BrMA), (4) 2-(anthracene-2,3-dicarboxylimide)ethyltrifluoromethane sulfonate (AE-OTf) for carboxylic acids, and (5) The chiral fluorometric labelling reagent (S)-( + )-2-tert-butyl-2-methyl-1,3-benzodioxole-4-carboxylic acid (TBMB) to identify the chiralities of amino acids, sugars, and mono- and diacylglycerols.     

Relationship of amino acid sequence to immunological activity — syntheses and structure-activity relationships of thymosinβ 4 family

Summary Four peptides related to thymosin ₄ family and its six fragments were synthesized by the solution method. Among them, the four peptides related to thymosin ₄ family and its two fragments were found to have restoring activity on the impaired blastogenic response of T-lymphocytes isolated from uremic patients, but the other four fragments had no effect. Studies on the structureactivity relationships suggest that the tricosapeptide moiety corresponding to amino acids 16–38 of thymosin ₄ is found to be an important moiety on impaired immunological deficiency.Amino acids and their derivatives used in this investigations were of the L-configuration. The following abbreviations are used: DMF, dimethylformamide; DMSO, dimethylsulfoxide; Boc, tert-butoxycarbonyl; Z, benzyloxycarbonyl; NP, p-nitrophenyl; ONp, p-nitrophenyl ester; OBzl, benzyl ester; Bzl, benzyl; Troc,,,-tricloroethoxycarbonly; Su, N-hydroxysuccinimide; NMM, N-methylmorpholine; OSu, N-hydroxysuccinimide ester; WSCI, l-ethyl-3; (3-dimethylaminopropyl) carbodiimide; HOBT, N-hydroxybenzotriazole; TFA, trifluoroacetic acid; TLC, thin-layer chromatography; E-rosette, a rosette with sheep erythrocytes; EDTA, ethylenediaminetetraacetic acid; PHA, phytohemagglutinin; HPLC, high-performance liquid chromatography; ONb, p-nitrobenzyl ester; DCC, dicyclohexyl-carbodiimide.     

An approach for fluorometric determination of glycosyltransferase activities

A new strategy for the fluorometric determination of glycosyltransferase activities is reported. The method involves dansyl chloride derivatization of the reduced form (pNH₂phenyl) of a hydrophobic, aglycon moiety covalently linked to a number of acceptor substrates (pNO₂phenyl). Focusing on the Golgi enzyme core 2N-acetylglucosaminyltransferase, we found that synthesis and fractionation of the dansylated substrate derivative were rapid, easy and inexpensive. Additionally, the corresponding enzyme assay proved reproducible and very sensitive, as 0.4 pmol of reaction product were readily detected. This fluorometric approach appears therefore to be a valid tool for investigating the monitoring differential expression of glycosyltransferases exhibiting low levels of enzyme activity.Abbreviations T transferase - Gal D-N-galactose - GlcNAc D-N-acetylglucosamine - GalNAc D-N-acetylgalactosamine - HPLC high pressure liquid chromatography - UDP uridine diphosphate - TES 2-{[2-hydroxy-1,1-bis(hydroxymethyl)ethyl]amino}ethanesulfonic acid - pNp para-nitrophenyl - NMR nuclear magnetic resonance - DMSO dimethyl sulphoxide     

β-1-3- and β-1-4-glucan synthesis by membrane fractions from the fungus Saprolegnia

The -glucan synthetase activity of the fungus Saprolegnia monoica was assayed by supplying UDP-glucose to membrane fractions of mycelial homogenate. The analysis of glucan products by hydrolysis with various -glucanases and by chromatography show that both -1-3- and -1-4-linkages are formed at high substrate concentrations. In the absence of MgCl₂, -1-3-linked glucans are mainly produced. By increasing MgCl₂ concentrations the total synthesis activity and -1-3-linkages production are reduced. At low substrate concentrations in the presence of MgCl₂, -1-4-linked glucans are the only polysaccharide synthesized. Electron microscopy of radioactive products, synthesized by original membrane fractions or by membrane fractions isolated from continuous sucrose density gradients, shows microfibrils when the assays are conducted at high substrate concentrations in the absence of MgCl₂.Abbreviations G.S. I glucan synthetase I - G.S. II glucan synthetase II - Dol. P dolichol phosphate     

In-vivo formation of xyloglucan nonasaccharide: A possible biologically active cell-wall fragment

The in-vivo formation of a specific nonasaccharide of xyloglucan was investigated. This nonasaccharide has been reported to have biological activity, inhibiting auxin-induced growth in pea stem segments. Cell-suspension cultures of spinach were grown in the presence of [³H]arabinose and [³H]fucose, and the culture-filtrates were examined for oligosaccharides by gelpermeation chromatography and by paper chromatography. Sixteen [³H]pentose-containing oligosaccharides were found, including twelve that contained the sequence [³H]xylosyl-(16)-glucose, which is diagnostic of xyloglucan. In addition, [³H]fucose-containing oligosaccharides of at least three sizes were found. Radiochemical evidence is presented that one of these oligosaccharides was labelled with both [³H]fucose and with [³H]pentose, and was identical with the major xyloglucan-derived nonasaccharide associated with anti-auxin activity. It was largely present in the form of acylated (possibly acetylated) derivatives. It accumulated extracellularly to a steady-state concentration of about 4.3·10^-7M. This is the first report of the production of a biologically-active oligosaccharide by living plant cells.Abbreviations BAB butanone/acetic acid/H₃BO₃-saturated water (9:1:1) - BAW butan-1-ol/acetic acid/water (12:3:5) - BPW butan-1-ol/pyridine/water/(4:3:4) - DP degree of polymerisation - FAW ethyl acetate/acetic acid/water (10:5:6) - EPW ethyl acetate/pyridine/water (8:2:1) - k _av elution volume relative to Blue Dextran (k _av.=0.0) and glucose (k _av.=1.0) - XG7 XG9 minus the fucose and galactose residues - XG9 the particular xyloglucan nonasaccharide illustrated in Fig. 1 - W water-saturated phenol     

Enzymatic preparation of a carbohydrate ester of medium-chain fatty acid in supercritical carbon dioxide

Acylation of methyl--d-fructofuranoside and caprylic acid with an immobilized lipase, Novozym 435, was carried out in supercritical carbon dioxide (SCCO₂) with tert-butanol as a co-solvent. Initial rate of acylation was 12-fold higher in SCCO₂ than in tert-butanol. The equilibrium conversion was increased up to 70% with an increase in the molar ratio up to a maximum of 1:20 (methyl--d-fructofuranoside:caprylic acid) at 16 MPa and 70 °C.     

Inhibition of auxin-stimulated growth of pea stem segments by a specific nonasaccharide of xyloglucan

Hemicellulose extracted from cell walls of suspension-cultured rose (Rosa Paul's Scarlet) cells was digested with cellulase from Trichoderma viride. The quantitatively major oligosaccharide products, a nonasaccharide and a heptasaccharide derived from xyloglucan, were purified by gel permeation chromatography. The nonasaccharide was found to inhibit the 2,4-dichlorophenoxy-acetic-acid-induced elongation of etiolated pea (Pisum sativum) stem segments. This confirms an earlier report (York et al., 1984, Plant Physiol. 75, 295–297). The inhibition of elongation by the nonasaccharide showed a maximum at around 10^-9M with higher and lower concentrations being less effective. The heptasaccharide did not significantly inhibit elongation at 10^-7–10^-10M and also did not affect the inhibition caused by the nonasaccharide when co-incubated with the latter.Abbreviations 2,4-D 2,4-dichlorophenoxyacetic acid - XG xyloglucan - XG7 xyloglucan heptasaccharide (Glc₄·Xyl₃) - XG9 xyloglucan nonasaccharide (Glc₄·Xyl₃·Gal·Fuc)     

Isolation and characterization of an ω3-desaturation-defective mutant of an arachidonic acid-producing fungus,Mortierella alpina 1S-4

A mutant considered to be defective in the conversion of n-6 to n-3 fatty acids (3-desaturation) was derived from a 5-desaturation-defective mutant (Mut44) of Mortierella alpina 1S-4, after treating its spores with N-methyl-N-nitro-N-nitrosoguanidine. This mutant cannot produce 8(Z),11(Z),14(Z),17(Z)-eicosatetraenoic acid or any other n-3 fatty acids, of which about 10% was found in its parental strain upon cultivation at 12°C. The mutant's growth rate was comparable to that of the parental strain when grown at 28°C, but it became much slower when the mutant grew at 12°C, at which the lag phase for Mut44 was about 2 d but 5 d for the mutant.Abbreviations 18:33 9(Z),12(Z),15(Z)-octadecatrienoic acid - 18:43 6(Z),9(Z),12(Z),15(Z)-octadecatetraenoic acid - 20:43 8(Z),11(Z),14(Z),17(Z)-eicosatetraenoic acid - AA arachidonic acid - DHGA dihomo--linolenic acid - EPA 5(Z),8(Z),11(Z),14(Z),17(Z)-eicosapentaenoic acid - GLC gas-liquid chromatography - MNNG N-methyl-N-nitro-N-nitrosoguanidine - PC phosphatidylcholine     

Phenyl methyl ethers: novel electron donors for respiratory growth of<Emphasis Type="Italic"> Desulfitobacterium hafniense</Emphasis> and<Emphasis Type="Italic"> Desulfitobacterium</Emphasis> sp. strain PCE-S

Desulfitobacterium hafniense and Desulfitobacterium sp. strain PCE-S grew under anoxic conditions with a variety of phenyl methyl ethers as electron donors in combination with fumarate as electron acceptor. The phenyl methyl ethers were O-demethylated to the corresponding phenol compounds. O-demethylation was strictly dependent on the presence of fumarate; no O-demethylation occurred with CO₂ as electron acceptor. One mol phenyl methyl ether R-O-CH₃ was O-demethylated to R-OH per 3 mol fumarate reduced to succinate. The growth yields with vanillate or syringate plus fumarate were approximately 15 g cells (dry weight) per mol methyl moiety converted. D. hafniense utilized vanillate or syringate as an electron donor for reductive dehalogenation of 3-Cl-4-hydroxyphenylacetate, whereas strain PCE-S was not able to dechlorinate tetrachloroethene with phenyl methyl ethers. Crude extracts of both organisms showed O-demethylase activity in the O-demethylase assay with vanillate or syringate as substrates when the organism was grown on syringate plus fumarate. Besides the homoacetogenic bacteria, only growing cells of Desulfitobacterium frappieri PCP-1 have thus far been reported to be capable of phenyl methyl ether O-demethylation. This present study is the first report of Desulfitobacteria utilizing phenyl methyl ethers as electron donors for fumarate reduction and for growth.Abbreviations PCE Tetrachloroethene - TCE Trichloroethene - DCE cis-1,2-Dichloroethene - ClOHPA 3-Cl-4-Hydroxyphenylacetate - OHPA 4-Hydroxyphenylacetate - FH₄ Tetrahydrofolate     

Reactive oxygen species in choline deficiency induced carcinogenesis and nitrone inhibition

Reactive oxygen species and free radical processes have been considered important in cancer development for many years. Much research demonstrates that the choline-deficiency induced hepatocarcinogenesis model prominently involves reactive oxygen species. We present a summary of results obtained in our original studies of this model over the last 4 years. We have shown that -phenyl-tert-butyl nitrone (PBN) and some of its hydroxylated derivatives (the 4- and 3-hydroxylated compounds) prevent hepatocarcinogenesis in this model. Mechanistic studies have demonstrated that isolated mitochondria from the livers of rats fed the choline-deficiency defined amino acid diet produce significantly much more H₂O₂ per NADH reducing equivalents oxidized. Based on these observations, we postulate that H₂O₂ is a primary carcinogenic factor in this model. Based on studies of the action of PBN on isolated mitochondria, we postulate that the inhibiting action of PBN involves suppression of H₂O₂ production of mitochondria and generally decreasing the oxidative stress within the preneoplastic lesions. The net effect of the activity of the nitrone compounds appears to be due to their ability to shift the apoptosis/neoplastic tendency balance toward apoptosis of the cells within the preneoplastic lesions. This is considered to be the primary reason the size of the preneoplastic lesions are significantly decreased and why the nitrones are potent anti-carcinogenic agents in this model.     

Chemical composition of the lipopolysaccharides of Ectothiorhodospira shaposhnikovii,Ectothiorhodospira mobilis,and Ectothiorhodospira halophila

Lipopolysaccharides were isolated from the moderate halophilic Ectothiorhodospira shaposhnikovii slight to and Ectothiorhodospira mobilis and from the extremely halophilic Ectothiorhodospira halophila by the hot phenol-water and purified by the phenol-chloroform-petroleum ether methods. The isolated lipopolysaccharides of all three species contained 3-deoxy-d-manno-octulosonic acid and d-glycero-d-mannoheptose indicating the existence of a core. They contained additionally glucose and uronic acids (E. shaposhnikovii and E. mobilis) or glucose, uronic acids and threonine (E. halophila). Sodium deoxycholate gel-electrophoresis of the three lipopolysaccharides, each showing only one major band, indicated R-type character of the lipopolysaccharides of the three Ectothiorhodospira species.The lipid A fractions of the lipopolysaccharides from E. shaposhnikovii and E. mobilis represented phosphorylated mixed lipid A types with both 2,3-diamino-2,3-dideoxy-d-glucose and d-glucosamine. The lipid A from E. halophila contained also phosphate and 2,3-diamino-2,3-dideoxy-d-glucose but only traces of d-glucosamine, which would indicated lipid A_DAG. The fatty acid spectra were characterized by amide-bound 3-OH-10:0 and 3-OH-12:0 (E. shaposhnikovii), 3-OH-10:0 (E. mobilis), or 3-OH-10:0,3-OH-14:0, and 3-oxo-14-0 (E. halophila). The predominant ester-bound fatty acids were 14:0 and 16:0 (E. shaposhnikovii and E. mobilis), or 12:0 and 14:1 (E. halophila).Abbreviations DAG 2,3-diamino-2,3-dideoxy-d-glucose - Kdo 3-deoxy-d-manno-octulosonic acid - GlcA glucuronic acid - GalA galacturonic acid - GC-MS combined gas liquid chromatographymass spectrometry - GlcN Glucosamine - DOC sodium deoxycholate - LPS lipopolysaccharide - PAGE polyacrylamide gel electrophoresis - PCP phenol-chloroform-petroleum ether     

A fast and simplein situ method for the determination of the absolute configuration of amino acid esters using the chiroptical properties of their Eu(FOD)3 complexes

Summary The NMR shift reagent, Europium(III)-tris-(1,1,1,2,2,3,3)-heptafluoro-7,7-dimethyl-4-6-octanedione [Eu(fod)₃], complexes efficiently with-amino acid esters in chloroform. These complexes exhibit characteristic circular dichroism (CD) spectral patterns in the 350-250 nm region. A fast and simple procedure (also in microscale) has been worked out which utilizes the signs of these CD bands for the determination of the absolute configuration at the-carbon atomin situ. In the L-series, a positive CD band is observed at around 310 nm and a negative one in the 290-280 nm region. The CD spectra of the Eu complexes of the D-isomers are mirror images of those of the L-configurations. An empirical rule is proposed.Presented in part at the 2nd International Congress on Amino Acids and Analogues, Vienna, Austria, August 5–9, 1991.     

Synthesis of Neu5Ac- and Neu5Gc-α-(2→6′)-lactosamine 3-aminopropyl glycosides

In order to prepare 3-aminopropyl glycosides of Neu5Ac-α-(2→6′)-lactosamine trisaccharide 1, and its N-glycolyl containing analogue Neu5Gc-α-(2→6′)-lactosamine 2, a series of lactosamine acceptors with two, three, and four free OH groups in the galactose residue was studied in glycosylations with a conventional sialyl donor phenyl [methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-2-thio- -glycero-α- and β- -galacto-2-nonulopyranosid]onates (3) and a new donor phenyl [methyl 4,7,8,9-tetra-O-acetyl-5-(N-tert-butoxycarbonylacetamido)-3,5-dideoxy-2-thio- -glycero-α- and β- -galacto-2-nonulopyranosid]onates (4), respectively. The lactosamine 4′,6′-diol acceptor was found to be the most efficient in glycosylation with both 3 and 4, while imide-type donor 4 gave slightly higher yields with all acceptors, and isolation of the reaction products was more convenient. In the trisaccharides, obtained by glycosylation with donor 4, the 5-(N-tert-butoxycarbonylacetamido) moiety in the neuraminic acid could be efficiently transformed into the desired N-glycolyl fragment, indicating that such protected oligosaccharide derivatives are valuable precursors of sialo-oligosaccharides containing N-modified analogues of Neu5Ac.