Preparation and Structure of β-Peptides Consisting of Geminally Disubstituted β2,2- and β3,3-Amino Acids: A Turn Motif for β-Peptides

We report on the synthesis of new and previously described β-peptides ( 1 – 6 ), consisting of up to twelve β^2,2- or β^3,3-geminally disubstituted β-amino acids which do not fit into any of the secondary structural patterns of β-peptides, hitherto disclosed. The required 2,2- and 3,3-dimethyl derivatives of 3-aminopropanoic acid are readily obtained from 3-methylbut-2-enoic acid and ammonia (Scheme 1) and from Boc-protected methyl 3-aminopropanoate by enolate methylation (Scheme 2). Protected (Boc for solution-, Fmoc for solid-phase syntheses) 1-(aminomethyl)cycloalkanecarboxylic-acid derivatives (with cyclopropane, cyclobutane, cyclopentane, and cyclohexane rings) are obtained from 1-cyanocycloalkanecarboxylates and the corresponding dihaloalkanes (Scheme 3). Fully ¹³C- and ¹⁵N-labeled 3-amino-2,2-dimethylpropanoic-acid derivatives were prepared from the corresponding labeled precursors (see asterixed formula numbers and Scheme 4). Coupling of these amino acids was achieved by methods which we had previously employed for other β-peptide syntheses (intermediates 18 – 23 ). Crystal structures of Boc-protected geminally disubstituted amino acids ( 16a – d ) and of the corresponding tripeptide ( 23a ), as well as NMR and IR spectra of an isotopically labeled β-hexapeptide ( 2a* ) are presented (Figs. 1 – 4) and discussed. The tripeptide structure contains a ten-membered H-bonded ring which is proposed to be a turn-forming motif for β-peptides (Fig. 2).     

β-Peptides: Synthesis by Arndt-Eistert homologation with concomitant peptide coupling. Structure determination by NMR and CD spectroscopy and by X-ray crystallography. Helical secondary structure of a β-hexapeptide in solution and its stability towards pepsin

The β-hexapeptide (H-β-HVal-β-HAla-β-HLeu)₂-OH ( 2 ) was prepared from the component L -β-amino acids by conventional peptide synthesis, including fragment coupling. A cyclo-β-tri- and a cyclo-β-hexapeptide were also prepared. The β-amino acids were obtained from α-amino acids by Arndt-Eistert homologation. All reactions leading to the β-peptides occur smoothly and in high yields. The β-peptides were characterized by their CD and NMR spectra (COSY, ROESY, TOCSY, and NOE-restricted modelling), and by an X-ray crystal-structure analysis. β-Sheet-type structures (in the solid state) and a compact, left-handed or (M) 3₁ helix of 5-Å pitch (in solution) were discovered. Comparison with the analogous secondary structures of α-peptides shows fundamental differences, the most surprising one at this point being the greater stability of β-peptide helices. There are structural relationships of β-peptides with oligomers of β-hydroxyalkanoic acids, and dissimilarities between the two classes of compounds are a demonstration of the power of H-bonding. The β-hexapeptide 2 is stable to cleavage by pepsin at pH 2 in H₂O for at least 60 h at 37°, while the corresponding α-peptide H-(Val-Ala-Leu)₂-OH is cleaved instantaneously under these conditions. The implication of the described results are discussed.     

‘Mixed’ β-peptides: A unique helical secondary structure in solution. Preliminary communication

β-Hexapeptides 1–5 and a β-dodecapeptide 6 with sequences containing two different types of β-amino acids (aliphatic proteinageous side chains in the 2- or in the 3-position) have been prepared. CD (Fig. 1) and NMR measurements indicate that, with one exception, the secondary structures formed by these new β-peptides differ from those of isomers studied previously. Detailed NMR analysis of the β-hexapeptide 5 (with alternating β²,β³-building blocks) and molecular-dynamics simulations have produced a minimum energy conformation (Fig. 2,b)which might be described as a novel irregular helix containing ten- and twelve-membered H-bonded rings. This demonstrates the great structural variability of β-peptides, since three different helical secondary structures have been discovered to date.     

(S)-β3-Homolysine- and (S)-β3-Homoserine-Containing β-Peptides: CD Spectra in Aqueous Solution

For further structural studies and for physiological investigations of β-peptides, it is necessary to have H₂O-soluble derivatives. Thus, we have prepared β-hexa-, β-hepta-, and β-nonapeptides ( 1 – 6 ) with two, three, and seven side chains of lysine and serine. To detect possible π-π interactions, we also included the β-amino acid β²-HHop, resulting from homologation of so-called homophenylalanine (Hop) ( 5 and 6 ). The Fmoc-β²- and β³-amino-acid derivatives ( 11 – 14 and 19 ), and the corresponding β-peptides were prepared by methods previously described (solid-phase peptide coupling; HPLC-pure samples, Fig. 1). Circular-dichroism spectra (Fig. 2) indicate the presence of less pronounced secondary structures (especially of the lysine analogues with multiple positive charge) in H₂O as compared to MeOH. The β³-heptapeptide ( 3 ) with two serine side chains is well soluble in H₂O and exhibits the CD pattern typical of the 3₁-helical structure.     

Probing the Helical Secondary Structure of Short-Chain β-Peptides

Structural prerequisites for the stability of the 3₁ helix of β-peptides can be defined from inspection of models (Figs. 1 and 2): lateral non-H-substituents in 2- and 3-position on the 3-amino-acid residues of the helix are allowed, axial ones are forbidden. To be able to test this prediction, we synthesized a series of heptapeptide derivatives Boc-(β-HVal-β-HAla-β-HLeu-Xaa-β-HVal-β-HAla-β-HLeu)-OMe 13–22 (Xaa = α- or β-amino-acid residue) and a β-depsipeptide 25 with a central (S)-3-hydroxybutanoic-acid residue (Xaa = –OCH(Me)CH₂C(O)–) (Schemes 1 3). Detailed NMR analysis (DQF-COSY, HSQC, HMBC, ROESY, and TOCSY experiments) in methanol solution of the β-hexapeptide H(-β-HVal-β-HAla-β-HLeu)₂-OH ( 1 ) and of the β-heptapeptide H-β-HVal-β-HAla-β-HLeu-(S,S)-β-HAla(αMe)-β-HVal-β-HAla- β-HLeu-OH ( 22 ), with a central (2S,3S)-3-amino-2-methylbutanoic-acid residue, confirm the helical structure of such β-peptides (previously discovered in pyridine solution) (Fig.3 and Tables 1–5). The CD spectra of helical β-peptides, the residues of which were prepared by (retentive) Arndt-Eistert homologation of the (S)- or L -α-amino acids, show a trough at 215 nm. Thus, this characteristic pattern of the CD spectra was taken as an indicator for the presence of a helix in methanol solutions of compounds 13–22 and 25 (including partially and fully deprotected forms) (Figs.4–6). The results fully confirm predicted structural effects: incorporation of a single ‘wrong’ residue ((R)-β-HAla, β-HAib, (R,S)-β-HAla(α Me), or N-Me-β-HAla) in the central position of the β-heptapeptide derivatives A (see 17, 18, 20 , or 21 , resp.) causes the CD minimum to disappear. Also, the β-heptadepsipetide 25 (missing H-bond) and the β-heptapeptide analogs with a single α-amino-acid moiety in the middle ( 13 and 14 ) are not helical, according to this analysis. An interesting case is the heptapeptide 15 with the central achiral, unsubstituted 3-aminopropanoic-acid moiety: helical conformation appears to depend upon the presence or absence of terminal protection and upon the solvent (MeOH vs. MeOH/H₂O).     

Preparation of Protected β2‐ and β3‐Homocysteine, β2‐ and β3‐Homohistidine,and β2‐Homoserine for Solid‐Phase Syntheses

The Ser, Cys, and His side chains play decisive roles in the syntheses, structures, and functions of proteins and enzymes. For our structural and biomedical investigations of β‐peptides consisting of amino acids with proteinogenic side chains, we needed to have reliable preparative access to the title compounds. The two β³‐homoamino acid derivatives were obtained by Arndt–Eistert methodology from Boc‐His(Ts)‐OH and Fmoc‐Cys(PMB)‐OH (Schemes 2–4), with the side‐chain functional groups' reactivities requiring special precautions. The β²‐homoamino acids were prepared with the help of the chiral oxazolidinone auxiliary DIOZ by diastereoselective aldol additions of suitable Ti‐enolates to formaldehyde (generated in situ from trioxane) and subsequent functional‐group manipulations. These include OH→O^tBu etherification (for β²hSer; Schemes 5 and 6), OH→STrt replacement (for β²hCys; Scheme 7), and CH₂OH→CH₂N₃→CH₂NH₂ transformations (for β²hHis; Schemes 9–11). Including protection/deprotection/re‐protection reactions, it takes up to ten steps to obtain the enantiomerically pure target compounds from commercial precursors. Unsuccessful approaches, pitfalls, and optimization procedures are also discussed. The final products and the intermediate compounds are fully characterized by retention times (t_R), melting points, optical rotations, HPLC on chiral columns, IR, ¹H‐ and ¹³C‐NMR spectroscopy, mass spectrometry, elemental analyses, and (in some cases) by X‐ray crystal‐structure analysis.     

The synthesis of β-heteroarylamino-α,β-dehydro-α-amino acid and β-heteroarylamino-α-amino acid derivatives

From heteroarylaminomethyleneoxazolones 4 , obtained from N-heteroarylformamidines 2 and 2-phenyl-5-oxo-4,5-dihydro-1,3-oxazole ( 3 ), the following β-heteroarylamino-α,β-dehydro-α-amino acid derivatives were prepared: methyl 8 and ethyl esters 9 , amides 10 and 11 , hydrazides 12 , and azides 15 . By catalytic hydrogenation the compounds 4 were converted into β-heteroarylamino substituted amides 18 and β-heteroarylamino-α-amino acids 20 .     

β-Peptides as Inhibitors of Small-Intestinal Cholesterol and Fat Absorption

Selective lipid transport through the brush-border membrane in the small intestine of mammals is mediated by membrane-bound proteins, the so-called scavenger receptors of class B, type I or II (SR-BI or -BII). These, in turn, are inhibited by certain proteins and synthetic α-peptides that have an amphipathic helix as the binding motif (Fig. 1). In whole cells (test with human colonic carcinoma cells, CaCo-2), on the other hand, the inhibitors are subject to proteolysis. We have now tested six β-peptides (hexa-, hepta-, and nonamers 1 – 6 ), each carrying one to seven water-solubilizing side chains of either Ser or Lys, with a brush-border-membrane (BBM) vesicle model system (rate and IC₅₀ values in Figs. 2 and 3) and with a tightly packed monolayer of CaCo-2 cells (rate in Fig. 4), to find that the rate of transport of cholesterol can be reduced to what may be considered the passive diffusion (`background') level. There is a correlation between the ability of the β-peptides to form an amphipathic-type 3₁₄-helical secondary structure in MeOH and their inhibitory effect (Table 1 and Fig. 5). Although the inhibitory activity of the β-peptides is in only the mM range (Table 2), it is to be compared with no activity at all of previously tested α-peptides and proteins (built of L -amino acids) in CaCo-2 cells. Furthermore, these active β-peptides ( 1 , 5 , and 6 ) contain only seven or nine residues and must be considered simple, first-generation models capable of mimicking the biological activity of amphipathic α-peptide helices in living whole cells.     

Pleated Sheets and Turns of β-Peptides with Proteinogenic Side Chains

Components of a toolbox with predictable secondary structural elements: β-peptides. The β-peptide shown here with proteinogenic side chains adopts a parallel pleated sheet structure in the solid state upon incorporation of suitably configured β-amino acids. When a β-dipeptide turn segment is incorporated in the center, a hairpin is formed in solution.     

Transformations of N-heteroarylformamidines into derivatives of β-heteroarylamino-α,β-dehydro-α-amino acids, β-heteroarylamino-α-amino acids,and dipeptides

Transformations of N'-heteroaryl-N,N-dimethylformamidines 1 as a general method for the preparation of β-heteroarylamino-α,β-dehydro-α-amino acids, β-heteroarylamino-α-amino acid derivatives 5–9 , and dipeptides 10 , are described.     

Synthese von diastereo- und enantio-selektiv deuterierten β,ε-, β,β-, β,γ- und γ,γ-Carotinen

Synthesis of Diastereo- and Enantioselectively Deuterated β,ε-, β,β-, β,γ- and γ,γ-Carotenes We describe the synthesis of (1′R, 6′S)-[16′, 16′, 16′-²H₃]-β, εcarotene, (1R, 1′R)-[16, 16, 16, 16′, 16′, 16′-²H₆]-β, β-carotene, (1′R, 6′S)-[16′, 16′, 16′-²H₃]-γ, γ-carotene and (1R, 1′R, 6S, 6′S)-[16, 16, 16, 16′, 16′, 16′-²H₆]-γ, γ-carotene by a multistep degradation of (4R, 5S, 10S)-[18, 18, 18-²H₃]-didehydroabietane to optically active deuterated β-, ε- and γ-C₁₁-endgroups and subsequent building up according to schemes \documentclass{article}\pagestyle{empty}\begin{document}${\rm C}_{11} \to {\rm C}_{14}^{C_{\mathop {26}\limits_ \to }} \to {\rm C}_{40} $\end{document} and C₁₁ → C₁₄; C₁₄+C₁₂+C₁₄→C₄₀. NMR.- and chiroptical data allow the identification of the geminal methyl groups in all these compounds. The optical activity of all-(E)-[²H₆]-β,β-carotene, which is solely due to the isotopically different substituent not directly attached to the chiral centres, is demonstrated by a significant CD.-effect at low temperature. Therefore, if an enzymatic cyclization of [17, 17, 17, 17′, 17′, 17′-²H₆]lycopine can be achieved, the steric course of the cyclization step would be derivable from NMR.- and CD.-spectra with very small samples of the isolated cyclic carotenes. A general scheme for the possible course of the cyclization steps is presented.     

Preparation of β2‐Homotryptophan Derivatives for β‐Peptide Synthesis

In view of the prominent role of the 1H‐indol‐3‐yl side chain of tryptophan in peptides and proteins, it is important to have the appropriately protected homologs H‐β² HTrp OH and H‐β³ HTrp OH (Fig.) available for incorporation in β‐peptides. The β²‐HTrp building block is especially important, because β²‐amino acid residues cause β‐peptide chains to fold to the unusual 12/10 helix or to a hairpin turn. The preparation of Fmoc and Z β²‐HTrp(Boc) OH by Curtius degradation (Scheme 1) of a succinic acid derivative is described (Schemes 2–4). To this end, the (S)‐4‐isopropyl‐3‐[(N‐Boc‐indol‐3‐yl)propionyl]‐1,3‐oxazolidin‐2‐one enolate is alkylated with Br CH₂CO₂Bn (Scheme 3). Subsequent hydrogenolysis, Curtius degradation, and removal of the Evans auxiliary group gives the desired derivatives of (R)‐H β²‐HTrp OH (Scheme 4). Since the (R)‐form of the auxiliary is also available, access to (S)‐β²‐HTrp‐containing β‐peptides is provided as well.     

Synthesis of β3‐Peptides and Mixed α/β3‐Peptides by Thioligation

Five β‐peptide thioesters ( 1 – 5 , containing 3, 4, 10 residues) were prepared by manual solid‐phase synthesis and purified by reverse‐phase preparative HPLC. A β‐undecapeptide ( 6 ) and an α‐undecapeptide ( 7 ) with N‐terminal β³‐HCys and Cys residues were prepared by manual and machine synthesis, respectively. Coupling of the thioesters with the cysteine derivatives in the presence of PhSH (Scheme and Fig. 1) in aqueous solution occurred smoothly and quantitatively. Pentadeca‐ and heneicosapeptides ( 8 – 10 ) were isolated, after preparative RP‐HPLC purification, in yields of up to 60%. Thus, the so‐called native chemical ligation works well with β‐peptides, producing larger β³‐ and α/β³‐mixed peptides. Compounds 1 – 10 were characterized by high‐resolution mass spectrometry (HR‐MS) and by CD spectroscopy, including temperature and concentration dependence. β‐Peptide 9 with 21 residues shows an intense negative Cotton effect near 210 nm but no zero‐crossing above 190 nm, (Figs. 2–4), which is characteristic of β‐peptidic 3₁₄‐helical structures. Comparison of the CD spectra of the mixed α/β‐pentadecapeptide ( 10 ) and a helical α‐peptide (Fig. 5) indicate the presence of an α‐peptidic 3.6₁₃ helix.     

Zn2+‐Complexation by a β‐Peptidic Helix and Hairpin Containing β3hCys and β3hHis Building Blocks: Evidence from CD Measurements. Preliminary Communication

Two new β³‐homohistidine‐ and β³‐homocysteine‐containing β‐peptides have been prepared by solid‐phase synthesis. A β‐octapeptide ( 2 ) contains seven β³‐amino acids and one β²‐amino acid. The β²/β³ segment has been placed in the middle of this peptide, which contains β³‐amino acids of alternating configuration, to induce the formation of a hairpin secondary structure. A β‐decapeptide ( 3 ) has been designed to fold to a 3₁₄‐helical secondary structure with neighboring His side chains in 6‐ and 9‐positions. Circular‐dichroism (CD) measurements show the capability of both peptides to bind Zn²⁺ ions in aqueous solution. In the case of the β‐octapeptide, binding of Zn²⁺ causes a dramatic change of the CD spectrum, indicating a change or a stabilization of its secondary structure. Zn²⁺ Ions clearly stabilize the 3₁₄‐helix of the β‐decapeptide, in neutral and basic solution. For the construction of the two new β‐peptides, we needed to have a supply of the β‐amino acid derivatives Fmoc‐β³hCys(Trt)‐OH and Fmoc‐β³hHis(Trt)‐OH, the preparation of which is described herein.     

Preparation of (S,S)‐Fmoc‐β2hIle‐OH, (S)‐Fmoc‐β2hMet‐OH,and (S)‐Fmoc‐β2hTyr(tBu)‐OH for Solid‐Phase Syntheses of β2‐ and β2/β3‐Peptides

The preparation of three new N‐Fmoc‐protected (Fmoc=[(9H‐fluoren‐9‐yl)methoxy]carbonyl) β²‐homoamino acids with proteinogenic side chains (from Ile, Tyr, and Met) is described, the key step being a diastereoselective amidomethylation of the corresponding Ti‐enolates of 3‐acyl‐4‐isopropyl‐5,5‐diphenyloxazolidin‐2‐ones with CbzNHCH₂OMe/TiCl₄ (Cbz=(benzyloxy)carbonyl) in yields of 60–70% and with diastereoselectivities of >90%. Removal of the chiral auxiliary with LiOH or NaOH gives the N‐Cbz‐protected β‐amino acids, which were subjected to an N‐Cbz/N‐Fmoc (Fmoc=[(9H‐fluoren‐9‐yl)methoxy]carbonyl) protective‐group exchange. The method is suitable for large‐scale preparation of Fmoc‐β²hXaa‐OH for solid‐phase syntheses of β‐peptides. The Fmoc‐amino acids and all compounds leading to them have been fully characterized by melting points, optical rotations, IR, ¹H‐ and ¹³C‐NMR, and mass spectra, as well as by elemental analyses.     

Synthesis of β‐Hexa‐ and β‐Heptapeptides Containing Novel β2,3‐Amino Acids with Two Serine or Two Cysteine Side Chains – CD‐ and NMR‐Spectroscopic Evidence for 314‐Helical Secondary Structures in Water

Two representatives of a new type of β‐amino acids, carrying two functionalized side chains, one in the 2‐ and one in the 3‐position, have been prepared stereoselectively: a β‐Ser derivative with an additional CH₂OH group in the 2‐position (for β‐peptides with better water solubility; Scheme 2) and a β‐HCys derivative with an additional CH₂SBn group in the 2‐position (for disulfide formation and metal complexation with the derived β‐peptides; Scheme 3). Also, a simple method for the preparation of α‐methylidene‐β‐amino acids is presented (see Boc‐2‐methylidene‐β‐HLeu‐OH, 8 in Scheme 3). The two amino acids with two serine or two cysteine side chains are incorporated into a β‐hexa‐ and two β‐heptapeptides ( 18 and 23/24 , resp.), which carry up to four CH₂OH groups. Disulfide formation with the β‐peptides carrying two CH₂SH groups generates very stable 1,2‐dithiane rings in the centre of the β‐heptapeptides, and a cyclohexane analog was also prepared (cf. 27 in Scheme 6). The CD spectra in H₂O clearly indicate the presence of 3₁₄‐helical structures of those β‐peptides ( 18 , 23 , 24 , 27b ) having the `right' configurations at all stereogenic centers (Fig. 2). NMR Measurements (Tables 1 and 2, and Fig. 4) in aqueous solution of one of the new β‐peptides ( 24 ) are interpreted on the assumption that the predominant secondary structure is the 3₁₄‐helix, a conformation that has been found to be typical for β‐peptides in MeOH or pyridine solution, according to our previous NMR investigations.     

Rhodium(II)-Catalyzed Decomposition of β,γ-Unsaturated Diazo Compounds

The Rh^II-catalyzed decomposition of β,γ-unsaturated diazo ketones 1 in the presence of MeOH leads via vinylogous Wolff rearrangement to γ,δ-unsaturated esters 6 (Schemes 1 and 2). A modest asymmetric induction is achieved when the reaction is carried out with chiral tetrakis(pyrrolidinecarboxylato)- or tetrakis(oxazolidinonato)dirhodium(II) complexes. Vinyl and phenyl diazoacetates 11 and 20 , respectively, or 1-diazo-3-phenyl-propan-2-one ( 25 ), when subjected to the same reaction conditions, react by OH insertion with MeOH (Schemes 3–5). In the absence of MeOH, phenyl diazoacetates 20 and 25 undergo intramolecular CH insertion to 22 and 26 , respectively. Intramolecular CH insertion occurs with N-aryldiazoamides 23 even in the presence of MeOH (Scheme 5).     

Synthesis and Self‐Assembly of Bolaamphiphiles Based on β‐Amino Acids or an Alcohol

The synthesis of bolaamphiphiles from unusual β‐amino acids or an alcohol and C₁₂ or C₂₀ spacers is described. Unusual β‐amino acids such as a sugar amino acid, an AZT‐derived amino acid, a norbornene amino acid, and an AZT‐derived amino alcohol were coupled with spacers under standard conditions to get the novel bolaamphiphiles 5 – 8 (Scheme 1), 12 and 13 (Scheme 2), and 17 and 20 (Scheme 3). Some of these compounds, on precipitation from MeOH/H₂O, self‐assembled into organized molecular structures.     

The Enantioselective Synthesis of β-Amino Acids,their α-hydroxy derivatives,and the N-terminal components of bestatin and microginin

L -Aspartic acid by tosylation, anhydride formation, and reduction with NaBH₄ was converted into (3S)-3-(tosylamino)butan-4-olide ( 8 ; Scheme 1). Tretment of 8 with ethanolic trimethylsilyl iodide gave the N-protected deoxy-iodo-β-homoserine ethyl ester 9 . The latter, on successive nucleophilic displacement with lithium dialkyl-cuprates ( → 10a–e ), alkaline hydrolysis ( → 11a–e ), and reductive removal of the tosyl group, produced the corresponding 4-substituted (3R)-3-aminobutanoic acids 12a–e (ee > 99%). Electrophilic hydroxylation of 8 ( → 19 ; Scheme 3), subsequent iodo-esterification ( → 21 ; Scheme 4), and nucleophilic alkylation and phenylation afforded, after saponification and deprotection, a series of 4-substituted (2S, 3R)-3-amino-2-hydroxybutanoic acids 24 including the N-terminal acids 24e ( = 3 ) and 24f ( = 4 ) of bestatin and microginin (de > 95%), respectively.     

Oligosaccharides Related to Tumor-Associated Antigens. Part I. Synthesis of the propyl glycoside of the trisaccharide α-L-Fucp-(1 → 2)-β-D-Galp-(1 → 3)-β-D-GalpNAc,component of a tumor antigen recognized by the antibody MBr1

The synthesis of the trisaccharide α-L -Fucp-(1 → 2)-β-D -Galp-(1 → 3)-β-D -GalpNAc-1-OPr ( 2 ) is described. The N-acetylgalactosamine 6 was obtained from 4 by an intramolecular displacement of a (trifluoromethyl)sulfonyloxy by a pivaloyloxy group with its concomitant migration from position 3 to position 4 (Scheme 1). The galactosyl donor 9 was obtained from 7 via 8 by regioselective opening of the orthoester function with AcOH/pyridine followed by treatment with CCl₃CN and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) (Scheme 2). Glycosylation of 6 with 9 in the presence of BF₃ · OEt₂ gave the disaccharide 10 . Selective deprotection of 10 at O? C(2′) followed by glycosylation with 12 and by standard deprotection afforded the title trisaccharide 2 (Scheme 3). Preliminary biological testing showed that 2 is able to inhibit the binding of the monoclonal antibody MBrl to the target tumor cells MCF7 in a dose-dependent manner.