Synthesis of an RGD‐Sialyl‐Lewis^X Glycoconjugate: A New Highly Active Ligand for P‐Selectin^**

Abstract

only deviate slightly from the C,AIOAIC, plane; each hydrogen atom projects into the space between the two trimethylsilyl groups of the neighboring carbon atom.The fast rotation about the AI-C bond in solution results in only one N M R signal for the methyl and methine groups. These signals remain virtually unchanged on cooling a solution of 2 in toluene to -80 ' C . The methine protons of 2 (6 = -0.54) resonate far upfield from the corresponding protons in the starting material 1 (6 = 0.36), and lie in the range between the values of threefold (6 = -0.20 to -0.45) and fourfold (6 < -0.55) coordinated bis(trimethy1silyl)methylaluminum compounds.[201 The resonance of the C atom bonded to Al (6 = 9.0) also lies at a higher field than that in compounds with Al atoms having threefold coordination (R,AI-S-AIR,:[51 6 = 16.6; R,AI-Te-AIR,:['] 6 = 17.3); this corresponds to an increase of the charge density on the Al atoms. In analogy to the situation in organoboron compounds (Me,BOR or Me,BNR,),[2t1 these data possibly verify the participation of a mesomeric structure with A I L 0 II interactions between the lone pairs of electrons on oxygen and the empty p orbitals on Al."61 Esperimen tal Procedure I (1 2 4 g. 1.8 mmol) was dissolved under argon in ti-hexane (50 mL. freshly distilled over butyllithiuin) and treated with diinethyt sulfoxide (0.127 mL. 1.8 mmol. distilled over BaO) at room temperature with vigorous stirring. After about 30 min the solution had completely decolorized. The volume of the solution was reduced by half (in viicuo) and the optimal amount of isobutyllithium added (experimentally predetermined: here. 0.84 m L (0.72 mmol) of a 0 . 8 5 7~ solution in n-pentnne). Colorless crystals of 2 were obtained on cooling to -50°C. Yield: 0.95 g (75%). M.p. (under Ar): 173 C: M ,

Synthetic Glycopeptides of the Tandem Repeat Sequence of the Epithelial Mucin MUC4 with Tumour-associated Carbohydrate Antigens

“…9a,20 Similar to this latter reaction, all Fmoc protected tumourassociated T, sialyl-T N , (2,6)-and (2,3)-sialyl-T antigen threonine building blocks have been synthesized in the Like in the regioselective sialylation 9a with xanthate 4 of O-acetyl protected sialic acid benzyl ester, the tert-butyl ester also remained untouched during the introduction of the 4,6-benzylidene group in acetonitrile at room temperature (yield of 7: 75%) as well as the 4,6-(4-methoxy-benzylidene) group in dimethylformamide at 50°C in the presence of catalytic amounts of p-toluenesulfonic acid. The subsequent galactosylation of 8 with tetra-O-acetylgalactopyranosyl bromide to give 9 (86%) and of 7 using 6-O-benzyl-2,3,4-tri-O-acetyl-galactosyl bromide 22 to afford 10 (93%) were achieved best by promotion with Hg(CN) 2 according to Helferich. 23 The formation of 10 was neither satisfactorily achieved with the corresponding thioglycosides, 24 nor by activation of the glycosyl bromide with silver triflate 25 or by using the trichloroacetimidate.…”

Trichloroacetimidates

“…Fucosylation of a similar O-benzylideneprotected glucosamine acceptor performed well with a thioglycoside donor [74-761, but the galactosylation was critical because of the steric hindrance of the 4-OH group. The methylthio galactoside donor gave a 16% yield [74]; the trichloroaceti- …”

Glycopeptide Synthesis in Solution and on the Solid Phase

“…They can be: 1) produced on a gram scale; 2) easily converted into the corresponding P-glycosylamino derivatives and 3 ) efficiently coupled to form stable amide linkages. In this manner, SLe" amine 53 was combined with a tetrapeptide partial sequence from fibrinogen required for binding to the integrin receptor GpIIb [29]. For this conjugation the C-terminal alanine of RGDA derivative 54 served the as coupling position (Scheme 26).…”