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Phenyl boronate diester was used as a cleavable protecting group on thioglycoside donors. Procedures to glycosylate the polymer linker combination MPEG-DOXOH were developed. The boronate diester was readily removed and the resulting diols regioselectively glycosylated using silver triflate promotion of a trichloroacetimidate donor. Subsequent protecting group manipulations and cleavage from the polymer yielded peracetylated disaccharides in good yields. The whole sequence requires only one chromatography and is therefore much simpler than traditional procedures.The possibility of using oligosaccharides as therapeutic agents means there is a need to develop synthetic methods that are amenable to bulk production. This goal typically requires that all intermediates are purifiable without chromatography. One way to achieve this is to use polymer supports 1 such as the soluble polymer polyethylene glycol monomethyl ether (MeO-(CH 2 CH 2 O) n OH MW 5,000, MPEG) 2 with pdioxyxylene (-OCH 2 PhCH 2 O-, DOX) as a linker. 3 This method requires the development of glycosyl donor building blocks with cleavable protecting groups for chain extension. 4 The relatively stable DOX linker allows for base or mild acid cleavable protecting groups to be used. This communication describes the use of phenylboronate diesters as cleavable protecting groups on thioglycoside donors. 5 Scheme 1Thus, ethyl ß-D-galactothiopyranoside 1 prepared 6 from D-galactose without chromatography was converted in 94% yield into its crystalline 4,6-O-phenylboronate diester 2. A simple procedure developed by Ferrier 7 , consisting of adding a methanol solution of the polyol to a refluxing solution of phenylboronic acid in benzene under azeotropic conditions from which the product crystallizes after cooling, was used, see Scheme 1. The crystalline 2,3-dibenzoate 3 of 2 was used 8 to glycosylate MPEG-DOXOH under standard N-iodosuccinimide/triflic acid conditions. 9 The use of excess donor ensures almost quantitative conversion to 4. The reaction product is purified, as usual, by first precipitation from the reaction mixture with excess t-butylmethyl ether followed by recrystallization from absolute ethanol. Many boronate diesters are cleaved by alcoholysis, such as the glucose analogue of 4, see below, however diester 4 was not completely cleaved under these conditions. Complete removal of the boronate diester was achieved by gently shaking a dry acetonitrile solution of the MPEG polymer with the borate specific resin Amberlite-IRA-743 10 to give diol 5, see Scheme 2. Scheme 2Diol 5 could be regioselectively glycosylated by O-trichloroacetimidate GlcNAc donor 6 using silver triflate activation at 60 °C. 11 To the best of our knowledge this is the first example of silver triflate promoted glycosylation of a PEG bound acceptor with a trichloroacetimidate donor; analogous polymer free glycosylations proceed readily at room temperature suggesting an interaction of the silver triflate with the PEG. 11 Donor 6 was made without chromatography from glucosamine. 12 Th...

. Can. J. Chem. 52, 2648 (1974).A series of para-substituted 0-benzoyl-2-hydroxybutanoic acids (but not the unsubstituted ester) are hydrcijred by bovine carboxypeptidase A ( p H 7.5, ionic strength 0.5, 25"), For the CH,O, CH,, CI, CN, and NO2 substituents, there exist linear correlations of kc,, and K,,, with the Hammett o constants for these substituents (log kc,, = 1.170 f 1.17; log K,,, = -0.530 -2.15), although the tert-butyl group shows significant deviations from both correlation lines. The above unsubstituted ester is a reversible inhibitor of the enzymic hydrolysis of 0-hippuryl-L-3-phenyllactic acid and so the lack of observable hydrolysis of this ester is attributable to nonproductive binding. The pH-rate profiles for k,,,/K, and kc,, have been determined for the enzymic hydrolysis of 0-(p-nitrobenzoy1)mandelic acid (pKEH, = 6.95, pKEH = 7.9 and pKEH2, = 7.5, pKEHs = 8.3) and 0-hippuryl-L-3-phenyllactic acid (pKEH, = 5.8, pKEH = 9.3). For the latter ester kc,, is p H independent in the range p H 5-10. The mechanisrn of ester hydrolysis catalyzed by carboxypeptidase A is discussed in the light of the above observations and the known crystal structure of the enzyme. A definition of specific and nonspecific substrates for this enzyme based on the observed p H profiles for k,,,/K,,, is proposed. 52, 2648 (1974).Des series d'acides 0-benzoyl hydroxy-2 butanoi'ques substitues en para (rnais pas les esters non substitues) sont hydrolyses par la carboxypeptidase A du bovin (pH 7.5, 25', force ionique de @.5). I1 existe des correlations lineaires entre k,,,, K,,, et les constances o de Hammett des substituants CH,O, CH,, C1, C N et NO, (log kc,, = 1.170 + 1.17; log K,,, = -0.530 -2.15).Toutefois le groupe revt-butyle montre des deviations significatives de ces deux droites de corrClations. L'ester non substitut ci-dessus est un inhibiteur reversible de I'hydrolyse enzym a t i q~~e de I'acide 0-hippuryl phenyl-3 L-lactique, et ainsi on n'observe pas d'hydrolyse de cet ester a cause d'une liaison non-reactive. On determine la courbe de p H pour k,,,/K, et kc,, 10: s de I'hydrolyse enzymatique de I'acide 0-(p-nitrobenzoyl) niandelique (pKEH2 = 6.95, PKE" = 7.9 et pKEH2, = 7.5, pKrHs = 8.3) et de l'acide 0-hippuryl phenyl-3 L-lactique (pKEH2 = 5.8, pKEH = 9.3). Pour ce dernier ester, kc,, reste constant pour une variation du p H de 5-10. A la lumiere de ces observations et de la structure connue du cristal de l'enzyme, on discute du mecanisme de I'hydrolyse des esters catalysee par la carboxypeptidase A. On propose une definition des substrats specifiques et non-specifiques pour cette enzyme, basee sur I'observaticn des courbes de p H pour k,,,'K,,,.[Traduit par le journal]During the past few years, evidence has accumulated that the y-carboxyl group of glutamic acid residue 270 plays a role in the mechanism of hydrolyses catalyzed by bovine carboxypeptidase A. Lipscomb and co-workers (1-4), based on their X-ray crystallographic investigation of the structure of this enzyme, originally suggested that this carboxyl...

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