Supporting information

S1 Acyl Group Migration and Cleavage in Selectively Protected -D- Galactopyranosides as Studied by NMR Spectroscopy and Kinetic Calculations Mattias U. Roslund, lli Aitio, Johan Wärnå, Hannu Maaheimo, Dmitry Yu. Murzin, and Reko Leino Supporting information Contents list... S1 General experimental details... S2 Preparative procedures for compounds 113....... S3 Table S1. The chemical shifts for compounds 11c and 4.......... S7 Table S2. The chemical shifts for compounds 22c..........S7 Table S3. The chemical shifts for compounds 33c........S7 Figure S1. Migration for 1 at neutral pd... S8 Figure S2. Migration for 1 at pd = 1........ S8 Figure S3. Initial migration rates for 1 at pd = 1..... S9 Figure S4. Migration for 2 at pd = 8...... S9 Figure S5. Hydrolysis of 2 at pd = 1.... S1 Figure S6. Migration for 2 at pd = 1......... S1 Figure S7. Migration for 3 at pd = 8....... S11 Table S4. Rate constants for the migration products of 13......S12 Table S5. Initial reaction rates for reaction 1for compounds 1 to 3...S12 Figure S8. Calculation of the kinetics for 1 at pd = 8......S13 Figure S9. Calculation of the kinetics for 2 at pd = 8......S14 Figure S1. Calculation of the kinetics for 3 at pd = 8........S15

S2 General: TLC was performed using silica gel F 254 precoated aluminum sheets and visualized by charring with 25 H 2 S 4 in methanol. Column chromatography was performed using silica gel 6 or silica gel 6 enriched with.1 Ca to minimize hydrolysis of acid-labile protecting groups. All operations with air- or moisture-sensitive reagents were conducted under an inert argon atmosphere using standard Schlenk and vacuum techniques. Solvents were dried and distilled under argon prior to use when applicable or purchased as anhydrous from commercial sources. ptical rotations are expressed as [] T D values in deg ml dm1 g 1 units and were measured at 21 ºC using a cell of volume 1 ml and length 9.998 cm. NMR spectra were acquired at 14.1 T using a spectrometer equipped with either a 5 mm normal configuration tunable probe or a 5 mm inverse z-axis fg probe operating at 6.13 MHz for 1 H and 15.92 MHz for 13 C. 1D 1 H spectra were acquired with single-pulse excitation, 45 flip angle, pulse recycle time of 9.5 s and with spectral widths of 7 khz consisting of 64 k data points (digital resolution.11 Hz/pt), zero-filled to 128 or 256 k prior to Fourier transformation. 1D 1 H spectra were processed with a double exponential to effect resolution enhancement prior to spin analysis which was performed using PERCH iteration software 1 for the extraction of H and J H,H. Since the reliable extraction of small couplings approaching the linewidth is heavily dependent on whether they are to a degree resolvable on at least one spin for PERCH NMR software to reliably extract them, only those couplings reliably extracted by PERCH NMR software are reported whilst couplings buried in the linewidth on both interacting spins are not reported (i.e., not extracted) even if their likely presence is probable or is evident from homodecoupling experiments. DQF-CSY, TCSY, and NESY spectra were all acquired in phase-sensitive mode and processed with zero-filling ( 2, 4) and exponential weighting (13 Hz) applied in both dimensions prior to Fourier transformation. 1D 13 C spectra were acquired with single-pulse excitation, 45 flip angle, pulse recycle time of 3.5 s and with spectral widths of 3 khz consisting of 64 k data points (digital resolution.46 Hz/pt), zero-filled to 128256 k and with 1 Hz exponential weighting generally applied prior to Fourier transformation. DEPT 135 were acquired under similar conditions but with a post acquisition delay time of 3 s. HSQC spectra were acquired in phase-sensitive mode and HMBC experiments in magnitude mode and processed with zero-filling ( 2, 4), a 2/3-shifted sinebell function, and exponential weighting (35, 12 Hz) applied in both dimensions prior to Fourier transformation. Both HSQC and HMBC spectra utilized a 1 J C,H coupling of 17 Hz, whilst the HMBC correlations were optimized for a long-range n J C,H coupling of 2 to 8 Hz. For all 2D spectra, the spectral widths and resolution were optimized from the 1D spectra. ph measurements: The EMF (electromotive force) of the glass electrode, measured in an aqueous solution, is usually converted to a ph value by means of suitable buffer solutions with accurately known hydrogen ion activity. The EMF values measured in heavy water could be converted to pd values by means of a similar calibrating procedure assuming the usage of buffer solutions prepared in D 2 from deuterated acids (bases). Because appropriate buffer solutions in heavy water are not straightforward to obtain, the ph meters are usually calibrated in aqueous buffer solutions and used immediately after this calibration for the measurements in heavy water.

S3 In this study the classical formula of pd = ph* +.4 was used to convert the ph meter reading (ph*) into the pd value. 2 Electron impact high-resolution mass spectra (EIMS) were acquired using a direct insert probe scanning from 5 to 15 amu and using electrons energized to 7 ev. Accurate mass measurements were performed using a peak matching technique with PFK as a reference substance at a resolution of 8,1, (at 1 peak height). Experimental procedure for compounds 113: The synthetic preparation of selectively protected compunds for the migration study followed a slightly modified literature procedure. First, benzyl -D-galactopyranoside was prepared from - D-galactose pentaacetate over two steps in 66 yield. 3 The 6--position was protected as silyl ether using TBDPSCl as the silylating agent. Next, the 3- and 4-H groups were protected using the conventional isopropylidene ketal formation (Scheme S1). Finally, the 2-H group was protected as the base labile acetate (Ac), pivaloate (Piv) or benzoate (Bz). The protecting groups in positions 3, 4 and 6 were cleaved using standard conditions after which analytically pure benzyl 2--acetyl--D-galactopyranoside (1) and benzyl 2--benzoyl--D-galactopyranoside (3) were obtained by crystallization from pentane/etac or chloroform. 4 The benzyl 2--pivaloyl- -D-galactopyranoside (2) was purified by column chromatrography (Scheme S2). Scheme S1 Ac Ac Ac Ac Ac H H H TBDPS i ii iii H H Bn H H Bn 5 4 6 TBDPS H Bn 7 i) a) CH 2 Cl 2, BnH, BF 3 Et 2, NEt 3 b) MeH, dioxane, NaMe 66 ii) tert-butyldiphenylchlorosilane, imidazole, DMF, 6 iii) 2,2-dimethoxypropane, ptsh, TEA, 71. Benzyl 6--(tert-butyldiphenylsilyl)-3,4--isopropylidene--D-galactopyranoside (7) was prepared in 28 total yield over 4 steps from 1,2,3,4,6-penta--acetyl--D-galactopyranose. 4 Scheme S2 TBDPS H Bn TBDPS H i ii iii R Bn R Bn H H H R Bn 7 8 R = Ac 9 R = Piv 1 R = Bz 11 R = Ac 12 R = Piv 13 R = Bz 1 R = Ac 2 R = Piv 3 R = Bz i) Ac 2 for 8, PivCl for 9, BzCl for 1 in pyridine, rt, quantitative yield ii) TBAF, THF, rt, 9398 iii) Dowex DR-23 (H + -form), > 9.

S4 Benzyl 2--acetyl--D-galactopyranoside (1) was prepared from benzyl 2--acetyl-6--(tertbutyldiphenylsilyl)-3,4--isopropylidene--D-galactopyranoside (8) via benzyl 2--acetyl-3,4-isopropylidene--D-galactopyranoside (11) according to literature procedure but with improved yields due to longer reaction times. 4 The NMR data were in agreement with those reported previously. 4 Benzyl 6--(tert-butyldiphenylsilyl)-3,4--isopropylidene-2--pivaloyl--D-galactopyranoside (9). To a solution of 7 (21 mg,.38 mmol) in dry pyridine (5 ml) was added pivaloyl chloride (2 µl, 1.63 mmol) and the reaction mixture was stirred overnight at room temperature. Monitoring by TLC (toluene:ethyl acetate 2:1) indicated the formation of one product after 23 hours. The reaction mixture was cooled using an ice-bath and quenched by addition of methanol (2 ml). The solvents were evaporated and the remaining oil extracted with CH 2 Cl 2 (2 ml) and washed with H 2 (2 ml). The organic phase was dried with sodium sulphate and evaporated to dryness. The resulting oil was dried in vacuo to afford pure 9 as an off white solid in quantitative yield: [] 21 D = 9.8 (c =.1 g ml1 in CH 2 Cl 2 ); H (6.13 MHz, CDCl 3, 298 K); 7.757.25 (15H, m, Ph), 5.5 (1H, dd, J = 7.3, 8.2 Hz, H-2), 4.84, 4.59 (2H, d, J = 12.2 Hz, CH 2 Ph), 4.37 (1H, d, J = 8.2 Hz, H-1), 4.25 (1H, dd, J = 2.1, 5.3 Hz, H-4), 4.13 (1H, dd, J = 5.3, 7.3 Hz, H-3), 4.1 (1H, dd, J = 6.6, 1.1 Hz, H-6 b ), 4. (1H, dd, J = 6.5, 1.1 Hz, H-6 a ), 3.87 (1H, ddd, J = 2.1, 6.5, 6.6 Hz, H-5), 1.56, 1.33 (6H, s, C(CH 3 ) 2 ), 1.19 (9H, s, (C(CH 3 ) 3 ), 1.9 (9H, s, (SiC(CH 3 ) 3 ); C (15.92 MHz, CDCl 3, 298 K); 177. (C=), 136.127.7 (Ph), 11.3 (C(CH 3 ) 2 ), 98.8 (C-1), 77.3 (C-3), 73.5 (C-5), 73.4 (C-4), 72.9 (C-2), 69.8 (CH 2 Ph), 62.8 (C-6), 38.7 (C(CH 3 ) 3 ), 27.7, 26.4 (C(CH 3 ) 2 ), 27.1 (C(CH 3 ) 3 ), 26.8 (SiC(CH 3 ) 3 ), 19.2 (SiC(CH 3 ) 3 ); EIMS calculated for C 37 H 48 7 Si [M] + 632.3169, found 632.313. Benzyl 3,4--isopropylidene-2--pivaloyl--D-galactopyranoside (12). To a solution of 9 (212 mg,.33 mmol) in 4 ml THF was added Bu 4 NF 3H 2 (21 mg,.67 mmol) in one portion. The reaction mixture was stirred at ambient temperature. Monitoring by TLC (toluene/ethyl acetate 2 : 1) indicated the formation of one major product. The reaction was quenched after 3 hours by addition of CH 2 Cl 2 (2 ml) and subsequent washing with saturated NaHC 3 (1 ml). The aqueous phase was extracted with an additional portion of CH 2 Cl 2 (1 ml) and the combined organics washed and dried over sodium sulphate. The solvents were evaporated and the remaining off-yellow oil was dried in vacuo to leave the product and the cleaved silyl group as an off-white solid in quantitative yield (132 mg), identified by 1 H and 13 C NMR spectroscopy. [] 21 D = 1.79 (c =.1 g ml1 in CH 2 Cl 2 ); H (6.13 MHz, CDCl 3, 298 K); 7.347.26 (5H, m, Ph), 5.4 (1H, dd, J = 7.1, 8.1 Hz, H-2), 4.85, 4.64 (2H, d, J = 12.2 Hz, CH 2 Ph), 4.42 (1H, d, J = 8.1 Hz, H-1), 4.16 (1H, dd, J = 5.5, 7.1 Hz, H-3), 4.15 (1H, dd, J = 2., 5.5 Hz, H-4), 3.99 (1H, dd, J = 7.5, 11.9 Hz, H-6 a ), 3.84 (1H, dd, J = 4.3, 11.9 Hz, H-6 b ), 3.83 (1H, ddd, J = 2., 4.3, 7.5 Hz, H-5), 1.57, 1.33 (6H, s, C(CH 3 ) 2 ), 1.19 (9H, s, (C(CH 3 ) 3 ); C (15.92 MHz, CDCl 3, 298 K); 177.1 (C=), 137., 128.3, 127.9, (Ph), 11.8 (C(CH 3 ) 2 ), 99.3 (C-1), 77.4 (C-3), 73.9 (C-4), 73.4 (C-5), 72.6 (C-2), 7.6 (CH 2 Ph), 62.4 (C-6), 38.8 (C(CH 3 ) 3 ), 27.7, 26.4 (C(CH 3 ) 2 ), 27.1 (C(CH 3 ) 3 ); EIMS calculated for C 21 H 3 7 [M] + 394.1992, found 394.1985.

S5 Benzyl 2--pivaloyl--D-galactopyranoside (2). 51.8 mg (.13 mmol) of 12 was dissolved in 1 ml dry methanol and 213 mg of Dowex DR-23 was added in one portion. After 23 h the reaction was complete and the solid catalyst was removed by filtration. Solvents were evaporated and the residue was purified by column chromatography to give 46 mg (.13 mmol) pure 2. H (6.13 MHz, CD 3 D, 298 K); 7.327.24 (5H, m, Ph), 5.7 (1H, dd, J = 8., 1. Hz, H-2), 4.87, 4.61 (2H, d, J = 12. Hz, CH 2 Ph), 4.5 (1H, d, J = 8. Hz, H-1), 3.86 (1H, dd, J = 3.4, 1.1 Hz, H-4), 3.82 (1H, dd, J = 7., 11.4 Hz, H-6 b ), 3.76 (1H, dd, J = 5.2, 11.4 Hz, H-6 a ), 3.64 (1H, dd, J = 3.4, 1. Hz, H-3), 3.56 (1H, ddd, J = 1.1, 5.2, 7. Hz, H-5), 1.16 (9H, s, (C(CH 3 ) 3 ); C (15.92 MHz, CD 3 D, 298 K); 179.5 (C=), 138.9, 129.3, 129., 128.7 (Ph), 11.7 (C-1), 76.9 (C-5), 73.6 (C-2), 73.3 (C-3), 71.5 (CH 2 Ph), 7.7 (CH 2 Ph), 7.7 (C-4), 62.3 (C-6), 39.9 (C(CH 3 ) 3 ), 27.6 (C(CH 3 ) 3 ); [] 21 D = 15.2 (c =.4 g ml1 in CH 3 H); EIMS calculated for C 18 H 26 7 [M] + 354.1679, found 354.1649. Benzyl 2--benzoyl-6--(tert-butyldiphenylsilyl)-3,4--isopropylidene--D-galactopyranoside (1). To a solution of 243 mg (.44mmol) of benzyl 6--(tert-butyldiphenylsilyl)- 3,4--isopropylidene--D-galactopyranoside (7) in 5 ml dry pyridine was added 1 µl benzoyl chloride in one portion. The reaction was followed by TLC (toluene: ethyl acetate in a 2:1 ratio) and quenched with 1 ml of methanol after 4h when only the product was observed by TLC. Solvents were removed under reduced pressure and finally dissolved in 2 ml CH 2 Cl 2 and extracted with 2 ml water. The organic phase was dried with Na 2 S 4 and concentrated under reduced pressure to give a white solid in quantitative yield. 1 H and 13 C NMR spectra were aquired in CDCl 3 with TMS and the results were in agreement with those reported previously. 4 Benzyl 2--benzoyl-3,4--isopropylidene--D-galactopyranoside (13). Prepared according to the literature procedure from 1 but with improved yield due to longer reaction time. 4 1 H and 13 C NMR data for 13 have not been reported earlier. H (6.13 MHz, CDCl 3, 298 K); 8.57.15 (1H, m, Ph), 5.32 (1H, dd, J = 7.4, 8.2 Hz, H-2), 4.85, 4.68 (2H, d, J = 12.7 Hz, CH 2 Ph), 4.52 (1H, d, J = 8.2 Hz, H-1), 4.31 (1H, dd, J = 5.4, 7.4 Hz, H-3), 4.2 (1H, dd, J = 2.1, 5.4 Hz, H-3), 4.3 (1H, dd, J = 7.2, 11.5 Hz, H-6 a ), 3.89 (1H, ddd, J = 2.1, 4.2, 7.2 Hz, H-5), 3.88 (1H, dd, J = 4.2, 11.5 Hz, H-6 b ), 1.63, 1.34 (6H, s, C(CH 3 ) 2 ); C (15.92 MHz, CDCl 3, 298 K); 165.4 (C=), 137.127.7 (Ph), 11.9 (C(CH 3 ) 2 ), 99.1 (C-1), 77.3 (C-3), 74. (C-4), 73.5 (C-2), 73.5 (C-5), 7.4 (CH 2 Ph), 62.4 (C-6), 27.7, 26.4 (C(CH 3 ) 2 ). Benzyl 2--benzoyl--D-galactopyranoside (3). Synthesis, NMR, and EIMS analyses of 3 were in agreement with the literature data. 4 Sine the 1 H chemical shifts of 2-Ac, 3-Ac, 4-Ac, 6-Ac (compounds 11c), AcH and benzyl -D-galactopyranoside (4) are remarkably different, their relative populations can be determined in a mixture by simple integration of the 1 H NMR spectra. Details on the chemical shifts are provided in Tables S1S3. In most compounds, the benzyl methylene proton resonances overlap with the water signal. The large downfield shifts (over 1.2 ppm) of the protons attached to the carbon atom (2, 3, 4 or 6) carrying the acylated hydroxyl group is a useful indicator of the position of the ester group. The hydrolysis rates (k 4 ) were normally very small (1.2), except for 3 where it was over 2, and therefore the deviations could be quite large for the small values. The error from the integration of the 1 H NMR spectra can already be several

S6 percent. This accuracy is sometimes sufficient, especially when the compound is known However, the accuracy is usually not adequate for determining the exact number of protons contributing to a given peak, nor is it sufficient for quantitative applications (such as kinetics experiments or assays of product mixtures) where an accuracy of 12 is required. For example, 2 accuracy is not sufficient to decide whether two peaks have a relative ratio of 1:3 or 1:4. btaining 12 accuracy can be achieved but the spectrometer and relaxation factors that also affect the integration must be considered. The integration was here performed with a macro command to integrate the same region in order to minimize the contribution of the human error. First, the migration and cleavage rate of the acetyl group (11c and 4) was monitored by 1 H NMR spectroscopy.

S7 Table S1. Proton chemical shifts for compounds 11c and 4 observed (pd = 8.) in the migration study. 1 1a 1b 1c 4 H1 4.63 4.59 4.55 4.47 4.47 H2 4.93 3.78 3.57 3.56 3.55 H3 3.81 4.83 3.83 n.d. 3.62 H4 3.98 4.11 5.3 3.95 3.92 H5 3.73 n.d. n.d. 3.89 3.68 H6a, H6b 3.78, 3.84 n.d. n.d. 4.254.35 3.76, 3.81 CH 2 Ph 4.71, 4.9 n.d. n.d. n.d. 4.76, 4.96 -Ph 7.377.5 7.377.5 7.377.5 7.377.5 7.397.52 -Ac 2.5 2.17 2.18 2.15 n.d. Table S2. Proton chemical shifts for compounds 22c in pd = 1. observed in the migration study. 2 2a 2b 2c H1 4.7 4.58 4.55 4.47 H2 4.92 3.79 3.59 3.55 H3 3.86 4.81 3.84 3.62 H4 3.97 4.7 5.28 3.95 H5 3.74 n.d. n.d. 3.91 H6a, H6b 3.79, 3.84 n.d. n.d. 4.29, 4.34 CH 2 Ph 4.71, 4.89 n.d. n.d. n.d. -Ph 7.377.5 n.d. n.d. n.d. -Piv 1.44 1.23 1.24 1.1 Table S3. Proton chemical shifts for compounds 33c in pd = 8. observed in the migration study. 3 3a 3b 3c H1 4.78 4.66 4.63 4.45 H2 5.17 3.96 3.73 3.57 H3 4. 5.8 3.94 3.64 H4 4.3 4.24 5.57 4.3 H5 n.d. n.d. n.d. 4.2 H6a, H6b 3.84, 3.89 n.d. n.d. 4.49, 4.64 CH 2 Ph n.d. n.d. n.d. n.d. -Bz n.d. n.d. n.d. n.d.

S8 Migration of the acetyl group as measured with 1 H NMR spectroscopy at 25 C in pd = 6.8 solution and reaction product concentrations are given in Figure S1. 1 8 6 Benzyl 2--acetyl--D-galactopyranoside (1) Benzyl 3--acetyl--D-galactopyranoside (1a) Benzyl 4--acetyl--D-galactopyranoside (1b) Benzyl 6--acetyl--D-galactopyranoside (1c) Benzyl -D-galactopyranoside (4) 4 2 2 4 6 8 1 12 Time / h Figure S1. Migration at neutral pd (6.8) The migration was followed by 1 H NMR for 55 days and was fast in the beginning before the acetyl grpup was hydrolyzed to form AcH, neutralizing the solution with already 1 AcH from the hydrolyzed galactose moiety (Figure S2). 1 8 6 Benzyl 2--acetyl--D-galactopyranoside (1) Benzyl 3--acetyl--D-galactopyranoside (1a) Benzyl 4--acetyl--D-galactopyranoside (1b) Benzyl 6--acetyl--D-galactopyranoside (1c) Benzyl -D-galactopyranoside (4) 4 2 1 2 3 4 5 Time / h Figure S2. Migration of Ac at pd 1. (unbuffered solution)

S9 In the expansion of the first four hours of the migration at pd 1. it is clearly shown that already very low contrations of AcH (.2 after 2 min) dramatically change the ph and so the migration rates. 1 8 6 Benzyl 2--acetyl--D-galactopyranoside (1) Benzyl 3--acetyl--D-galactopyranoside (1a) Benzyl 4--acetyl--D-galactopyranoside (1b) Benzyl 6--acetyl--D-galactopyranoside (1c) Benzyl -D-galactopyranoside (4) 4 2,,5 1, 1,5 2, 2,5 3, 3,5 4, Time / h Figure S3. Expansion of the initial migration rates of Ac in pd 1.. In Figure S4 the migration rates determined for benzyl 2--pivaloyl--D-galactopyranoside (22c) are presented. 1 9 8 7 6 2 Benzyl 2--pivaloyl--D-galactopyranoside (2) Benzyl 3--pivaloyl--D-galactopyranoside (2a) Benzyl 4--pivaloyl--D-galactopyranoside (2b) Benzyl 6--pivaloyl--D-galactopyranoside (2c) 1 1 2 3 4 Time / h Figure S4. Migration of pivaloyl group in compounds 22c (hydrolysis was not observed) at pd 8. and 25 C in buffered D 2 (1 mm Na-phosphate buffer).

S1 In Figure S5 the cleavage rate of the pivaloyl at low ph* =.6 (pd = 1.) is illustrated. 1 98 96 4 Benzyl 2--pivaloyl--D-galactopyranoside (2) Benzyl -D-galactopyranoside (4) 2 4 8 12 16 Time / h Figure S5. The cleavage of the Piv group at low ph is much slower than the hydrolysis of the acetyl group. The migration was very slow for the large pivaloyl group, approximately 251 times slower as could be proved by the 1 H NMR measurements and detailed investigation of the reaction rates. The NMR measurements were stopped after 2 days. Figure S6 shows the migration rates for benzyl 2--pivaloyl--D-galactopyranose (2) at pd 1.. 1 8 6 Benzyl 2--pivaloyl--D-galactopyranoside (2) Benzyl 3--pivaloyl--D-galactopyranoside (2a) Benzyl 4--pivaloyl--D-galactopyranoside (2b) Benzyl 6--pivaloyl--D-galactopyranoside (2c) Benzyl -D-galactopyranoside (4) 4 2 1 2 3 4 5 Time / h Figure S6. Slow migration of the bulky pivaloyl group at pd 1. and when finally hydrolysed the ph of the solution changed to more neutral and the migration slowed down.

S11 The migration rates for both the acetyl (Figure 2) and benzoyl group (Figure S7) were relatively fast at pd = 8. while the bulkier pivaloyl migrated much slower (Figure S4). At higher pd (1.) the benzoyl migration was too fast for the 1 H NMR analyses, while the acetyl and pivaloyl migrations could still be followed (Figures S2 and S6). 1 8 6 Benzyl 2--benzoyl--D-galactopyranoside (3) Benzyl 3--benzoyl--D-galactopyranoside (3a) Benzyl 4--benzoyl--D-galactopyranoside (3b) Benzyl 6--benzoyl--D-galactopyranoside (3c) Benzyl -D-galactopyranoside (4) 4 2 1 2 3 4 5 Time / h Figure S7. The benzoyl group migration at pd = 8. for 3.

S12 The rate constants listed in Tables S4 and S5 show the initial rates of reaction 1 and initial concentrations of reactant 1. The reaction is fastest for the acetyl group migration and slowest for the pivonyl group migration. Reaction 1 is fastest for migration of the acetyl groups and slowest for migration of the pivaloyl groups. Table S4. Rate constants for the migration products of 13. h 1 1 2 3 k 1 k 1 k 2 k 2 k 3 k 3 k 4 852 ± 5.6 459 ± 11.8 359 ± 76 2177 ± 8 18 ± 25 431 ± 1.4 7.4 ±.8 13.7 ±.9 19.9 ± 9. 143 ± 27 6 ± 2 3.7 ± 13.8 n.d. n.d. 1376 ± 148 14578 ± 1126 66755 ± 652 3669 ± 52 6764 ± 51 5458 ± 384 n.d. parameters not determined due to low concentration levels of C4 and C6 ester protected components. Table S5. Initial concentrations and reaction rates for reaction 1 for compounds 1 to 3. r 1 c 1,initial 1 Acetyl 9.82 mol/l h 11.5 1 3 mol/l 2 Benzoyl 5.86 mol/l h.534 1 3 mol/l 3 Pivaloyl.12 mol/l h 8.547 1 3 mol/l

S13 Figure S8. Fit of the model to the experimental data for the acetyl group migration at pd = 8.. 1 9 8 7 6 5 4 3 2 1 5 1 15 2 25 3 35 4 45 5 Time (h) (o) Benzyl 2--acetyl--D-galactopyranoside (1) () Benzyl 3--acetyl--D-galactopyranoside (1a) () Benzyl 4--acetyl--D-galactopyranoside (1b) (*) Benzyl 6--acetyl--D-galactopyranoside (1c) () Benzyl -D-galactopyranoside (4)

S14 Figure S9. Fit of the model to the experimental data for the slow migration for the pivaloyl group at pd = 8.. 1 9 8 7 6 5 4 3 2 1 5 1 15 2 25 3 35 4 45 5 Time (h) (o) Benzyl 2--pivaloyl--D-galactopyranoside (2) () Benzyl 3--pivaloyl--D-galactopyranoside (2a) () Benzyl 4--pivaloyl--D-galactopyranoside (2b) (*) Benzyl 6--pivaloyl--D-galactopyranoside (2c) () Benzyl -D-galactopyranoside (4)

S15 Figure S1. Fit of the model to the experimental data for the benzoyl migration at pd = 8.. 1 9 8 7 6 5 4 3 2 1 1 2 3 4 5 6 Time (h) (o) Benzyl 2--benzoyl--D-galactopyranoside (3) () Benzyl 3--benzoyl--D-galactopyranoside (3a) () Benzyl 4--benzoyl--D-galactopyranoside (3b) (*) Benzyl 6--benzoyl--D-galactopyranoside (3c) () Benzyl -D-galactopyranoside (4) References: 1. Laatikainen, R.; Niemitz, M.; Weber, U.; Sundelin, J.; Hassinen, T.; Vepsäläinen, J. J. Magn. Reson., Ser. A 1996, 12, 11. 2. Bastardo, L. A.; Mészáros, R.; Varga, I.; Gilányi, T.; Cleasson, P. M. J. Phys. Chem. B 25, 19, 161961622. 3. Clausen, M. H.; Jørgensen, M. R.; Thorsen, J.; Madsen, R. J. Chem. Soc., Perkin Trans. 1 21, 543551. 4. Lehtilä, R. L.; Lehtilä, J..; Roslund, M. U.; Leino, R. Tetrahedron 24, 6, 3653 3661.