Observations on the Regioselectivity of Glycosylation of Mannose and Glucose: Selective Glycosylation of the Secondary 4-Hydroxyl of 4,6-Diol Acceptors

Thomas W. D. F. Rising; Christoph D. Heidecke; Antony J. Fairbanks

doi:10.1055/s-2007-980355

LETTER

Observations on the Regioselectivity of Glycosylation of Mannose and Glucose: Selective Glycosylation of the Secondary 4-Hydroxyl of 4,6-Diol Acceptors

Thomas W. D. F. Rising, Christoph D. Heidecke, Antony J. Fairbanks*
Chemistry Research Laboratory, Oxford University, Mansfield Road, Oxford, OX1 3TA, UK
Fax: +44(1865)275647; e-Mail: antony.fairbanks@chem.ox.ac.uk;

Abstract

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Abstract

The regioselectivity of glycosylation of manno and gluco acceptor diols possessing free hydroxyl groups at the 4- and 6-positions is found to be strongly dependent on functionalization of the 3-hydroxyl group. Surprisingly, highly regioselective glycosylation of the more hindered 4-hydroxyl can be readily achieved in the presence of the primary 6-hydroxyl in cases where the 3-hydroxyl of the acceptor is protected as a benzyl ether and when the donor possesses an ester participating group at the 2-position. However, reverse regioselectivity, namely glycosylation of the 6-hydroxyl, is observed when the 3-hydroxyl has been previously glycosylated.

Key words

carbohydrates - regioselectivity - glycosylations - N-glycans - mannose

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References

References and Notes

<A NAME="RD07407ST-1A">1a</A> Varki A. Glycobiology 1993, 3: 97

<A NAME="RD07407ST-1B">1b</A> Dwek RA. Chem. Rev. 1996, 96: 683

For some leading references, see:

<A NAME="RD07407ST-2A">2a</A> Matsuo I. Wada M. Manabe S. Yamaguchi Y. Otake K. Kato K. Ito Y. J. Am. Chem. Soc. 2003, 125: 3402

<A NAME="RD07407ST-2B">2b</A> Wu B. Hua Z. Warren JD. Ranganathan K. Wan Q. Chen G. Tan Z. Chen J. Endo A. Danishefsky SJ. Tetrahedron Lett. 2006, 47: 5577

<A NAME="RD07407ST-2C">2c</A> Wu X. Grathwohl M. Schmidt RR. Angew. Chem. Int. Ed. 2002, 41: 4489

<A NAME="RD07407ST-2D">2d</A> Du Y. Zhang M. Kong F. Tetrahedron 2001, 57: 1757

<A NAME="RD07407ST-2E">2e</A> Chiesa MV. Schmidt RR. Eur. J. Org. Chem. 2000, 3541

<A NAME="RD07407ST-2F">2f</A> Paulsen H. Angew. Chem., Int. Ed. Engl. 1990, 29: 823

<A NAME="RD07407ST-3">3</A> Schachter H. In Carbohydrates in Chemistry and Biology Vol. 3: Ernst B. Hart GW. Sinaӱ P. Wiley-VCH; Weinheim: 2000. p.155

<A NAME="RD07407ST-4A">4a</A> Schuberth R. Unverzagt C. Tetrahedron Lett. 2005, 46: 4210

<A NAME="RD07407ST-4B">4b</A> Weiss H. Unverzagt C. Angew. Chem. Int. Ed. 2003, 42: 4261

<A NAME="RD07407ST-4C">4c</A> Unverzagt C. Angew. Chem., Int. Ed. Engl. 1997, 36: 1989

<A NAME="RD07407ST-5">5</A> Rising TWDF. Claridge TDW. Moir JWB. Fairbanks AJ. ChemBioChem 2006, 7: 1177

<A NAME="RD07407ST-6">6</A> Rising TWDF. Claridge TDW. Davies N. Gamblin DP. Moir JWB. Fairbanks AJ. Carbohydr. Res. 2006, 341: 1574

<A NAME="RD07407ST-7A">7a</A> Jiang L. Chan T.-H. Tetrahedron Lett. 1998, 39: 355

<A NAME="RD07407ST-7B">7b</A> Okawa M. Liu WC. Nakai Y. Koshida S. Fukase K. Kusumoto S. Synlett 1996, 1179

<A NAME="RD07407ST-7C">7c</A> Garegg PJ. Pure Appl. Chem. 1984, 56: 845

<A NAME="RD07407ST-7D">7d</A> Lipták A. Imre J. Harangi J. Nánási P. Neszmélyi A. Tetrahedron 1982, 38: 3721

<A NAME="RD07407ST-7E">7e</A> Bhattacharjee SS. Gorin PAJ. Can. J. Chem. 1969, 47: 1195

<A NAME="RD07407ST-8">8</A> For a recent review of some reciprocal donor/acceptor selectivity which may control the regiochemistry of glycosylation of different secondary hydroxyl groups, see: Fraser-Reid B. López JC. Gómez AM. Uriel C. Eur. J. Org. Chem. 2004, 1387

For some recent examples, see:

<A NAME="RD07407ST-9A">9a</A> López JC. Agocs A. Uriel C. Gómez AM. Fraser-Reid B. Chem. Commun. 2005, 5088

<A NAME="RD07407ST-9B">9b</A> Chou C.-H. Wu C.-S. Chen C.-H. Lu L.-D. Kulkarni SS. Wong C.-H. Hung S.-C. Org. Lett. 2003, 4: 585

<A NAME="RD07407ST-9C">9c</A> Zeng Y. Kong F. Carbohydr. Res. 2003, 338: 843

<A NAME="RD07407ST-10">10</A> Wuts PGM. Greene TW. Protective Groups in Organic Synthesis 4th ed: Wiley; New York: 2007.

<A NAME="RD07407ST-11A">11a</A> Watt GM. Boons G.-J. Carbohydr. Res. 2004, 339: 181

<A NAME="RD07407ST-11B">11b</A> Smiljanic N. Halila S. Moreau V. Djedaïni-Pilard F. Tetrahedron Lett. 2003, 44: 8999

<A NAME="RD07407ST-11C">11c</A> Wang W. Kong F. J. Org. Chem. 1999, 64: 5091

<A NAME="RD07407ST-11D">11d</A> Boons GJ. Zhu T. Synlett 1997, 809

Typical Glycosylation Procedure
Diol glycosyl acceptor (˜40 mg) and trichloroacetimidate glycosyl donor (˜30 mg, 1.1 equiv) were dissolved in dry CH₂Cl₂ (˜5 mL) and transferred via canula to a flame-dried round-bottomed flask containing activated 4 Å MS (10 mg). The solution was cooled to -60 °C and stirred under an atmosphere of argon. TMSOTf (0.05 equiv) was added. The reaction mixture was stirred under argon, and allowed to warm to r.t. slowly. After 15 h, TLC (typically PE-EtOAc, 1:1) indicated formation of a major product (typically R _f = 0.25) and complete consumption of trichloroacetimidate donor (typically R _f = 0.5). Then, Et₃N (10 µL) was added and the solution stirred for a further 10 min. The reaction mixture was then filtered through Celite^® and the filtrate concentrated in vacuo. The residue was then purified by flash column chromatography (typically eluting with PE-EtOAc, 1:1) to give the α(1→4)-linked trisaccharide product as a white foam.

Selected data for 7: white foam; [α]_D ²⁴ +38 (c 1.0, CHCl₃). IR (KBr disc): ν_max = 3473 (br, OH), 1777, 1744, 1715 (s, C=O) cm^-1. ¹H NMR (500 MHz, CDCl₃): δ = 2.05, 2.13 [6 H, 2 × s, OC(O)CH₃], 3.14 (1 H, ddd, J _4b,5b = 9.5 Hz, J _5b,6b = 5.4 Hz, J _5b,6 _′b 2.2 Hz, H-5b), 3.38 (1 H, dd, J _2b,3b = 3.1 Hz, J _3b,4b = 9.3 Hz, H-3b), 3.54 (1 H, dd, J _6b,6 _′b 12.1 Hz, H-6b), 3.63-3.76 (9 H, m, H-4c, H-5a, H-5c, H-6c, H-6′b, H-6′c, OCH₃), 3.79 (1 H, dd, J _5a,6a = 2.0 Hz, J _6a, ₆ _′a = 11.4 Hz, H-6a), 3.82-3.85 (1 H, m, H-3c, H-6′a), 3.90 (1 H, app t, J = 9.4 Hz, H-4b), 4.16 (1 H, app t, J = 9.2 Hz, H-4a), 4.31, 4.59 (2 H, ABq, J = 10.8 Hz, PhCH₂), 4.33 (1 H, dd, J _2a,3a = 10.7 Hz, J _3a,4a = 8.5 Hz, H-3a), 4.39 (1 H, dd, J _1a,2a = 8.4 Hz, H-2a), 4.43, 4.81 (2 H, ABq, J = 10.9 Hz, PhCH₂), 4.46, 4.89 (2 H, ABq, J = 12.4 Hz, PhCH₂), 4.49, 4.77 (2 H, ABq, J = 12.1 Hz, PhCH₂), 4.51, 4.75 (2 H, ABq, J = 11.0 Hz, PhCH₂), 4.52, 4.61 (2 H, ABq, J = 12.3 Hz, PhCH₂), 4.67 (1 H, s, H-1b), 5.33 (1 H, d, J _1c,2c = 1.6 Hz, H-1c), 5.47-5.485 (2 H, m, H-2b, H-2c), 5.61 (1 H, d, H-1a), 6.69-6.72 (2 H, m, 2 × Ar-H), 6.79-6.82 (2 H, m, 2 × Ar-H), 6.85-6.91 (3 H, m, 3 × ArH), 7.01-7.03 (2 H, m, 2 × ArH), 7.13-7.14 (2 H, m, 2 × ArH), 7.21-7.36 (23 H, m, 23 × ArH), 7.61-7.85 (4 H, m, 4 × ArH). ¹³C NMR (125.8 MHz, CDCl₃): δ = 21.0, 21.0 [2 × q, 2 × OC(O)CH₃], 55.6 (q, OCH₃), 55.6 (d, C-2a), 61.8 (t, C-6b), 67.5 (d, C-2b), 68.3 (t, C-6a), 68.5 (d, C-2c), 68.7 (t, C-6c), 71.1 (t, PhCH₂), 71.6 (d, C-4b), 71.8 (t, PhCH₂), 72.4 (d, C-5c), 73.4, 73.5 (2 × t, 2 × PhCH₂), 74.0 (d, C-4c), 74.5 (d, C-5a), 74.8 (t, PhCH₂), 75.0 (d, C-5b), 75.1 (t, PhCH₂), 76.9 (d, C-3a), 78.2 (d, C-3c), 78.6 (d, C-4a), 80.2 (d, C-3b), 97.6 (d, C-1a), 98.5 (d, C-1b), 99.2 (d, C-1c), 114.3, 118.6, 123.3, 127.3, 127.6, 127.6, 127.7, 127.8, 127.9, 127.9, 128.0, 128.1, 128.3, 128.4, 128.4, 128.5, 128.6 (17 × d, 36 × ArC), 131.5 (s, 2 × ArC), 133.8 (d, 2 × ArC), 136.9, 137.9, 137.9, 137.9, 138.2, 138.2, 150.8, 155.4 (8 × s, 8 × ArC), 169.9, 170.3 (2 × s, 4 × C=O); J _C-1a/H-1a = 166 Hz (β), J _C-1b/H-1b = 160 Hz (β), J _C-1c/H-1c = 176 Hz (α). MS (ESI⁺) [M + MeCN/NH₄ ⁺](major), [M + Na⁺]: m/z calcd (%) = 1386.5 (100), 1387.6 (88), 1388.6 (42), 1389.6 (14), 1390.6 (4) [M + Na⁺]; found: 1386.5 (100), 1387.6 (83), 1388.6 (32), 1389.6 (8), 1390.6 (2).

In all cases the regiochemistry of the newly formed anomeric linkage was identified by a combination of 2D NMR experiments including COSY, HSQC, HSQC ‘non-decoupled’, HSQC-TOCSY, TOCSY, HMBC, and DEPT.

<A NAME="RD07407ST-15">15</A> For examples of the regioselective glycosylation of secondary carbohydrate trityl ethers in the presence of primary ones, see: Tsvetkov YE. Kitov PI. Backinowsky LV. Kochetkov NK. Tetrahedron Lett. 1993, 34: 7977

Selected data for 9: white foam; [α]_D ²⁴ +44 (c 1.0, CHCl₃). IR (KBr disc): ν_max = 3477 (br, OH), 1776, 1747, 1716 (s, C=O) cm^-1. ¹H NMR (500 MHz, CDCl₃): δ = 2.00, 2.17 [6 H, 2 × s, C(O)CH₃], 2.19-2.25, 2.42-2.49 [2 H, 2 × m, OC(O)CH₂CH₂], 2.54-2.60, 2.72-2.79 [2 H, 2 × m, OC(O)CH₂CH₂], 3.20 (1 H, ddd, J _4b,5b = 9.4 Hz, J _5b,6b = 5.2 Hz, J _5b,6 _′b = 2.0 Hz, H-5b), 3.52 (1 H, dd, J _6b,6 _′b = 12.5 Hz, H-6b), 3.53 (1 H, app t, J = 9.1 Hz, H-3b), 3.64-3.69 (3 H, m, H-5a, H-6c, H-6′c), 3.71 (3 H, s, OCH₃), 3.73-3.78 (3 H, m, H-4c, H-5c, H-6′b), 3.81-3.86 (3 H, m, H-3c, H-4b, H-6a), 3.89 (1 H, dd, J _5a,6 _′a = 3.1 Hz, J _6a,6 _′a = 11.2 Hz, H-6′a), 4.09 (1 H, app t, J = 9.2 Hz, H-4a), 4.30 (1 H, dd, J _2a,3a = 10.7 Hz, J _3a,4a = 8.6 Hz, H-3a), 4.38 (1 H, dd, J _1a,2a = 8.4 Hz, H-2a), 4.44-4.46 (2 H, m, 2 × PhCH), 4.48, 4.60 (2 H, ABq, J = 12.2 Hz, PhCH₂), 4.50-4.53 (1 H, m, H-1b), 4.52, 4.71 (2 H, ABq, J = 11.0 Hz, PhCH₂), 4.52, 4.81 (2 H, ABq, J = 11.6 Hz, PhCH₂), 4.61, 4.73 (2 H, ABq, J = 11.4 Hz, PhCH₂), 4.83 (2 H, m, 2 × PhCH), 5.00 (1 H, dd, J _1b,2b = 8.5 Hz, J _2b,3b = 9.2 Hz, H-2b), 5.30 (1 H, d, J _1c,2c = 1.5 Hz, H-1c), 5.45 (1 H, dd, J _2c,3c = 2.8 Hz, H-2c), 5.61 (1 H, d, H-1a), 6.67-6.71 (2 H, m, 2 × ArH), 6.80-6.88 (5 H, m, 5 × Ar-H), 7.02-7.04 (2 H, m, 2 × Ar-H), 7.14-7.16 (2 H, m, 2 × ArH), 7.21-7.40 (23 H, m, 23 × ArH), 7.59-7.87 (4 H, m, 4 × ArH). ¹³C NMR (125.8 MHz, CDCl₃): δ = 20.9 [q, OC(O)CH₃], 27.7 [t, OC(O)CH₂CH₂], 29.8 [q, CC(O)CH₃], 37.6 [t, OC(O)CH₂CH₂], 55.6 (q, OCH₃), 55.6 (d, C-2a), 61.6 (t, C-6b), 67.6 (t, C-6a), 68.7 (t, C-6c), 68.7 (d, C-2c), 71.9 (t, PhCH₂), 72.5 (d, C-5c), 73.5, 73.6 (2 × t, 2 × PhCH₂), 73.8 (d, C-2b), 74.0 (d, C-4c), 74.5 (d, C-4b), 74.5 (t, PhCH₂), 74.8 (d, C-5b), 74.9 (d, C-5a), 74.9, 75.1 (2 × t, 2 × PhCH₂), 76.8 (d, C-3a), 78.1 (2 × d, C-3c, C-4a), 83.6 (d, C-3b), 97.5 (d, C-1a), 98.9 (d, C-1c), 100.2 (d, C-1b), 114.3, 118.7, 123.3, 127.1, 127.1, 127.4, 127.7, 127.7, 127.8, 127.9, 127.9, 127.9, 127.9, 128.0, 128.2, 128.3, 128.3, 128.4, 128.5 (19 × d, 36 × ArC), 131.6 (s, 2 × ArC), 133.7 (d, 2 × ArC), 137.8, 137.8, 137.9, 138.0, 138.1, 138.3, 150.8, 155.3 (8 × s, 8 × ArC), 170.0, 171.2, 206.1 (3 × s, 5 × C=O); J _C-1a/H-1a = 166 Hz (β), J _C-1b/H-1b = 163 Hz (β), J _C-1c/H-1c = 176 Hz (α). MS (ESI⁺) [M + MeCN/NH₄ ⁺](major), [M + Na⁺]: m/z calcd (%) = 1442.6 (100), 1443.6 (91), 1444.6 (45), 1445.6 (16), 1446.6 (5) [M + Na⁺]; found: 1442.6 (100), 1443.6 (90), 1444.6 (37), 1445.6 (9), 1446.6 (2).

Selected data for 11: white foam; [α]_D ¹⁹ +16 (c 1.0, CHCl₃). IR (KBr disc): ν_max = 3445 (br, OH), 1777, 1717 (s, C=O) cm^-1. ¹H NMR (500 MHz, CDCl₃): δ = 2.17 [3 H, s, C(O)CH₃], 2.18-2.24, 2.42-2.48 [2 H, 2 × m, OC(O)CH₂CH₂], 2.54-2.60, 2.72-2.79 [2 H, 2 × m, OC(O)CH₂CH₂], 3.22 (1 H, ddd, J _4b,5b = 9.5 Hz, J _5b,6b = 5.5 Hz, J _5b,6 _′b = 2.1 Hz, H-5b), 3.52 (1 H, dd, J _6b,6 _′b = 12.2 Hz, H-6b), 3.55 (1 H, app t, J = 9.1 Hz, H-3b), 3.66-3.85 (10 H, m, H-4b, H-5a, H-5c, H-6a, H-6c, H-6′b, H-6′c, OCH₃), 3.89 (1 H, dd, J _5a,6 _′a = 3.3 Hz, J _6a,6 _′a = 11.1 Hz, H-6′a), 3.95 (1 H, app t, J = 9.2 Hz, H-4c), 3.99 (1 H, dd, J _2c,3c = 2.8 Hz, J _3c,4c = 9.2 Hz, H-3c), 4.09 (1 H, app t, J = 8.9 Hz, H-4a), 4.30 (1 H, dd, J _2a,3a = 10.7 Hz, J _3a,4a = 8.5 Hz, H-3a), 4.39 (1 H, dd, J _1a,2a = 8.5 Hz, H-2a), 4.44 (1 H, d, J = 12.4 Hz, PhCH), 4.49-4.53 (4 H, m, H-1b, 3 × PhCH), 4.57 (1 H, d, J = 11.4 Hz, PhCH), 4.60 (1 H, d, J = 11.3 Hz, PhCH), 4.66 (1 H, d, J = 12.1 Hz, PhCH), 4.78 (1 H, d, J = 12.7 Hz, PhCH), 4.80-4.84 (4 H, m, 4 × PhCH), 4.98 (1 H, dd, J _1b,2b = 8.2 Hz, J _2b,3b = 9.4 Hz, H-2b), 5.42 (1 H, d, J _1c,2c = 1.7 Hz, H-1c), 5.61 (1 H, d, H-1a), 5.68 (1 H, app t, J = 2.3 Hz, H-2c), 6.69-6.71 (2 H, m, 2 × ArH), 6.81-6.89 (4 H, m, 4 × ArH), 7.02-7.39 (30 H, m, 30 × ArH), 7.53-7.83 (5 H, m, 5 × ArH), 7.96-7.98 (2 H, m, 2 × ArH). ¹³C NMR (125.8 MHz, CDCl₃): δ = 27.7 [t, OC(O)CH₂CH₂], 29.9 [q, CC(O)CH₃], 37.7 [t, OC(O)CH₂CH₂], 55.6 (q, OCH₃), 55.6 (d, C-2a), 61.8 (t, C-6b), 67.6 (t, C-6a), 68.9 (t, C-6c), 69.1 (b, C-2c), 71.7 (t, PhCH₂), 72.8 (d, C-5c), 73.5, 73.6 (2 × t, 2 × PhCH₂), 73.9 (d, C-2b), 74.1 (d, C-4c), 74.7 (t, PhCH₂), 74.8 (d, C-4b), 74.9 (2 × d, C-5a, C-5b), 74.9, 75.2 (2 × d, 2 × PhCH₂), 76.8 (d, C-3a), 78.1 (2 × d, C-3c, C-4a), 83.5 (d, C-3b), 97.5 (d, C-1a), 98.9 (d, C-1c), 100.2 (d, C-1b), 114.3, 118.7, 123.3, 127.2, 127.3, 127.4, 127.5, 127.6, 127.7, 127.8, 127.9, 128.0, 128.0, 128.2, 128.3, 128.3, 128.6, 129.9 (18 × d, 41 × ArC), 131.5 (s, 2 × ArC), 133.1, 133.7 (2 × d, 2 × ArC), 137.7, 137.9, 138.0, 138.1, 138.2, 138.3, 150.9, 155.3 (8 × s, 9 × ArC), 165.3, 171.2, 206.1 (3 × s, 5 × C=O); J _C-1a/H-1a = 165 Hz (β), J _C-1b/H-1b = 164 Hz (β), J _C-1c/H-1c = 175 Hz (α). MS (ESI⁺) [M + MeCN/NH₄ ⁺](major), [M + Na⁺]: m/z calcd (%) = 1504.6 (100), 1505.6 (96), 1506.6 (50), 1507.6 (19), 1508.6 (5) [M + Na⁺]; found: 1504.6 (100), 1505.6 (94), 1506.6 (41), 1507.6 (12), 1508.6 (3).

<A NAME="RD07407ST-18">18</A> Paulsen H. Angew. Chem., Int. Ed. Engl. 1982, 21: 155

<A NAME="RD07407ST-19A">19a</A> Cid MB. Valverde S. López JC. Gómez AM. García M. Synlett 2005, 1095

<A NAME="RD07407ST-19B">19b</A> Cid MB. Alfonso F. Martín-Lomas M. Synlett 2005, 2052

<A NAME="RD07407ST-19D">19d</A> Sinaӱ P. Pure Appl. Chem. 1978, 50: 1437

<A NAME="RD07407ST-20">20</A> For a recent review of the uses and intermediacy of sugar orthoesters, see: Kong F. Carbohydr. Res. 2007, 342: 345

<A NAME="RD07407ST-21">21</A> Mootoo DR. Konradsson P. Udodong U. Fraser-Reid B. J. Am. Chem. Soc. 1988, 110: 5583

<A NAME="RD07407ST-22A">22a</A> Fraser-Reid B. López JC. Radhakrishnan KV. Mach M. Schlueter U. Gómez AM. Uriel C. Can. J. Chem. 2002, 124: 1075

<A NAME="RD07407ST-22B">22b</A> Fraser-Reid B. Anilkumar GN. Nair LG. Radhakrishnan KV. López JC. Gómez A. Uriel C. Aust. J. Chem. 2002, 55: 123

<A NAME="RD07407ST-22C">22c</A> López JC. Gómez A. Fraser-Reid B. Uriel C. Tetrahedron Lett. 2003, 44: 1417