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Synlett 2006(6): 825-830  
DOI: 10.1055/s-2006-939057
LETTER
© Georg Thieme Verlag Stuttgart · New York

A Versatile Strategy for the Synthesis of N-Acetyl-bacillosamine-Containing Disaccharide Building Blocks Related to Bacterial O-Antigens

Emiliano Bedini*, Davide Esposito, Michelangelo Parrilli
Dipartimento di Chimica Organica e Biochimica, Università di Napoli ‘Federico II’, Complesso Universitario Monte Santangelo, Via Cintia 4, 80126 Napoli, Italy
Fax: +39(81)674393; e-Mail: ebedini@unina.it;
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Publication History

Received 27 January 2006
Publication Date:
14 March 2006 (online)

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Abstract

A N-phenyltrifluoroacetimidate glycosyl donor of bacillosamine, a 2,4-diaminosugar contained in several O-antigens from pathogenic bacteria, was synthesized starting from the known peracetylated d-fucal and was demonstrated to be effective for the high-yield coupling to bacillosamine-containing disaccharides. The stereoselectivity of the glycosylations was from moderate to very good depending on the solvent and glycosyl acceptor. The synthetic path was then slightly modified to obtain a similar glycosyl donor with an axial acetyl group on position 4. This building block could be coupled to give a disaccharide, that after five steps (azido reduction, acetylation, O-deacetylation, mesylation, and azide substitution) afforded a bacillosamine-containing disaccharide with differently protected amino functions, in order to provide access to all the currently known structural features of bacillosamine-containing disaccharides known to date contained in natural polysaccharides.

Key words

carbohydrates - O-antigens - aminosugar - bacillos­amine - glycosylation

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Glycosylation Procedure C: A mixture of acceptor (0.044 mmol) and donor (0.057 mmol) was co-evaporated three times with toluene, the residue was then mixed with freshly powdered AW-300 4 Å molecular sieves and suspended under argon in CH2Cl2 (1.0 mL). The mixture was cooled and stirred at 0 °C and a 28 mM solution of TMSOTf in CH2Cl2 (50 µL) was added. After completion of the reaction (TLC analysis), the mixture was neutralized by adding a few drops of Et3N. The mixture was then filtered through a pad of Celite and concentrated to give a residue that was purified by column chromatography. Glycosylation Procedure D: A mixture of acceptor (0.044 mmol) and donor (0.077 mmol) was co-evaporated three times with toluene, the residue was then mixed with freshly powdered AW-300 4 Å molecular sieves and suspended under argon in CH3CN (1.0 mL). The mixture was cooled and stirred at 0 °C and TMSOTf (1.3 µL, 7.7 µmol) was added and the temperature was allowed to rise gradually to r.t. After completion of the reaction (TLC analysis), the mixture was worked up as for Procedure C.

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Compound 8α: [α]D +109.3 (c 1.2, CH2Cl2). 1H NMR (CDCl3, 300 MHz): δ = 7.43-7.33 (m, 10 H, ArH), 6.01 (m, 1 H, CH2CH=CH2), 5.33 (dd, 1 H, J vic = 17.7 Hz, J gem = 1.8 Hz, OCH2CH=CH trans H), 5.25 (dd, 1 H, J vic = 10.2 Hz, J gem = 1.8 Hz, CH2CH=CH cis H), 5.02 (d, 1 H, J 1,2 = 3.6 Hz, H-1B), 4.87 (d, AB, 1 H, J gem = 10.8 Hz, CHHPh), 4.83 (d, AB, 1 H, J gem = 10.8 Hz, CHHPh), 4.79 (d, 1 H, J gem = 11.1 Hz, CHHPh), 4.71 (d, 1 H, J gem = 1.5 Hz, H-1A), 4.61 (d, 1 H, J gem = 11.1 Hz, CHHPh), 4.19 (m, 2 H, CH 2CH=CH2), 4.00 (dd, 1 H, J 3,4 = 9.3 Hz, J 3,2 = 3.0 Hz, H-3A), 3.86 (m, 2 H, H-3B, H-5B), 3.76 (dd, 1 H, J 2,3 = 3.0 Hz, J 2,1 = 1.5 Hz, H-2A), 3.65 (dq, 1 H, J 5,4 = 9.3 Hz, J 5,6 = 6.0 Hz, H-5A), 3.57 (t, 1 H, J 4,5 = J 4,3 = 9.3 Hz, H-4A), 3.36 (dd, 1 H, J 2,3 = 10.5 Hz, J 2,1 = 3.6 Hz, H-2B), 3.33 (s, 3 H, OMe), 3.14 (t, 1 H, J 4,5 = J 4,3 = 9.3 Hz, H-4B), 1.31 (d, 3 H, J 6,5 = 6.0 Hz, H-6A), 1.18 (d, 3 H, J 6,5 = 6.0 Hz, H-6B). 13C NMR (CDCl3, 100 MHz): δ = 138.5, 138.0 (2 C ipso ), 134.7 (CH2 CH=CH2), 128.5-127.9 (ArC), 118.1 (OCH2CH=CH2), 98.4, 93.5 (C-1A, C-1B), 79.6, 78.4, 75.7, 75.3, 74.6, 73.2, 72.1, 68.9, 67.8, 66.6, 63.4 (C-2A, C-2B, C-3A, C-3B, C-4A, C-4B, C-5A, C-5B, CH2Ph, CH2CH=CH2), 54.8 (OMe), 18.3, 18.0 (C-6A, C-6B). ESI-MS: m/z calcd for C30H38N6NaO7 [M + Na]+: 617.27; found: 617.10.
Compound 10α: [α]D +62 (c 0.5, CH2Cl2). 1H NMR (CDCl3, 400 MHz): δ = 7.97-7.25 (m, 15 H, ArH), 5.96 (m, 1 H, CH2CH=CH2), 5.67 (dd, 1 H, J 3,4 = 10.0 Hz, J 3,2 = 3.2 Hz, H-3A), 5.62 (t, 1 H, J 4,3 = J 4,5 = 10.0 Hz, H-4A), 5.38 (dd, 1 H, J vic = 17.2 Hz, J gem = 1.6 Hz, OCH2CH=CH trans H), 5.27 (dd, 1 H, J vic = 10.8 Hz, J gem = 1.6 Hz, CH2CH=CH cis H), 4.99 (d, 1 H, J 1,2 = 1.6 Hz, H-1A), 4.95 (s, 2 H, CH 2 Ph), 4.88 (d, 1 H, J 1,2 = 3.6 Hz, H-1B), 4.30 (m, 2 H, H-2A, CHHCH=CH2), 4.12 (m, 2 H, H-5A, CHHCH=CH2), 3.96 (t, 1 H, J 3,4 = J 3,2 = 9.6 Hz, H-3B), 3.73 (dq, 1 H, J 5,4 = 9.6 Hz, J 5,6 = 6.4 Hz, H-5B), 3.20 (dd, 1 H, J 2,3 = 9.6 Hz, J 2,1 = 3.6 Hz, H-2B), 3.02 (t, 1 H, J 4,3 = J 4,5 = 9.6 Hz, H-4B), 1.34 (d, 3 H, J 6,5 = 6.3 Hz, H-6A), 1.34 (d, 3 H, J 6,5 = 6.4 Hz, H-6B). 13C NMR (CDCl3, 75 MHz): δ = 165.6, 165.5 (2 × COPh), 137.3, 135.0, 133.4, 133.3 (3 × C ipso , CH2 CH=CH2), 129.6-126.3 (ArC), 117.8 (OCH2CH=CH2), 97.1, 96.0 (C-1A, C-1B), 78.7, 76.2, 75.3, 74.3, 71.3, 71.1, 68.5, 68.4, 67.1, 63.1 (C-2A, C-2B, C-3A, C-3B, C-4A, C-4B, C-5A, C-5B, CH2Ph, CH2CH=CH2), 17.5, 17.4 (C-6A, C-6B). ESI-MS: m/z calcd for C36H38N6NaO9: 721.26 [M + Na]+; found: 720.89.
Compound 10β: [α]D +40 (c 0.5, CH2Cl2). 1H NMR (CDCl3, 400 MHz): δ = 8.06-7.34 (m, 15 H, ArH), 5.95 (m, 1 H, CH2CH=CH2), 5.65 (m, 2 H, H-3A, H-4A), 5.37 (dd, 1 H, J vic = 17.2 Hz, J gem = 1.6 Hz, OCH2CH=CH trans H), 5.30 (dd, 1 H, J vic = 10.4 Hz, J gem = 1.6 Hz, CH2CH=CH cis H), 5.05 (d, 1 H, J 1,2 = 1.6 Hz, H-1A), 4.85 (d, 1 H, J gem = 10.8 Hz, CHHPh), 4.73 (d, 1 H, J gem = 10.8 Hz, CHHPh), 4.69 (br s, 1 H, H-2A), 4.33-4.22 (3 H, H-1B, CH 2CH=CH2), 4.08 (dq, 1 H, J 5,4 = 9.6 Hz, J 5,6 = 6.0 Hz, H-5A), 3.51 (t, 1 H, J 3,4 = J 3,2 = 9.6 Hz, H-3B), 3.08 (m, 3 H, H-2B, H-4B, H-5B), 1.32 (d, 3 H, J 6,5 = 6.0 Hz, H-6A), 1.27 (d, 3 H, J 6,5 = 6.0 Hz, H-6B). 13C NMR (CDCl3, 75 MHz): δ = 165.6, 165.4 (2 × COPh), 137.2, 133.5, 133.2, 133.0 (3 × C ipso , CH2 CH=CH2), 129.7-128.4 (ArC), 117.7 (OCH2CH=CH2), 103.1, 98.3 (C-1A, C-1B), 80.9, 76.5, 75.9, 75.3, 71.7, 70.8, 68.2, 67.3, 66.7, 66.5 (C-2A, C-2B, C-3A, C-3B, C-4A, C-4B, C-5A, C-5B, CH2Ph, CH2CH=CH2), 18.4, 17.7 (C-6A, C-6B). ESI-MS: m/z calcd for C36H38N6NaO9 [M + Na]+: 721.26; found: 720.93.
Compound 12α: [α]D +127 (c 0.5, CH2Cl2). 1H NMR (CDCl3, 300 MHz): δ = 7.47-7.30 (m, 5 H, ArH), 5.55 (d, 1 H, J 1,2 = 3.3 Hz, H-1B), 4.86 (app d, 3 H, H-1A, CH 2Ph), 4.28 (dd, 1 H, J 3,4 = 7.2 Hz, J 3,2 = 5.7 Hz, H-3A), 4.11 (d, 1 H, J 2,3 = 5.7 Hz, H-2A), 3.76-3.61 (m, 3 H, H-3B, H-5A, H-5B), 3.49 (dd, 1 H, J 4,5 = 9.9 Hz, J 4,3 = 7.2 Hz, H-4A), 3.37 (m, 4 H, H-2B, OMe), 3.12 (t, 1 H, J 4,3 = J 4,5 = 9.9 Hz, H-4B), 1.53 (s, 3 H, CH3), 1.35 (s, 3 H, CH3), 1.31 (d, 3 H, J 6,5 = 6.0 Hz, H-6B), 1.28 (d, 3 H, J 6,5 = 6.3 Hz, H-6A). 13C NMR (CDCl3, 75 MHz): δ = 137.1 (C ipso ), 128.5-128.1 (ArC), 109.5 [C(CH3)2], 98.0, 95.6 (C-1A, C-1B), 78.3, 78.1, 77.1, 76.1, 75.4, 68.4, 66.9, 63.5, 54.8 (C-2A, C-2B, C-3A, C-3B, C-4A, C-4B, C-5A, C-5B, CH2Ph), 27.9, 26.3 (2 × CH3), 18.3, 18.1 (C-6A, C-6B). ESI-MS: m/z calcd for C23H32N6NaO7
[M + Na]+: 527.22; found: 526.99.
Compound 12β: [α]D +20 (c 0.7, CH2Cl2). 1H NMR (CDCl3, 300 MHz): δ = 7.59-7.22 (m, 5 H, ArH), 4.90-4.79 (m, 3 H, H-1A, CH 2Ph), 4.37 (d, 1 H, J 1,2 = 8.1 Hz, H-1B), 4.22 (dd, 1 H, J 3,4 = 7.2 Hz, J 3,2 = 5.7 Hz, H-3A), 4.12 (d, 1 H, J 2,3 = 5.7 Hz, H-2A), 3.72 (dq, 1 H, J 5,4 = 9.9 Hz, J 5,6 = 6.0 Hz, H-5A), 3.45 (m, 2 H, H-2B, H-4A), 3.37 (s, 3 H, OMe), 3.26 (t, 1 H, J 3,4 = J 3,2 = 9.6 Hz, H-3B), 3.20 (m, 2 H, H-4B, H-5B), 1.52 (s, 3 H, CH3), 1.36 (m, 9 H, H-6A, H-6B, CH3). 13C NMR (CDCl3, 75 MHz): δ = 137.2 (C ipso ), 129.3-128.1 (ArC), 109.4 [C(CH3)2], 101.6, 98.0 (C-1A, C-1B), 82.2, 81.2, 76.0, 75.5, 71.0, 67.5, 66.8, 64.4, 54.9 (C-2A, C-2B, C-3A, C-3B, C-4A, C-4B, C-5A, C-5B, CH2Ph), 28.1, 26.2 (2 CH3), 18.3, 17.7 (C-6A, C-6B). ESI-MS: m/z calcd for C23H32N6NaO7
[M + Na]+: 504.23; found: 527.18.
Compound 14β: [α]D +19 (c 0.7, CH2Cl2). 1H NMR (CDCl3, 300 MHz): δ = 7.41-7.25 (m, 20 H, ArH), 5.86 (m, 1 H, CH2CH=CH2), 5.23 (dd, 1 H, J vic = 17.7 Hz, J gem = 1.8 Hz, OCH2CH=CH trans H), 5.17 (dd, 1 H, J vic = 10.2 Hz, J gem = 1.8 Hz, CH2CH=CH cis H), 4.91 (d, 1 H, J 1,2 = 1.8 Hz, H-1A), 4.82-4.65 (m, 6 H, CHHPh), 4.58 (d, 1 H, J gem = 11.4 Hz, CHHPh), 4.51 (d, 1 H, J gem = 11.7 Hz, CHHPh), 4.31-4.15 (m, 3 H, H-1B, H-4A, CHHCH=CH2), 3.99-3.77 (m, 6 H, H-2A, H-3A, H-5A, H-6A, CHHCH=CH2), 3.23 (t, 1 H, J 2,1 = J 2,3 = 9.3 Hz, H-2B), 3.06 (t, 1 H, J 3,2 = J 3,4 = 9.3 Hz, H-3B), 3.02 (t, 1 H, J 4,3 = J 4,5 = 9.3 Hz, H-4B), 2.89 (dq, 1 H, J 5,4 = 9.3 Hz, J 5,6 = 5.7 Hz, H-5B), 1.16 (d, 3 H, J 6,5 = 5.7 Hz, H-6B). 13C NMR (CDCl3, 100 MHz): δ = 139.1, 138.5, 138.4, 137.6 (4 × C ipso ), 133.8 (CH2 CH=CH2), 129.7-127.0 (ArC), 117.3 (OCH2CH=CH2), 100.9, 97.4 (C-1A, C-1B), 81.6, 78.2, 75.5, 75.4, 75.3, 73.4, 72.8, 72.4, 71.5, 70.5, 68.9, 68.0, 67.8, 67.2 (C-2A, C-2B, C-3A, C-3B, C-4A, C-4B, C-5A, C-5B, C-6A, 4 CH2Ph, CH2CH=CH2), 18.3 (C-6B). ESI-MS: m/z calcd for C43H48N6NaO8 [M + Na]+: 799.34; found: 799.01.

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Compound 16: [α]D +48 (c 0.4, CH2Cl2). 1H NMR (CDCl3, 400 MHz): δ = 7.36-7.26 (m, 10 H, ArH), 6.01 (m, 1 H, CH2CH=CH2), 5.33 (dd, 1 H, J vic = 17.2 Hz, J gem = 1.5 Hz, OCH2CH=CH trans H), 5.25 (dd, 1 H, J vic = 10.3 Hz, J gem = 1.5 Hz, CH2CH=CH cis H), 5.00 (d, 1 H, J 1,2 = 3.3 Hz, H-1B), 4.81 (d, 1 H, J gem = 12.6 Hz, CHHPh), 4.77 (d, 1 H, J gem = 12.6 Hz, CHHPh), 4.75 (d, 1 H, J gem = 11.3 Hz, CHHPh), 4.70 (m, 2 H, H-1A, NH), 4.47 (d, 1 H, J gem = 11.3 Hz, CHHPh), 4.21 (app d, 2 H, CH 2CH=CH2), 4.04 (dd, 1 H, J 3,4 = 9.8 Hz, J 3,2 = 3.2 Hz, H-3A), 3.86-3.71 (m, 3 H, H-2A, H-4A, H-5A), 3.66-3.56 (m, 2 H, H-4B, H-5B), 3.44 (t, 1 H, J 3,4 = J 3,2 = 9.8 Hz, H-3B), 3.37 (m, 4 H, H-2B, OMe), 1.61 (s, 3 H, NAc), 1.37 (d, 3 H, J 6,5 = 6.2 Hz, H-6A), 0.97 (d, 3 H, J 6,5 = 6.2 Hz, H-6B). 13C NMR (CDCl3, 75 MHz): δ = 169.6, 139.5, 137.8, 134.7, 129.7, 125.9 118.2, 98.8, 92.7, 79.3, 76.9, 74.0, 73.3, 73.1, 72.4, 72.2, 67.8, 66.6, 63.1, 54.9, 54.7, 23.3, 17.9, 17.2. ESI-MS: m/z calcd for C32H42N4NaO8 [M + Na]+: 610.30; found: 633.19.