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Synlett 2003(9): 1319-1322
DOI: 10.1055/s-2003-40350
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Orthoester-Based Strategy for Efficient Synthesis of the Virulent Antigenic-1,2-Linked Oligomannans of Candida albicans

Felix Mathewa, Mateusz Macha, Kevin C. Hazenb, Bert Fraser-Reid*a
a Natural Products and Glycotechnology Research Institute, Inc. (NPG), 4118 Swarthmore Road, Durham, NC 27707, USA
Fax: +1(919)4936113; e-Mail: Dglucose@aol.com;
b Departments of Pathology and Microbiology, University of Virginia Health System, Charlottesville, VA 22908, USA
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Publication History

Received 10 May 2003
Publication Date:
30 June 2003 (online)

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Abstract

Orthobenzoates of glucose and mannose provide donor and acceptor partners to produce a disaccharide bearing a benzoyl group at the site where gluco to manno conversion is required, the inverted center being ready to function, iteratively, as the next acceptor for the gluco n-pentenyl orthobenzoate to extend the oligomannan.

Key words

n-pentenylorthoesters - β-oligomannosides - iterative synthesis - structure verification

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Typical procedure for preparation of 9 by reaction of 15a with 1: The acceptor, trisaccharide 15a (n = 1, 1.40 g, 1 mmol) and the donor (1, 4.36 g, 7 mmol) were separately rotovaporised twice with dry toluene, and then dried for 8 h under vacuum (0.5 mm Hg). To a solution of the acceptor in 15 mL of dry CH2Cl2 were added freshly activated molecular sieves (4 g, 3 A beads, 8-12 mesh), NIS re-crystallized from hot CH2Cl2 and cold hexane and dried under vacuum (0.5 mm Hg, over night, 1.35 g, 6 mmol) followed by TBDMSOTf (0.1 mL, 0.4 mmol) at 10 ºC (ice bath). To this solution was added a solution of NPOE in CH2Cl2 drop-wise over 10 min, and then the ice bath was removed. After 10 min TLC (7:3, hexane-ethyl acetate) showed that all of the acceptor had been consumed. The mixture was diluted with CH2Cl2 (200 mL), and washed with 10% aqueous Na2S2O3, saturated aqueous NaHCO3 and brine. The dried (Na2SO4) material was concentrated and flash chromatography (7:1& ndash;4:1, hexane-ethyl acetate) afforded 1.78 g (92%) of 9 (n = 2). Rf = 0.5 (7:3 hexane-ethyl acetate).

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For 15a n = 6: 1H NMR (300 MHz, CDCl3): δ = 7.45-6.77 (m, 125 H), 5.56-5.52 (broad 6 H), 5.19 (s, 1 H), 4.98 (s, 1 H), 4.91-4.22 (m, 51 H), 4.12-3.56 (m, 49 H). 13C NMR (300 MHz, CDCl3): δ = 139.4, 139.2, 139.1, 139.0, 138.9, 138.6, 138.4, 138.3, 138.1, 138.0, 137.9, 137.0, 128.7, 128.7, 128.5, 128.4, 128.3, 128.1, 128.0, 127.9, 127.9, 127.8, 127.8, 127.7, 127.6, 127.5, 127.1, 127.1, [8 anomeric carbons comes at (100.9, 100.8, 100.5, 100.3, 100.1, 99.9, 98.7, 95.7 (α anomeric carbon)]. 83.3, 82.0, 81.9, 81.8, 81.7, 79.8, 78.1, 75.7, 75.5, 75.3, 75.1, 74.9, 74.7, 74.4, 74.1, 74.0, 73.6, 73.5, 73.2, 73.1, 73.0, 72.8, 72.7, 71.3, 70.3, 70.2, 70.1, 70.0, 69.9, 69.7, 69.6, 69.5, 69.4, 68.5, 67.6. FAB-MS (m/z) 3696 (M + Cs).