available from -mannose; [31] also O-deacetylation (Ǟ 9), tetrabutylammonium fluoride (TBAF) in acetic acid/THF gave 6-O-unprotected mannoside 22 which served as man-benzylation (Ǟ 10), subsequent acid-catalyzed ortho ester opening and then O-acetylation (Ǟ 11α,β) followed essen-nosyl residue c. Its structure was confirmed with the help of the 1 H-NMR data of derivative 22a. tially published procedures. [32,33] Selective 1-O-deacetylation with ammonium carbonate in DMF afforded 12α,β in high yield. Ensuing treatment with trichloroacetonitrile in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) afforded almost exclusively α-trichloroacetimidate 13 (α/β ഠ 17:1) in 93% yield; 13 provides mannosyl residues d and f in the construction of tetramannosyl building block 4. The 2-O-acetyl group in 13 promotes the desired α-selective O-glycosylations. Scheme 4b Scheme 4a. R ϭ Bn Experimental Section General: Solvents were purified in the usual way; boiling range of petroleum ether: 35Ϫ60°C. Ϫ Melting points are uncorrected. Ϫ Optical rotations: PerkinϪElmer polarimeter 241 MC; 1-dm cell, temperature 20°C. Ϫ Thin-layer chromatography (TLC): Plastic sheets, silica gel 60 F 254 (Merck; layer thickness 0.2 mm). Ϫ Column chromatography: Kieselgel 60 (Merck; 0.063Ϫ0.200 mm). Ϫ Flash chromatography: Silica gel (J. T. Baker, particle size 40 mm). Ϫ 1 H NMR: Bruker AC 250 (250 MHz) Cryospec, Bruker DRX 600 (600 MHz), internal standard tetramethylsilane (TMS). Ϫ 31 P NMR: Jeol JNM-GX 400; external standard 85% phosphoric acid. Ϫ FAB MS: Finnigan MAT 312/AMD 5000; matrix NBOH (ϭ 3nitrobenzyl alcohol). Ϫ Elemental analyses: Heraeus CHN-O-Rapid.
O-(2-Azido-6-O-benzoyl-2-deoxy-␣-D-glucopyranosyl)-(1Ǟ6)-2,3:4,5-di-O-cyclohexylidene-1-O-(1R)-menthyloxycarbonyl-D-myoinositol (7):
A solution of benzoyl cyanide (0.79 g, 5.78 mmol) in dry acetonitrile (10 mL) was added dropwise within 1 h to a solution of crude 6 [21] (4.1 g, 5.78 mmol) in dry acetonitrile/diethyl ether/triethylamine (10:7:3, 200 mL) at Ϫ60°C under nitrogen. The mixture was stirred for 2 h at Ϫ60°C. Within 2 h, the mixture was warmed up to room temp. and concentrated in vacuo. The residue was purified by flash chromatography with toluene/ethyl acetate (5:1) to yield 7 (3.2 g,, 68%) as a colorless foam which was lyophilized from dioxane.Ϫ TLC (petroleum ether/ethyl acetate, 6:4): R f ϭ 0.45; (toluene/ethyl acetate, 3:1): R f ϭ 0.26. Ϫ [α] D ϭ ϩ14 (c ϭ 1, chloroform). Ϫ 1 H NMR (250 MHz; CDCl 3 ): δ ϭ 0.72Ϫ0.75 (d, 3 J ϭ 6.9 Hz, 3 H, CH 3 ), 0.80Ϫ1.10 (2 d, m, 9 H, 2 CH 3 , H Mnt ), Scheme 5b. R ϭ Bn 1. 40Ϫ1.76 (m, 24 H, 20 H cycloh. , 4 H Mnt ), 1.86Ϫ2.12 (m, 2 H, 2 H Mnt ), 2.84 (d, 3 J 3b,OH ϭ 2.6 Hz, 1 H, OH), 3.20 (dd, 3 J 1b,2b ϭ 3.6, 3 J 2b,3b ϭ 10.3 Hz, 1 H, 2b-H), 3.38 (ddd, 3 J 4b,OH ϭ 4.0, 3 J 3b,4b ϭ zole as activating agent and then oxidation with tert-butyl 3 J 4b,5b ϭ 9.5 Hz, 1 H, 4b-H), 3.53 (dd, 3 J 4a,5a ϭ 10.8, 3 J 5a,6a ϭ 8.5
Hz, 1 H, 5a-H), 3.60(d, 3 J 4b,OH ϭ 3.9 Hz, 1 H, OH), 3.93Ϫ4.11 hydroperoxide gave Z-protected aminoethyl phosphate de-(m, 4 H, 4a-, 6a-, 3b-, 5b-H), 4.33Ϫ4.41 (m, 2 H, 6b-, 3a-H), rivative 38 in 81% yield (Scheme 5b). Now, the 1a-O-acetyl 4.45Ϫ4.58 (m, 2 H, H Mnt , 2a-H), 4.89Ϫ4.95 (m, 2 H, 6bЈ-, 1a-H), group was removed under Zemple ´n conditions (Ǟ 39), thus 5.29 (d, 3 J 1b,2b ϭ 3.6 Hz, 1 H, 1b-H), 7.41Ϫ7.61 (m, 3 H, m, ppermitting attachment of the ceramide 1-phosphate moiety. COPh), 8.02Ϫ8.06 (m, 2 H, OCOPh). Ϫ C 42 H 59 N 3 O 13 (813.94): To this end, reaction of 39 with phosphite amide derivative calcd. C 61.98, H 7.31, N 5.16; found C 61.49, H 7.44, N 5.72.
2 in the presence of tetrazole followed by oxidation with
O-(2-Azido-6-O-benzoyl-3-O-benzyl-2-deoxy-␣-D-glucopyrano-
tert-butyl hydroperoxide was carried out, leading to the corsyl)-(1Ǟ6)-2,3:4,5-di-O-cyclohexylidene-1-O-(1R)-menthylresponding phosphotriester, which gave with dimethylamine oxycarbonyl-D-myo-inositol (3): To a solution of 7 (10 g, 12.3 mmol) in ethanol diester 40 in 60% overall yield. Simultaneous in dry dichloromethane (35 mL) freshly prepared Ag 2 O (10 g),