Preparation of Monosaccharide Having (Mercaptomethyl)diacetylene Compounds Using Solid-support as a Thiol Source

Abstract

This paper describes the efficient synthesis of mono­saccharides having (mercaptomethyl)diacetylene using Novabiochem^TM thiol 2-chlorotrityl resin. Coupling of an acetylene-terminated monosaccharide with the propargyl group that is attached to the solid-support afforded diacetylene-linked monosaccharide. The desired thiol compounds were obtained by cleavage of the chlorotrityl group in good yields. Preparation of the gold nanoparticles having the monosaccharides via gold-thiol reaction is briefly discussed.

acetylenic coupling - solid-support - thiol 2-chlorotrityl resin - saccharide - gold nanoparticle

References

1 Izumi M. Takagi T. Shibakami M. ITE Lett. Batteries  2002,  3:  707 

2a Glaser C. Ber. Dtsch. Chem. Ges.  1869,  2:  422 

2b Glaser C. Ann. Chem. Pharm.  1870,  154:  137 

2c Montierth JM. Demario DR. Kurth MJ. Schore NE. Tetrahedron  1998,  54:  11741 ; this reference describes the polymer-supported Cadiot-Chodkiewicz coupling of acetylenes to provide unsymmetrical diynes

2d Siemsen P. Livingston R. Diederich F. Angew. Chem. Int. Ed.  2000,  39:  2632 ; and references therein

3

Commercially available from Novabiochem, an affiliate of Merck KGaA, Darmstadt, Germany.

4

Introduction of Propargyl Bromide on Solid-support: Resin 1 (SH: 0.48 mmol/g) (3.00 g, 1.44 mmol) was placed in a polypropylene tube (Aldrich) fitted with a frit, and washed with DMF. Propargyl bromide 2 (0.37 mL, 4.32 mmol), DMF (10 mL), and NaH (0.17 g, 4.32 mmol) were then added to the tube, successively. After the reaction mixture was shaken for 3 d and filtered, the resin was washed with DMF, DMF-H₂O, and MeOH to give 3.11 g of propargylated resin 3.

5a Izumi M. Fukase K. Kusumoto S. Biosci. Biotechnol. Biochem.  2002,  66:  211 

5b Izumi M. Fukase K. Kusumoto S. Synlett  2002,  1409 

6

A Typical Procedure of the Glaser Coupling on Solid-support: The propargylated resin 3 (300 mg, 0.14 mmol) was placed in a centrifuging tube, and CuI (156 mg, 0.86 mmol), DMF (3.0 mL), pyridine (3.0 mL), and 5 (300 mg, 0.86 mmol) were successively added to the tube. The reaction mixture was then vigorously stirred at r.t. After 24 h, the resin was washed with DMF, DMF-H₂O, and MeOH to give the resin having monosaccharide 6.

7

A Typical Procedure of Deprotection of 4,6-Benzylidene and Cleavage of the Chlorotrityl Group of 6: Compound 6 (300 mg) was placed in a polypropylene tube fitted with a frit, and washed with CH₂Cl₂. Then CH₂Cl₂ (10 mL), H₂O (1.0 mL) and trifluoroacetic acid (TFA, 1.0 mL) were added to the tube, successively. After the reaction mixture was shaken for 12 h, the residual solution was removed by filtration and the resin was washed with MeOH and CH₂Cl₂. The resulting debenzlidenated resin having monosaccharide was shaken with a mixture of TFA (5.0 mL) and CH₂Cl₂ (5.0 mL) at r.t. for 12 h. After the resin was washed with MeOH (three times), the organic layer was combined, and concentrated in vacuo. The residue was purified with preparative silica-gel TLC (CHCl₃: MeOH = 10:1) to give 37.6 mg (82%) of the desired compound 7 (Table [1] , entry 10). Compound 7: ESI-Mass: m/z = 342.19 [M + Na]⁺.

8

A Procedure for Iodoalkynylation of Solid-support 3: The propargylated resin 3 (3.00 g, 1.44 mmol) was placed in a polypropylene tube fitted with a frit, and washed with DMF. Morpholine (2 mL), DMF (10 mL) and iodine (132 mg, 1.69 mmol) were added to the tube, successively. The reaction mixture was then shaken for 3 h. After the mixture was filtered, the resulting resin was washed with DMF and MeOH to give 3.31 g of 4.

9

A Typical Procedure of the Cadiot-Chodkiewicz-type Coupling Reaction: The iodoalkynylated resin 4 (300 mg) was placed in a polypropylene tube fitted with a frit, and washed with DMF. CuI (5.5 mg, 0.03 mmol), Pd(PPh₃)₄ (16.6 mg, 0.01 mmol), DMF (2.5 mL), pyridine (2.5 mL) and 5 (132 mg, 0.43 mmol) were successively added to the tube. The reaction mixture was then vigorously stirred at r.t. After 24 h, the solution was removed by filtration and the resin washed with DMF and MeOH.

10

See ref⁷. Compound 9: 29.0 mg (70%), ESI-Mass: m/z = 311.08 [M + Na]⁺. Compound 11: 41.1 mg (78%), ESI-Mass: m/z = 366.11 [M + Na]⁺. Compound 13: 27.8 mg (64%), ESI-Mass: m/z = 325.09 [M + Na]⁺.

11

Preparation of Gold Nanoparticles 14: To a phosphate buffer solution (3.0 mL, 10.0 mM) containing HAuCl₄ (39.3 mg, 0.10 mmol) was added 7 (32.9 mg, 0.10 mmol) in EtOH (3.0 mL) at 0 °C. The reaction mixture was then vigorously stirred. After stirring for 1 h, the gold nanoparticles that precipitated were obtained by centrifugation and then washed with MeOH. Removal of the residual solvent under reduced pressure afforded 11.5 mg of 14.

12

We believe that the ATR measurement is the most powerful and useful technique for the confirmation of the preparation of the gold nanoparticles that contain monosaccharides. An absorption band at 3104 cm^-1 was attributed to asymmetric N-H band of the amide group. Bands observed at 2362 and 2161 cm^-1 were attributed to alkyne. The presence of amine group was confirmed by bands at 1600 and 1425 cm^-1 (amide I-amide II). 14: IR: 3743, 3104, 2539, 2362, 2161, 2024, 1972, 1600, 1452, 1070, 755 cm^-1.