醚氨基及氨基酸的各种保护基及去保护方法大全

醚、氨基及氨基酸的各种保护基及去保护方法大全

（整理有详细操作）

[Acetate] [Benzoatel] [Pivaloate] [Levulinate] [Back to Carb.

Synthesis]

Ac - (acetate) ester

Standard Protection Procedure

To a solution of the glycoside in dry pyridine (25 eq) under an inert atmosphere at room temperature, acetic anhydride (10 eq) is added and stirred until complete by TLC (usually 16 h). The reaction mixture is then poured into ice/water and extracted three times with chloroform. The combined organic layers are extracted with 3% HCl, saturated aqueous sodium bicarbonate, and water. The organic layer is then dried and concentrated in vacuo. The resulting residue is purified by flash chromatography (SiO2) if necessary.

Removal

The glycoside is dissolved in methanol and a solution of sodium methoxide in methanol (0.1 eq per -OAc) is added drop wise at 0°. The solution is warmed to room temperature and stirred under an inert atmosphere until complete by TLC (usually within a few hours). Amberlite cationic exchange resin is then added with vigorous stirring until the pH of the mixture is neutral. The mixture is then filtered and concentrated. The resulting residue is purified by flash chromatography (SiO2) if necessary.

OR

The Glycoside is dissolved in methanol and hydrazine hydrate (15 eq per -OAc) is added in two portions over 1.5 hours. The solution is stirred at room temperature under an inert atmosphere until complete by TLC (usually 6 hours). The solution is then neutralized with glacial acetic acid. The mixture is filtered through celite and concentrated. The resulting residue is purified by flash chromatography (SiO2) if necessary. References

J. Org. Chem., 1996, 61, 6442-6445.

"Synthetic Methods for Carbohydrates" Lemieux, Ch 6, pg. 90-115.

J. Chem. Soc., Perkin Trans. 1, 1996, 985-993.

Bz - (benzoate) ester

Standard Protection Procedure

To a solution of the glycoside dissolved in dry pyridine (0.3M), benzoyl chloride (4 eq per -OH) is added at room temperature under an inert atmosphere and stirred until complete by TLC (usually 16 h). Methanol is added and the solution was concentrated in vacuo. The residue was dissolved in DCM and washed with water, saturated copper sulfate, and brine. The organic layer is dried and concentrated in vacuo. The resulting residue is purified by flash chromatography (SiO2) if necessary. Removal

The glycoside is dissolved in MeOH and a solution of NaOH (2.5 eq per -OH) in MeOH is added slowly. The mixture is stirred at room temperature under an inert atmosphere till complete by TLC (usually 1 h) and then concentrated in vacuo. The residue is dissolved in ethyl acetate and the organic solution is washed twice with water, dried (sodium sulfate), and concentrated in vacuo. The resulting residue is purified by flash chromatography (SiO2) if necessary.

References

Tetrahedron, 1970, 26, 803-812.

Carb. Res., 1993, 244, 237-246.

Piv - (pivaloate) ester

Standard Procedure

The glycoside is dissolved in pyridine:DCM 2:1 and cooled to -20°. PivCl (1.2 eq per -OH) is then added drop wise under an inert atmosphere and the result is stirred at 0° until complete by TLC (usually 8 h). The mixture is then diluted with DCM and extracted with 5% HCl twice and once with water. The organic layer is then dried (sodium sulfate) and concentrated in vacuo. The resulting residue is purified by flash chromatography (SiO2) if necessary.

Removal

The glycoside is dissolved in MeOH, and a solution of sodium methoxide in methanol (10 eq per -OH) is added drop wise at room temperature under an inert atmosphere and stirred until the reaction is complete by TLC (usually 24 h). Aqueous HCl (10%) is added to the solution until neutral and the

resulting mixture is concentrated in vacuo. The residue is purified by flash chromatography (SiO2) if necessary.

References

Tet. Asym. 2000, 295-303.

J. Am. Chem. Soc. 1990, 112, 3693-3695.

Lev - (levulinate) ester

Standard Protection Procedure

To a solution of the glycoside in dry pyridine at room temperature under an inert atmosphere, levulinic anhydride (2 eq) is added drop wise. The reaction was stirred until complete by TLC (usually 24 h) and ice water is added. The mixture is extracted with chloroform and then the organic layer is back extracted with brine, dried (sodium sulfate), and concentrated in vacuo. The resulting residue is purified by flash chromatography (SiO2) if necessary.

Removal

The glycoside is dissolved in pyridine and hydrazine hydrate (1M in pyridine:acetic acid 3:2) is added at room temperature under an inert atmosphere. After addition of hydrazine is sufficient to consume starting material completely by TLC (usually a few minutes),

pentane-2,4-dione is added with cooling to quench the reaction. The mixture is diluted with chloroform and extracted once with water and once with brine. The organic layer is dried (sodium sulfate) and concentrated in vacuo. The residue is purified by flash chromatography (SiO2) if necessary.

References

JACS, 1975, 97, 1614-1615.

Tet. Lett., 1976, 52, 4875-4878.

[Benzyl] [Trityl] [PMP] [Allyl] [pMB] [Back to Carb. Synthesis] Bn - (benzyl) ether

Standard Protection Procedure

To a solution of sodium hydride (1.3 eq per -OH) in DMF, the glycoside (dissolved in DMF) is added drop wise at 0° under an inert atmosphere. The mixture is stirred for 30 minutes at 0° and benzyl bromide (1.3 eq per -OH) is added drop wise. *Note - a catalytic amount of TBAI or crown ether can be added. The reaction is stirred at room temperature until complete by TLC (usually 16 h) and methanol is added slowly to quench the reaction. The solution is then diluted with chloroform and water, extracted 3 times with water and once with brine. The organic layer is dried (sodium sulfate) and concentrated in vacuo. The resulting residue is purified by flash chromatography (SiO2) if necessary.

OR

To a solution of the glycoside in DCM, benzyl trichloroacetimidate (2 eq per -OH) is added drop wise (as a solution in cyclohexane - see third reference) with TfOH (catalytic - >1mol%). The result is stirred at room temperature under inert atmosphere until complete by TLC (usually overnight). Saturated aqueous sodium bicarbonate is added and the mixture is diluted with DCM. The organic layer is extracted once with water, once with brine, dried (sodium sulfate), and concentrated in vacuo. The resulting residue is purified by flash chromatography (SiO2) if necessary.

Removal

The glycoside is dissolved in 1:1 MeOH:tBuOH and palladium hydroxide (0.1 eq) is added at room temperature. A hydrogen atmosphere is added (balloon pressure) and the reaction is stirred until complete by TLC (usually 16 h). The mixture is then filtered and concentrated. *Note - catalytic glacial acidic acid may be added if the reaction isn't complete. The resulting residue is purified by flash chromatography (SiO2) if necessary.

References

J. Org. Chem., 1979, 44, 3442.

J. Am. Chem. Soc., 1971, 93, 1746.

Tr - (triphenyl methyl) or trityl ether

Standard Protection Procedure

To a solution of the glycoside, trityl chloride (1.1 eq for primary over secondary, 1.5 eq for each -OH otherwise), and triethylamine (1.5 eq for primary over secondary, 2 eq for each -OH otherwise) stirring in DMF under an inert atmosphere at room temperature, DMAP (0.05 eq) is added. The reaction is stirred until complete by TLC (usually overnight)

and then poured into ice-water. The mixture is extracted with chloroform and the organic layer is washed with saturated aqueous ammonium chloride and water, dried (sodium sulfate), and concentrated in vacuo. The resulting residue is purified by flash chromatography (SiO2) if necessary.

Removal

The glycoside is dissolved in ethanol and 5% palladium on charcoal is added under a hydrogen atmosphere. The reaction is stirred until complete by TLC (usually overnight) and filtered. The solution is concentrated and the residue is purified by flash chromatography (SiO2) if necessary. References

Tet. Lett., 1979, 2, 95-98.

JOC, 1978, 18, 2877-2881.

pMB - (para-methoxy benzyl) ether

Standard Protection Procedure

To a solution of sodium hydride (1.3 eq per -OH) in DMF, the glycoside (dissolved in DMF) is added drop wise at 0° under an inert

atmosphere. The mixture is stirred for 30 minutes at 0° and

para-methoxybenzyl bromide (1.3 eq per -OH) is added drop wise. *Note - a catalytic amount of TBAI or crown ether can be added. The reaction is stirred at room temperature until complete by TLC (usually 16 h) and methanol is added slowly to quench the reaction. The solution is then diluted with chloroform and water, extracted 3 times with water and once with brine. The organic layer is dried (sodium sulfate) and concentrated in vacuo. The resulting residue is purified by flash chromatography (SiO2) if necessary.

Removal

The glycoside is dissolved in DCM/H2O 20:1 and DDQ (up to 10 eq) is added at room temperature under an inert atmosphere. The reaction is stirred until complete by TLC (usually 24 h, may require heat) and diluted with DCM. The solution is extracted with saturated aqueous sodium bicarbonate, dried (sodium sulfate), and concentrated in vacuo. Product can then be purified by column chromatography if necessary. The resulting residue is purified by flash chromatography (SiO2) if necessary. References

JACS, 1992, 114, 2524-2536.

JACS, 1996, 118, 9265-9270.

Allyl - (allyl) ether

Standard Protection Procedure

To a solution of sodium hydride (1.3 eq per -OH) in DMF, the glycoside (dissolved in DMF) is added drop wise at 0° under an inert atmosphere. The mixture is stirred for 30 minutes at 0° and ally bromide (1.3 eq per -OH) is added drop wise. *Note - a catalytic amount of TBAI or crown ether can be added. The reaction is stirred at room temperature until complete by TLC (usually 16 h) and methanol is added slowly to quench the reaction. The solution is then diluted with chloroform and water, extracted 3 times with water and once with brine. The organic layer is dried (sodium sulfate) and concentrated in vacuo. The resulting residue is purified by flash chromatography (SiO2) if necessary.

OR

To a solution of the glycoside in DCM, benzyl trichloroacetimidate (2 eq per -OH) is added drop wise (as a solution in cyclohexane - see third reference) with TfOH (catalytic - >1mol%). The result is stirred at room temperature under inert atmosphere until complete by TLC (usually overnight). Saturated aqueous sodium bicarbonate is added and the mixture is diluted with DCM. The organic layer is extracted once with

water, once with brine, dried (sodium sulfate), and concentrated in vacuo. The resulting residue is purified by flash chromatography (SiO2) if necessary.

Removal

The glycoside is dissolved in AcOH:water 20:1 and Palladium chloride (1.5 eq) followed by sodium acetate (5 eq) is added. The mixture is stirred under an inert atmosphere at room temperature until complete by TLC (usually overnight). Ethyl acetate is added and the mixture is extracted 2 times with saturated aqueous sodium bicarbonate. The organic layer is then extracted once with brine, dried (sodium sulfate), and concentrated in vacuo. The resulting residue is purified by flash chromatography (SiO2) if necessary.

References

Tet. Lett., 1997, 40, 13,509-13,556.

JOC, 1973, 18, 3224.

J. Chem. Soc. Perkin Trans. I, 1985, 2247-2250.

JACS, 1991, 113, 2092-2112.

PMP - (p-methoxyphenyl) ether

Standard Protection Procedure

To a solution of the glycoside in THF under an inert atmosphere is added triphenylphosphine (1.3 eq), diethylazocarboxylate (1.3 eq), and

p-methoxyphenol (3 eq). The resulting solution is heated to 80° and stirred until complete by TLC (usually 2 h). The mixture is concentrated in vacuo and purified by flash chromatography (SiO2).

Removal

The glycoside is dissolved in acetonitrile:water 4:1 at room temperature under an inert atmosphere and CAN (5 eq) is added. The mixture is stirred until complete by TLC (usually less than 1 h) and diluted with chloroform. The resulting solution is washed with water and saturated sodium chloride solution. The organic layer is dried (sodium sulfate) and concentrated in vacuo. The residue can then be purified by flash chromatography (SiO2) if necessary.

References

Tet. Lett., 1988, 29, 1389-1390.

Heterocycles, 1990, 31, 1555-1563.

[TMS] [TES] [TIPS] [TBS] [TBDPS] [Back to Carb. Synthesis] TMS - (trimethyl silyl) ether

Standard Protection Procedure

To a solution of the glycoside and triethylamine (2 eq) stirring in THF at 0° under an inert atmosphere, is added drop wise TMS-Cl (1.5 eq). The result was allowed to warm to room temperature and stirred until complete by TLC (usually 6 h). The solution is then concentrated in vacuo and the residue taken on directly to next step.

Removal

The glycoside is dissolved in THF (~2M) and TBAF (1M solution in THF) is added drop wise at 0° under inert atmosphere. The reaction is allowed to warm to room temperature and stirred until complete by TLC (usually a few hours - if not complete in this time more TBAF solution may be added). *Note - equal volumes of glacial acetic acid (compared to TBAF solution.) may be added to prevent removal of acetates or other sensitive protecting groups. The reaction mixture is concentrated in vacuo and the residue is purified by flash chromatography (SiO2) if necessary.

References

JACS, 1972, 94, 2549-2550.

TES - (triethyl silyl) ether

Standard Protection Procedure

To a solution of the glycoside and imidazole (2 eq) stirring in DMF at 0° under an inert atmosphere, is added drop wise TES-Cl (2 eq). The result is allowed to warm to room temperature and stirred until complete by TLC (usually overnight). An equal volume of ether is added and the reaction mixture is extracted three times with water and once with brine. The organic layer is dried (sodium sulfate) and concentrated in vacuo. The product can then be purified by flash chromatography (SiO2) if necessary. Removal

The glycoside is dissolved in THF (~2M) and TBAF (1M solution in THF) was added drop wise at 0° under an inert atmosphere. The result is allowed to warm to room temperature and stirred until complete by TLC (usually a few hours - if not complete in this time more TBAF solution may be added). *Note - equal volume of glacial acetic acid (compared to TBAF

solution.) may be added to prevent removal of acetates or other sensitive protecting groups. The reaction mixture is concentrated in vacuo and the residue is purified by flash chromatography (SiO2) if necessary. References

Helv. Chim. Acta, 1981, 64, 2002-2021.

TIPS - (triisopropyl silyl) ether

Standard Protection Procedure

To a solution of the glycoside stirring in DMF at 0° under an inert atmosphere, TIPS-Cl (1.3 eq) and imidazole (1.5 eq) were added succinctly. The result was allowed to warm to room temperature and stirred until complete by TLC (usually overnight). The mixture is diluted with equal volume of chloroform and extracted three times with water and once with brine. The organic layer is dried (sodium sulfate) and concentrated in vacuo. The resulting residue is purified by flash chromatography (SiO2) if necessary.

Removal

The glycoside is dissolved in THF (~2M) and TBAF (1M solution in THF) was added drop wise at 0° under an inert atmosphere. The result is allowed to warm to room temperature and stirred until complete by TLC (usually a few hours - if not complete in this time more TBAF solution may be added). *Note - equal volume of glacial acetic acid (compared to TBAF solution.) may be added to prevent removal of acetates or other sensitive protecting groups. The reaction mixture is concentrated in vacuo and the residue is purified by flash chromatography (SiO2) if necessary. References

JOC, 1980, 45, 4797-4798.

TBS - (tert-butyl dimethyl silyl) ether

Standard Procedure

To a solution of the glycoside in DMF at 0° under an inert atmosphere, TBS-Cl (1.1 eq for selective primary -OH protection, 1.3 eq otherwise) and imidazole (1.3 to 1.5 eq) were added succinctly. The result was allowed to warm to room temperature and stirred until complete by TLC (usually overnight). The mixture is diluted with equal volume of chloroform and

extracted three times with water and once with brine. The organic layer is dried (sodium sulfate) and concentrated in vacuo. The resulting residue is purified by flash chromatography (SiO2) if necessary.

OR

To a solution of the glycoside and distilled 2,6-lutidine (2.1 eq) in dry DCM under an inert atmosphere at -78°, TBS-OTf is added drop wise over 30 minutes. The result is stirred until complete by TLC (usually 30 minutes - if not complete more TBS-OTf may be added) and methanol is added. The mixture is diluted with chloroform, washed with water and brine, dried over magnesium sulfate and concentrated in vacuo. The resulting residue is purified by flash chromatography (SiO2) if necessary.

Removal

The glycoside is dissolved in THF (~2M) and TBAF (1M solution in THF) was added drop wise at 0° under an inert atmosphere. The result is allowed to warm to room temperature and stirred until complete by TLC (usually a few hours - if not complete in this time more TBAF solution may be added). *Note - equal volume of glacial acetic acid (compared to TBAF solution.) may be added to prevent removal of acetates or other sensitive protecting groups. The reaction mixture is concentrated in vacuo and the residue is purified by flash chromatography (SiO2) if necessary. References

JACS, 1997, 119, 449-450.

JACS, 1972, 94, 6190-6191.

JOC, 1987, 52, 622-635.

TBDPS - (tert-butyl diphenyl silyl) ether

Standard Procedure

The glycoside is dissolved in DMF at room temperature under an inert atmosphere and treated with imidazole (2 eq per -OH) followed by TBDPS-Cl (1.5 eq per -OH). The reaction mixture is stirred until complete by TLC (usually overnight), diluted with ether and washed with 1M HCl followed by brine. The organic layer is dried (magnesium sulfate) and concentrated in vacuo. The resulting residue is purified by flash chromatography (SiO2) if necessary.

Removal

To a solution of the glycoside in THF at room temperature in a Nalgene container, commercially available 30% HF in pyridine is added drop wise under an inert atmosphere. The result is stirred until complete by TLC (usually 16 h) and diluted with slow addition of saturated sodium bicarbonate. Chloroform is added and the mixture is extracted

successively with water, saturated copper sulfate, and brine. The organic layer is then dried (sodium sulfate) and concentrated. The resulting residue is purified by flash chromatography (SiO2) if necessary. References

JACS, 1997, 119, 449-450.