對(duì)甲氧基芐基（PMB）是也最穩(wěn)定的氨基保護(hù)基之一。它對(duì)大多數(shù)反應(yīng)都是穩(wěn)定的，在Bn存在下，可用CAN或DDQ氧化選擇脫PMB；同樣，在Boc和叔丁酯存在下，可用CAN氧化選擇脫PMB；也可用H2/Pd(OH)2去掉Bn，而保留PMB。
對(duì)甲氧基芐基（PMB）的引入
PMB一般采用MeOC6H4CH2Br或MeOC6H4CH2Cl和堿（K2CO3、DIPEA、NaH和DBU等）在有機(jī)溶劑(如DMF、二氯甲烷和乙腈等)中反應(yīng)來引入，或MeC6H4CHO/NaBH3CN或NaBH(OAc)3還原胺化等。
一、烷基化引入對(duì)甲氧基芐基（PMB）
J. Cossy; I. Pevet et al., Eur.J. Org. Chem., 2001, 15, 2841
Anhydrous K2CO3(780 mg, 5.66 mmol, 2.0 equiv.), n-Bu4NI (100 mg,0.28 mmol, 0.1 equiv.), and p-methoxybenzyl bromide (630 mg, 3.11 mmol,1.1 equiv.) were added successively to a solution of compound 1(700 mg, 2.83 mmol) in CH3CN (6 mL).After 1 h at 40°C and overnight at room temperature,the reaction mixture was diluted with ether, filtered, and concentrated under reducedpressure. The crude material was purified by flash chromatography (cyclohexane-AcOEt,95:5 to 90:10) to give 0.68 g(65%) of compound 2 as colorless oil. [α]D20 = +12.5 (c = 2.02, CHCl3).
二、烷基化引入對(duì)甲氧基芐基（PMB）示例2
R. Caputo; C.Romualdo et al., Eur. J. Org. Chem., 2002, 17, 3050
A magnetically stirred suspensionof compound 1 (0.39 g;2.84 mmol) and diisopropylethylamine (DIPEA, 25 mL; 0.14 mmol) in toluene (10mL) was gently warmed until a clear solution was obtained. 4-Methoxybenzyl chloride(2.3 mL; 17 mmol) was then added in one portion, and the resulting solution washeated under reflux, and also the intermediate N-monosubstitutedderivative were completely consumed (ca. 5 h, TLC monitoring). The reactionmixture was then cooled in an ice bath, diluted with ethyl acetate (0.2 L), and extracted with 10% aq. NH4Cl. The organiclayer was washed with brine and dried (Na2SO4), and the solvents wereevaporated under reduced pressure to afford a crude reaction product,chromatography of which on silica gel (petroleum ether/Et2O, 8:2) gavethe pure, oily title compound 2 (0.37 g; 85%).
三、還原胺化引入對(duì)甲氧基芐基（PMB）示例
P. Wipf; C. R. Hopkins et al., J. Org. Chem., 2001, 66(9), 3133
To a solution of 5.031 g (11.17 mmol) of amine 1 in 13 mL of MeOH was added at 0 °C 712.7 mg (11.34 mmol) of NaBH3CN followed by1.50 mL (1.68 g, 12.3mmol) of p-anisaldehyde and 0.5 mL of AcOH. The reaction mixture waswarmed to room temperature, stirred overnight, and quenched with H2O and solid Na2CO3. The viscoussuspension was transferred to a separatory funnel and extracted with CH2Cl2. The combined organicextracts were dried (Na2SO4) and concentrated in vacuo to give a bright yellow oilthat was purified by chromatography on SiO2(hexanes/EtOAc; 9:1) to afford 5.324 g (9.336 mmol, 84%) of amine 2 as a lightyellow oil: [α]D = -37.3 (c = 0.74, CHCl3).
對(duì)甲氧基芐基（PMB）的脫去
對(duì)甲氧基芐基（PMB）的脫去較多，除了常規(guī)的催化氫解外，CAN、 DDQ或SmI2氧化去保護(hù)和在TFA中加熱脫去也經(jīng)常應(yīng)用。
一、 DDQ脫去對(duì)甲氧基芐基（PMB）示例
S. D. Bull; S. G. Davies et al., J.Chem. Soc. Perkin Trans. 1, 2000, 22(1), 3765-3774
DDQ (1.15 g, 2.1 mmol) was added portionwise to a stirredsolution of compound 1 (400mg, 1.0 mmol) in MeCN-H2O (5 : 1, 6 mL) and stirred at RT. The reaction wasquenched by the addition of saturated aqueous sodium bicarbonate solution andstirred vigorously for ten minutes before extracting with Et2O. The combinedorganic extracts were dried (MgSO4), filtered andconcentrated in vacuo efore purification by column chromatography on silica gel (hexane-Et2O 2: 1) to givecompound 2 (246 mg, 79%)as a colourless oil.
二、CAN脫去對(duì)甲氧基芐基（PMB）示例
P. P. Obrien; W.David et al., Syn. Lett., 2000, 9, 1336
A mixture of compound 1 (104mg, 0.2 mmol) and CAN (350 mg, 0.6 mmol) in a 1:1 solution of MeCN-water (0.86 mL)was stirred at 0 °C for 30min. Brine (5 mL) was added and the mixture extracted with EtOAc (3 x10 mL).The combined organic extracts were dried (MgSO4) and evaporated under reducedpressure. Purification by chromatography on silica with petrol-EtOAc (6:1) aseluent gave amine 2 (65 mg, 87%) as a yellow oil.
三、TFA脫去酰胺對(duì)甲氧基芐基（PMB）示例
S. F. Martin; G.O. Dorsey et al., J. Med. Chem., 1998, 41(10), 1581
Compound 1 (200 mg, 0.810 mmol)was dissolved in trifluoroacetic acid (TFA) (10 mL), and the solution wasstirred for 24 h at room temperature. The reaction mixture was concentratedunder reduced pressure, and the residue was dissolved in CH2Cl2(50 mL). The organic layer
was washed with water (2 x25 mL), dried (MgSO4), and concentrated under reduced pressure to leave awhite solid that was purified by flash chromatography eluting with hexanes/EtOAc(1:1) containing 2% AcOH to give compound 2(180 mg, 77%) of as a white solid: mp 150-152 °C.
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