2,4-二甲氧基芐基（DMB）是較穩(wěn)定的胺基保護基之一,對催化氫解較Cbz、PMB和Bn穩(wěn)定，故用H2/8%Pd-C/EtOH處理，則可除去Bn，而保留N-DMB。同樣，用Pd(PPh3)4/HOAc/THF處理，則可保留N-DMB, 而除去Alloc。酰胺的芐基，常規(guī)加氫方法不易脫除，但DMB和PMB容易脫除。在設計合成路線時，2,4-二甲氧基芐胺常被用為氨的等價物加以使用。
2,4-二甲氧基芐基（DMB）引入
2,4-二甲氧基芐基（DMB）一般由ArCHO/NaBH3CN或NaBH(OAc)3還原胺化引入。
Moore, M. Caragh; Cox, Russell J et al., Tetrahedron, 1998, 54(31), 9195-9206
Methanolic HCl was added toa stirred solution of L-phenylalanine methyl ester (4.33 g，24.16 mmol) in methanol (100 mL) to adjust to pH 6.2,4-Dimethoxybenzaldehyde (4.82, 29.00 mmol)was then added, the solution stirred at 20°C for 30 min and then NaBH3CN (2.20 g，35.01mmol) was added and the reaction stirred for afurther 16h. The solvent wasremoved in vucuo, water (50 mL) added and the solution extracted with diethyl ether(3x 100 mL). The organic extractswere combined: washed with an aqueous solution of FeSO4, dried (MgSO4), filtered and reduced in vucuo,to afford a crude pruduct as a pale yellow oil. Impurities of2,4-dimethoxybenzylalcohol were removed by distillation under reduced presure(furnace temparature 110°C,0.1 mmHg). The product could be further purified by chromatography (hexane:ethylacetate, 50 : 50) to give compound 1 (3.71 g, 11.26 mmo1, 46.6%) [α]21D= - 65.22 (c = 0.01, EtOH).
2,4-二甲氧基芐基（DMB）脫去
DMB容易用酸脫去，如用TFA, TosOH或HCl的有機溶液在0℃或室溫即可順利除去。采用TFA/i-Pr3SiH/CH2Cl2時,N-Fmoc可以穩(wěn)定不動。其他如DDQ/CH2Cl2也能很方便的脫去DMB，而叔丁酯和N-Boc可以不受影響。
一、2,4-二甲氧基芐基（DMB）酸脫去示例
Hill, Bryan; Liu, Yong et al., Org.Lett.,2004, 6(23), 4285-4288
Route A: To a cooled 0°C solution of Sulfonamide 3 (43.5 mg, 0.117 mmole) and CH2Cl2 (2.6 mL)wasadded TFA (1.1 mL). The reaction mixture immediately turned pink. The reactionwas stirred at 0°Cfor 4.5 hrs then the solvent was removed in vacou to yield a pink solid. The solid was suspended in acetone and filteredthru a plug of cotton (acetone rinse). The filtrate was evaporated and theresidue purified by flash chromatography (15:85 EtOAc:Hexanes) yieldedsulfonamide 2 (23.4 mg, 90%) as a clear colorless oil.
Route B: A solution of sulfonamide 1 (96.2 mg, 0.286 mmole), 1N HCl (3.8 mL) and THF (3.8 mL)was stirred at rt overnight. The mixture was diluted with Et2O, washed with aq. NaHCO3, brine, dried over MgSO4, filtered and concentrated. Flashchromatography (15:85 EtOAc:Hexanes) yielded sulfonamide 2 (55.2 mg,87%).
二、DDQ脫去2,4-二甲氧基芐基（DMB）示例
Dagoneau,Christelle; Denis, Jean-Noeel et al., Syn.Lett., 1999, 5, 602-604
A solution of ester 1(0.08mmol) andDDQ (0.28mmol) in CH2Cl2/H2O (19/1, 6mL) was stirred for 1 day at r.t. The mixturewas then diluted with CH2Cl2and treated bya saturated aqueous solution of NaHCO3. Classical work-up, followed bycolumn chromatography (silica gel, AcOEt/pentane:1/9) afforded the N-Bocamine 2 as a colorless oil.
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