氨基的保护及脱保护策?- 百度文库 ر

H2/Pd-CPh3C-HHCl/CHCl3R1NHR2OHCl/MeOHHCl/H2OPh3C-ClPh3C-OHPh3C-OMeHOAcPh3C-OAc

1. 1. L. Zervas, D. M. Theodoropoulos., J. Am. Chem. Soc., 1956, 78, 1359; F. C. McKay, N. F.

Abertson., J. Am. Chem. Soc., 1957, 79, 4686; R. Schwyzer, W. Rittel., Helv. Chim. Acta., 1961, 44, 159

2. L. Hyun-Suk, P. Jeong-Ju et al., Bioorg. Med. Chem. Lett., 2004, 10, 2499; K. Yuji, T.

Ryuichi et al., Bioorg. Med. Chem., 2002, 10, 3829

3. S. Rita, K. Yeong-Sang et al., Tetrahedron Lett., 2003, 8, 1537

4. B. Bezas, L. Zervas., J. Am. Chem. Soc., 1961, 83, 719; G. Amiard, B. G. Offinet., Bull. Soc. Chim.

France., 1956, 698

5. Chandrasekhar, S., Babu, B. Nagendra et al., Tetrahedron Lett., 2003, 10, 2057; E. Janos,

K. Gyoergy et al., Tetrahedront., 2002, 44, 8921

TFAȥ׻ʾ

HFmocHNHTrtHNO1SOOHOTFACHCl3FmocHNHH2NO2SOOO

M. Firouz Mohd Mustapa, Richard Harris, Nives Bulic-Subanovic et al., J. Org. Chem., 2003, 21, 8185; S. Vinay, M. Mizio et al., Tetrahedron, 2002, 44, 9101

Compound 1 (3.5 g, 4.6 mmol) was treated with a 5% solution of trifluoroacetic acid (1.4 mL, 18 mmol, 4 equiv) in CHCl3 (27 mL) under inert conditions for 4 h. The resulting solution was diluted with CHCl3 (200 mL) and washed with sodium hydrogen carbonate (5% aq w/v, 2

Page 60 of 77

75 mL) and water (2 50 mL). The solvent was removed in vacuo. The material was then redissolved in CHCl3 (20 mL) and MeOH (20 mL), and the solvents were again removed in vacuo to yield compound 2 (2.1 g, 87%) as a pale yellow liquid.

4.1.2.2 TFA-TISȥ׻ʾ

OTrtHNOO1ONHFmocTFATIS, CH2Cl2H2NOO2OOHNHFmoc

Swall, Vinay; Matteuccl et al., Tetrahedron, 2002, 58(44), 9101-9110

Compound 1 (2.0 g, 2.71 mmol) was stirred with TFA (4.9mL), CH2Cl2 (4.9mL) and TIS (0.2 mL) for 1 h. Solvent was removed in vacuo and the residue purified by column chromatography (SiO2, MeOH/CHCl3, 1:9 v:v) to afford compound 2 (1.16 g, 91%) as a white solid.

4.1.2.3 TFA-Et3SiHȥ׻ʾ

TBSOTrtHN1NBocOTFAOBnEt3SiH, CH2Cl2H2N2NHOBnTBSOO

Pickersgill, I. Fraser; Rapoport, Henry; J. Org. Chem., 2000, 65(13), 4048-4057

To a stirred solution of compound 1 (3.34 g, 3.82 mmol) and triethylsilane (0.64 mL, 4.01 mmol) in CH2Cl2 (16 mL) cooled to 0 C was added dropwise TFA (16 mL). The resultant colorless solution was allowed to warm to rt, with stirring continued for 1 h. The solvents were evaporated, the residue was triturated with hexanes (5 x 50 mL), the hexane extracts were discarded, and the oily residue was partitioned between CHCl3/IPA (250 mL, 3/1) and 1 M NaOH (precooled to 0 C, 100 mL). The aqueous phase was extracted with further portions of CHCl3/IPA (2 x 200 mL, 3/1), and the combined organic phase was dried, filtered, and evaporated to give compound 2 (2.04 g, 100% crude yield) as a pale yellow oil.

Page 61 of 77

4.1.2.4 HOAcȥ׻ʾ

NHTrtNH1HOAcH2ONH2NH2

Vago, Istvan; Kalaus, Groergy et al., Heterocycles, 2001, 55(5), 873-880

0.85 g (2 mmol) of compound 1 was dissolved in the mixture of 20 mL of acetic acid and 0.5 mL of water. The solution was heated under argon at 60 oC for 1 h, and then allowed to cool to rt. The resulted dark solution was diluted with 200 mL of water; the triphenylmethanol was removed by extraction with ether. The pH of the watery phase was adjusted to a value of 8 with sodium carbonate solution, extracted with dichloromethane; the extract was dried with magnesium sulfate, evaporated to dryness in vacuumto give, compound 2 (0.24 g ,64 %) as unstable brown oil.

4.1.2.5 TBSBocŴBF3-HOAcȥ׻ʾ

OTBSTrtHN1NHBocBF3.Et2OAcOHH2N2OTBSNHBoc

Pickersgill, I, Fraser; Rapoport, Henry; J. Org. Chem., 2000, 65(14), 4048-4057 To a solution of 32 (2.67 g, 3.98 mmol) in CH2Cl2 (27 mL) cooled to 0 C were added glacial acetic acid (6.7 mL) and BF3.Et2O (0.529 mL, 4.17 mmol) dropwise, and the mixture was stirred at 0 C for 2 h. Cold (0 C) 1 M NaOH (160 mL) was added and the mixture partioned between CHCl3/IPA (320 mL, 3/1) and cold (0 C) 1 M NaOH (66 mL), followed by extraction with further portions of CHCl3/IPA (2 x 160 mL, 3/1). The combined organic phase was dried, filtered, and evaporated to a residue which was chromatographed (CH2Cl2/MeOH, 19/1 to 9/1) to give 33 (1.50 g, 88%) as a colorless oil: []22D = +3.1 (c = 1.0, CHCl3).

Page 62 of 77

4.2 2,4-лDMB

2,4-лDMBǽȶİ֮һ, Դ߻CbzPMBBnȶH2/8%Pd-C/EtOHɳȥBnN-DMB[1]ͬPd(PPh3)4/HOAc/THFɱN-DMB, ȥAlloc[2]лⷽѳDMBPMBѳƺϳ·ʱ2,4-аΪĵȼʹá

1Simig, Gyula; Doleschall, Gabor et al., Tetrahedron, 1985, 41(2), 479-484

2Boeckman, Robert K; Weidner, Charles H et al., J. Am. Chem. Soc., 1989, 111(20), 8036-8037

4.2.1 2,4-лDMB

2,4-лDMBһArCHO/NaBH3CNNaBH(OAc)3[1]ԭ롣

1. Moore, M. Caragh; Cox, Russell J et al., Tetrahedron, 1998, 54(31), 9195-9206

4.2.1.1 2,4-лDMBʾ

MeOOMeCOOMeNHOMeCOOMeNH2OHCNaBH3CN/MeOH1OMe

Moore, M. Caragh; Cox, Russell J et al., Tetrahedron, 1998, 54(31), 9195-9206 Methanolic HCl was added to a stirred solution of L-phenylalanine methyl ester (4.33 g24.16 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 20C for 30 min and then NaBH3CN (2.20 g35.01mmol) was added and the reaction stirred for a further 16h. The solvent was removed in vucuo, water (50 mL) added and the solution extracted with diethyl ether (3x 100 mL). The organic extracts were 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 of 2,4-dimethoxybenzylalcohol were removed by distillation under reduced presure

Page 63 of 77