有机合成中的保护基

HO
TBSO
HF (2 eq) MeCN, 50 oC
OTBS
92%
OTBS
TBAF (1 eq) THF, 0 oC
TBSO
OH
83%
Collington, E. W.; Finch, H. Smith, I. J. Tetrahedron Lett., 1985, 26, 681.
O
cleavage
TBDPS ether： TBDPSCl / imidazole / DMF, catalyst: DMAP, solvent: CH2Cl2
BnO OH OH
OH
BnO
TBDPSCl(1.2eq)
imidazole(1.2eq) DMF, rt,
OH OH
80%
OTBDPS
Nicolaou, K. C.; Pavia, M. R.; Seitz, S. P. J. Am. Chem. Soc., 1981, 103, 1224.
R = ClCH2CO
O
O Ph
O O
O
OH
AcO
S
H2NHN SH
HO
Dioxane, i-Pr2NEt
O
O
O AcO
OH
O
O Ph
O O
O
40%
Smith, A.B.; Hale, K. J.; Vaccaro, H. A.; Rivero, R. A. J. Am. Chem. Soc, 1991, 113, 2112.
(5) 保护基以后的化合物对分离、纯化、各种层析技术要稳定。 (6) 保护基团在高度专一的条件下能选择性、高效率地被除去。 (7) 去保护过程的副产物和产物能容易被分离。

呼之即来，挥之即去。


切莫请神容易，送神难。
羟基的保护基
1). 酯类保护基 t-BuCO (Pivalyl新戊酰基; Piv); PhCO; MeCO; ClCH2CO et al.
O OH CO2Me
O OTMS CO2Me
COOBu-t Me3SiCl-Im
O
H
COOBu-t
100 oC, 90 min. O
H
OTBS
O
O
OTBS
O
O
100%
Kerwin, S. M.; Paul, A. G.; Heathcock, C. H. J. Org. Chem., 1987, 52, 1686
O
AcHN
O OBn
NH2NH2 (15eq)
HOAc-HOMe rt, 12 h
OBn OBn HO
O
AcO
OBn OBn
O
AcHN
O OBn
74%
Cook, A. F.; Maichuk, D. T. J. Org. Chem., 1970, 35, 1940.
OR AcO
RO
O
O
O AcO
OR
Me2BBr/CH2Cl2

MTM AgNO3/2,6-lutidine; HgCl2/CaCO3

MEM ZnBr2/CH2Cl2;HBr/THF;TiCl4/CH2Cl2; Me2BBr/CH2Cl2

BOM Na/NH3/EtOH, H2/Pd(OH)2/C;Raney-Ni/EtOH;

BF3/PhSH/CH2Cl2
allyl (烯丙基醚)

reagent: Allyl bromide

cleavage: t-BuOK/DMSO/NaOH
烷氧基烷基醚：
MOM(甲氧基甲基醚) methoxymethyl ether
MTM(甲硫基甲基醚) methylthiomethyl ether MEM(甲氧基乙氧基甲基醚) methoxyethoxymethyl ether
OH
HO
PivCl (1eq)
Py-CH2Cl2 OH 0-25 oC
OH
HO
O
O
90%
Nicolaou, K. C.; Webber, S. E. Synthesis, 1986, 453
酯类保护基的除去(cleavage)
碱性条件下水解， 水解能力： t-BuCO(Piv) < PhCO < MeCO < ClCH2CO
Cleavage
OTBDPS OH OMe
OTBS
HOAc-THF-H2O 3:1:1
OH
OTBDPS OH OMe
87%
OH OH
Marshell, J. A.; Sedrani, R. J. Org. Chem., 1991, 56, 5496.
Cleavage
TBSO
O OH
OPiv OTBS O
Cleavage
TBDMSO O O
N3
O O
CO2Me OTBDMS
TBAF THF, rt
HO O O
N3
O O
CO2Me OTBDMS
90% Nakata, T.; Fukui, M.; Oishi, T. Tetrahedron Lett., 1988, 29, 2219.
Cleavage
PMB (对甲氧基苄基醚); DMB or DMPB (3,4-二甲氧基苄基醚)

reagent: PMBCl; p-MeOC6H4CH2O-C(=NH)CCl3

cleavage: DDQ, CAN
Tr (三苯甲基醚)

reagent: TrCl/Py/DMAP; TrOTf/2,6-lutidine
O
O O
O OTBS
N O
OH
O
OTIPS O
H
O
HF / MeCN
OTIPS
O
O
O O
O
N
H
OH
O
OH
O
OH O
H
O
OH
FK-506, 73%
Nakatsuka, M.; Ragan, J. A.; Sammakia, T.; Smith, D. B.; Uehling, D. E.; Schreiber, S. L. J. Am. Chem. Soc., 1990, 112, 5583.
Reagents: Acetone; benzaldehyde,cyclo-ketone
Cleavage: Acid; Lewis acid
醛酮的保护：
O,O-acetals: 1,3-dioxalane (5-number rining) Catalyst: p-TsOH, CSA, PPTs
TBDMS ether： TBDMSCl / imid. / DMF; TBDMSOTf / 2,6-lutidine
OH OBMPO O
TBDMSOTf
OBz
2,6-di-tert-buylpyridine CH2Cl2, rt, 24 h
OTBS OBz
OBMPO O
Hikota, M.; Tone, H., Horita, K.; Yonemitsu, O. J. Org. Chem., 1990, 55, 7.
95% Nicolaou, K. C.; Webber, S. E. Synthesis, 1986, 453
ClCH2CO的去除可以用硫脲，氨/甲醇，苯，吡啶水溶液， NH2CH2CH2SH, NH2CH2CH2NH2, PhNHCH2CH2NH2 等除去。
O
Cl
OBn OBn
O
O
AcO
OBn OBn
O
TBSO
HF-CH3CN -25 oC
O OH
OPiv OH O
O
85%
Danishefsky, S. J.; Armistead, D. M.; Wincott, F. E.; Selnick, H. G; Hungate, R. J. Am. Chem. Soc., 1989, 111, 2967.

claevage: HCO2H-H2O; HCO2H-t-BuOH; HCl/MeCN; Na/NH3
tert-butyl (叔丁基醚)

reagent: isobutene/CH2Cl2; t-BuO-C(=NH)CCl3

cleavage: HCO2H; CF3CO2H; HBr-HOAc, FeCl3; TiCl4; TMSI
硅醚保护基的除去： （F-Si 142 kcal/mol; O-Si 112 kcal/mol） 通常用 HF / CH3CN; TBAF / THF; HF.Py / CH3CN
TMS ether： TMSCl or TMSOTf in pyridine, NEt3, i-Pr2NEt, imidazole, DBU
BOM(苄氧基甲基醚) benzyloxymethyl ether
SEM(三甲硅基乙氧基甲基醚) trimethylsilylethoxymethyl ether
reagents: RCl or RBr/NaH/THF

cleavage: MOM HCl/THF/H2O(1:2:1); Lewis acid: Me3SiBr/CH2Cl2;

SEM HCl/MeOH; Lewis acid;
THP(四氢吡喃) tetrahydropyrane ether
reagents: DHP(3,4-dihydro-2H-pyran)
cleavage: HOAc/THF/H2O (4:2:1)
1,2或1,3-二醇的保护：