penta-tert-butyl γ-L-glutamyl-γ-L-glutamyl-γ-L-glutamyl-L-glutamate | 88443-03-2

分子结构分类

有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物

中文名称

——

中文别名

——

英文名称

penta-tert-butyl γ-L-glutamyl-γ-L-glutamyl-γ-L-glutamyl-L-glutamate

英文别名

L-γ-glutamyl-L-γ-glutamyl-L-γ-glutamyl-L-glutamic acid pentakis-t-butyl ester；H-gGlu(OtBu)-gGlu(OtBu)-gGlu(OtBu)-Glu(OtBu)-OtBu；ditert-butyl (2S)-2-[[(4S)-4-[[(4S)-4-[[(4S)-4-amino-5-[(2-methylpropan-2-yl)oxy]-5-oxopentanoyl]amino]-5-[(2-methylpropan-2-yl)oxy]-5-oxopentanoyl]amino]-5-[(2-methylpropan-2-yl)oxy]-5-oxopentanoyl]amino]pentanedioate

penta-tert-butyl γ-L-glutamyl-γ-L-glutamyl-γ-L-glutamyl-L-glutamate化学式

CAS

88443-03-2

化学式

C₄₀H₇₀N₄O₁₃

mdl

——

分子量

815.015

InChiKey

YPQROFHHLOUMPI-FWEHEUNISA-N

BEILSTEIN

——

EINECS

——

物化性质

熔点：

119-119.5 °C
沸点：

884.8±65.0 °C(Predicted)
密度：

1.117±0.06 g/cm3(Predicted)

计算性质

辛醇/水分配系数(LogP)：

3
重原子数：

57
可旋转键数：

29
环数：

0.0
sp3杂化的碳原子比例：

0.8
拓扑面积：

245
氢给体数：

4
氢受体数：

14

上下游信息

上游原料

中文名称	英文名称	CAS号	化学式	分子量
——	tetra-tert-butyl L-γ-glutamyl-L-γ-glutamyl-L-glutamate	73167-55-2	C₃₁H₅₅N₃O₁₀	629.792
——	tri-tert-butyl γ-L-glutamyl-L-glutamate	88063-78-9	C₂₂H₄₀N₂O₇	444.569
——	tetra-tert-butyl N--L-γ-glutamyl>-L-glutamate	32719-57-6	C₃₉H₆₁N₃O₁₂	763.926
——	tri-tert-butyl N--L-glutamate	32719-56-5	C₃₀H₄₆N₂O₉	578.703
——	Z-L-Glu-(O-t-Bu)-O-t-Bu	16881-41-7	C₂₁H₃₁NO₆	393.48
Z-谷安酸叔丁基酯	(S)-2-(benzyloxycarbonylamino)pentanedioic acid tert-butyl ester	5891-45-2	C₁₇H₂₃NO₆	337.373

下游产品

中文名称	英文名称	CAS号	化学式	分子量
——	hexa-tert-butyl γ-L-glutamyl-γ-L-glutamyl-γ-L-glutamyl-γ-L-glutamyl-L-glutamate	73167-56-3	C₄₉H₈₅N₅O₁₆	1000.24
——	L-γ-glutamyl-L-γ-glutamyl-L-γ-glutamyl-L-γ-glutamyl-L-γ-glutamyl-L-glutamic acid heptakis-t-butyl ester	118252-57-6	C₅₈H₁₀₀N₆O₁₉	1185.46
——	Boc-Asp-Glu(OtBu)-Glu(OtBu)-Glu(OtBu)-OtBu	——	C₄₉H₈₃N₅O₁₈	1030.22

反应信息

作为反应物：

描述：

penta-tert-butyl γ-L-glutamyl-γ-L-glutamyl-γ-L-glutamyl-L-glutamate 在 diethyl cyanophosphoridate 、三乙胺作用下，以 N,N-二甲基甲酰胺为溶剂，反应 3.0h，生成 (2S)-2-[[(4S)-4-carboxy-4-[[(4S)-4-carboxy-4-[[(4S)-4-carboxy-4-[[5-[methyl-[(2-methyl-4-oxo-1H-quinazolin-6-yl)methyl]amino]thiophene-2-carbonyl]amino]butanoyl]amino]butanoyl]amino]butanoyl]amino]pentanedioic acid;2,2,2-trifluoroacetic acid

参考文献：

名称：

Syntheses and thymidylate synthase inhibitory activity of the poly-.gamma.-glutamyl conjugates of N-[5-[N-(3,4-dihydro-2-methyl-4-oxoquinazolin-6-ylmethyl)-N-methylamino]-2-thenoyl]-L-glutamic acid (ICI D1694) and other quinazoline antifolates

摘要：

Thirteen poly-gamma-glutamates derived from several novel antifolates have been synthesized by a convergent route. The syntheses of poly-gamma-glutamyl conjugates of N-[5-[N-(3,4-dihydro-2-methyl-4-oxoquinazolin-6-ylmethyl)-N-methylamino]-2-thenoyl]-L-glutamic acid (8) (ICI D1694), 2-desamino-N10-propargyl-5,8-dideazafolic acid (6), 2-desamino-2-methyl-N10-propargyl-5,8-dideazafolic acid (7), 2-desamino-2-methyl-N10-propargyl-2'-fluoro-5,8-dideazafolic acid (9), and 2-desamino-2-methyl-4-chloro-N10-propargyl-2'-fluoro-3,5,8-trideazafolic acid (11) are described. A key step in the route involves coupling of an alpha-tert-butyl-protected poly-gamma-glutamate of the required chain length to the appropriate 5,8-dideazapteroic acid, obtained by carboxypeptidase G2 cleavage of the parent monoglutamate, if available, or by chemical synthesis. Deprotection with trifluoroacetic acid in the final step gave the desired poly-gamma-glutamyl antifolates as their trifluoroacetate salts. As inhibitors of thymidylate synthase, these polyglutamates were more potent in every case than the corresponding non-polyglutamylated drug.

DOI：

10.1021/jm00083a008
作为产物：

描述：

Z-谷安酸叔丁基酯在 palladium on activated charcoal