新产品编号:438723

Chemical Name: N2-[3(R)-(Decanoyloxy)tetradecanoyl]-O3-[2-[3(R)-(decanoyloxy)tetradecanamido]-3-O-[3(R)-(decanoyloxy)tetradecanoyl]-2-deoxy-4-O-phosphono-beta-D-glucopyranosyl]-L-serinamide triethylammonium salt
CAS No. 216014-82-3
项目整合开发状态: Preclinical
项目研究机构: Corixa (Originator)
合成路线:The reaction of the glucopyranosyl bromide (I) (or its chloride analogue) with the N-acyl-L-serine benzyl ester (II) by means of Ag-OTf in dichloroethane gives the glucoside (III),which is deprotected at the amino group with Zn and AcOH yielding the 2-aminoglucoside (IV).The condensation of (IV) with the tetradecanoic acid (V) by means of EDDQ in dichloromethane affords the amide (VI),which is finally deprotected by hydrogenation with H2 over PtO2 in THF/AcOH.

合成路线:The intermediate,the glucopyranosyl bromide (I) has been obtained as follows: The reaction of 2-(trimethylsilylethyl)-2-amino-2-deoxy-4,6-O-isopropylidene-beta-D-glucopyranoside (VII) with Troc-Cl and NaHCO3 gives the N-protected glucoside (VIII),which is acylated with the tetradecanoic acid (IX) by means of EDC and 4-(1-pyrrolidinyl)pyridine in dichloromethane to yield the 3-O-acylated glucoside (X).The hydrolysis of the isopropylidene group of (X) with AcOH affords the diol (XI),which is selectively protected at the primary OH group with 2,2,2-trichloro-1,1-dimethylethyl chloroformate (XII) in pyridine to provide (XIII).The phosphorylation of the remaining OH group of (XIII) with diphenyl chlorophosphate (XIV) by means of DIEA in dichloromethane gives the phosphoric ester (XV),which is finally desilylated and hydrolyzed with TFA in dichloromethane,and treated with oxalyl bromide in dichloromethane/DMF to furnish the target glucopyranosyl bromide (I).

合成路线:The intermediate,the N-acyl-L-serine benzyl ester (II) has been obtained by N-acylation of L-serine benzyl ester (XVI) with the tetradecanoic acid (V) by means of EDDQ in dichloromethane.

合成路线:The reaction of the glucopyranosyl bromide (I) (or its chloride analogue) with the N-acyl-L-serinamide (II) by means of Ag-OTf in dichloroethane gives the glucoside (III),which is deprotected at the amino group with Zn and AcOH yielding the 2-aminoglucoside (IV).The condensation of (IV) with the tetradecanoic acid (V) by means of EDDQ in dichloromethane affords the amide (VI),which is finally deprotected by hydrogenation with H2 over PtO2 in THF/AcOH.

合成路线:The intermediate,the glucopyranosyl bromide (I) has been obtained as follows: The reaction of 2-(trimethylsilylethyl) 2-amino-2-deoxy-4,6-O-isopropylidene-beta-D-glucopyranoside (VII) with Troc-Cl and NaHCO3 gives the N-protected glucoside (VIII),which is acylated with the tetradecanoic acid (IX) by means of EDC and 4-(1-pyrrolidinyl)pyridine in dichloromethane to yield the 3-O-acylated glucoside (X).The hydrolysis of the isopropylidene group of (X) with AcOH affords the diol (XI),which is selectively protected at the primary OH group with 2,2,2-trichloro-1,1-dimethylethyl chloroformate (XII) in pyridine to provide (XIII).The phosphorylation of the remaining OH group of (XIII) with diphenyl chlorophosphate (XIV) by means of DIEA in dichloromethane gives the phosphoric ester (XV),which is finally desilylated and hydrolyzed with TFA in dichloromethane,and treated with oxalyl bromide in dichloromethane/DMF to furnish the target glucopyranosyl bromide (I).

合成路线:The intermediate,the N-acyl-L-serinamide (II) has been obtained by N-acylation of L-serinamide (XVI) with the tetradecanoic acid (V) by means of EDDQ in dichloromethane.