Nucleosides. Part LX. Synthesis and Characterization of Monomeric Cordycepin‐Vitamin and Cordycepin‐Lipid Conjugates Model Substances for Biodegradable Ester and Carbonate Linkages in Conjugates and Potential Inhibitors of HIV‐1 Replication

Abstract

Monomeric 3'-deoxyadenosine (cordycepin) was modified at the 2-0 -(13-18) and S'-O-position (25-29) by the vitamins E, D,, and A and by the two lipids 1,2-di-O-palmitoylglycerol and 1,2-di-O-hexadecylglycerol via succinate or carbonate linkages. These base-labile conjugates afforded protection groups like the 2-(4-nitropheny1)ethoxycarbonyl (npeoc) and monomethoxytrityl group (MeOTr) that are cleavable without harming the ester and carbonate bonds, respectively. Monomeric conjugates of cordycepin and vitamin E, vitamin D,, 1,2-di-0-palmitoylglycerol, and 1,2-di-O-hexadecylglycerol (see 13, 14, 17, 18, 25, 26, 28, and 29) inhibited HIV-l-induced syncytia formation 1.7 to 6.2 fold compared to 1.5-fold for cordycepin (see Table); ICsO values for 25 and 28 were 257 and 267 p~, respectively. In addition, the monomeric cordycepin-vitamin and -lipid conjugates inhibited HIV-1 RT activity 2 8 4 9 % which compares with a 13% inhibition of HIV-1 RT observed for cordycepin. The minimal inhibition of HIV-I-induced syncytia formation and HIV-1 RT activity did not proceed by the activation of RNase L. The monomeric conjugates tested (13, 14) increased PKR expression.

Reducible Amino Acid Based Cationic Lipids as Highly Efficient and Serum‐Tolerant Gene Vectors

“…α‐Tocopheryl chloroformate ( 2 , 4 mmol) in CH 2 Cl 2 (20 mL) was added dropwise to a solution of cystamine (10 mmol) and triethylamine (4 mmol) in CH 2 Cl 2 (100 mL) and stirred at room temperature for 24 h. The mixture was then washed with water (50 mL) and saturated brine (50 mL). The organic phase was dried over Na 2 SO 4 , filtered, and concentrated to afford a yellow oil, which was purified by column chromatography on silica gel (CH 2 Cl 2 /MeOH 20:1, v/v) to yield 3 as light yellow oil (608 mg, 50 %).…”