Chemistry of Sodium Borohydride and Diborane. IV. Reduction of Carboxylic Acids to Alcohols with Sodium Borohydride through Mixed Carbonic-Carboxylic Acid Anhydrides

Improvement of a Critical Intermediate Step in the Synthesis of a Nitroxide-Based Spin-Labeled Deoxythymidine Analog

“…The yield of the alcohol was 18% (or 66% based on recovered 1 and 4, Method 2). However, by using the conditions described by Ishizumi et al [7], reduction of 1 to 2 via 4 was achieved in 55% yield (Method 3).…”

Syntheses of 5‐Chlorouracils/Thymines with 1‐[Phosphono(Methyl/Difluoromethyl)]‐1,2‐Unsaturated‐Moiety‐Substituted Methyl Groups at N(1) and Human Thymidine Phosphorylase Inhibitory Activity

“…Compound 13 was dissolved in THF (15 ml) containing Et 3 N (2.18 ml, 15.66 mmol) and cooled to À 58. ClCO 2 Et (1.15 ml, 12.05 mmol) was added dropwise and the mixture was stirred for 30 min [27]. The precipitate was filtered off and washed with THF, and the combined filtrates were added dropwise to a stirred soln.…”

“…The carboxylic acid group in 13 was converted into an acyl carbonate derivative [27], then selectively reduced with NaBH 4 , to give allylic alcohol 14. Chlorination of 14 with the Appel [28] reagent generated from Bu 3 P/CCl 4 afforded 15, which was converted into 16 upon refluxing in P(OEt) 3 .…”

“…Compounds 8,12, and 16 all resonated as singlets in their MeOCO/Et functionalities into the corresponding allylic alcohols, served as substrates for the introduction of the pyrimidine moieties using the Mitsunobu reaction (Scheme 2). For this purpose, 3-benzoylthymine 3 ) [22] and 3-benzoyl-5-chlorouracil 4 ) (22; prepared by the same method as that used for 3-benzoylthymine [22] and its structure confirmed by X-ray-analysis [37] (27), 23% (30), 51% (31). e) 1.…”

Studies relating to the synthesis, enzymatic reduction and cytotoxicity of a series of nitroaromatic prodrugs

“…32 The alcohols 13 could also be prepared directly from the carboxylic acids 11 by formation of a mixed anhydride with ethyl chloroformate under basic conditions followed by NaBH4 reduction. 33,34 The required chloromethyl derivatives 8 were prepared from the alcohols 13 by their reaction with SOCl2 in CH2Cl2 solution at reflux. The series of prodrugs 8 were assessed against the enzymes human NQO1 and E. coli NR and their specific activities (calculated by dividing the initial rate of reaction by the concentration of the enzyme used and quoted as µmoles of compound reduced per minute per mg of protein (µmol/min/mg)) have been compared to CB 1954 1 (Table 1).…”