Deblocking alkyl esters

Treatment of bromomethyl acetate with the sodium salt of a dialkyl phosphite, followed by deacetylation with methoxide affords the corresponding dialkyl hydroxymethanephosphonate. If this is tosylated with tosyl chloride, and the product treated with nucleosides [protected at the 3 -(and 2 -, if present) hydroxy groups] and sodium hydride in DMF, the monoalkyl ester of a 5 -0-phosphonyl-methyl nucleoside (60) is obtained after deblocking the sugar, and subsequent dealkylation with TMS-iodide affords (61). Like alkyl esters of 5 -mononucleotides, (60) is resistant to acid and alkaline hydrolysis, while (61) is stable in acidic and alkaline media, and is also resistant to hydrolysis by alkaline phosphomono-esterase and snake venom 5 -nucleotidase. Treatment of (61) with DCC and morpholine, and subsequently with orthophosphate or pyrophosphate, affords (62) and (63), respectively. Alkaline phosphomonoesterase from E. co/i hydrolyses the pyrophosphate links in (62) and (63) to give (61) and orthophosphate. The UTP and CTP analogues (63 B = U or C) are inhibitors of uridine kinase from... 

Spirapril (37) is a clinically active antihypertensive agent closely related structurally and mechanistically to enalapril. Various syntheses are reported with the synthesis of the substituted proline portion being the key to the methods. This is prepared fkim l-carbobenzyloxy-4-oxopro-line methyl ester (33) by reaction with ethanedithiol and catalytic tosic acid. The product (34) is deprotected with 20% HBr to methyl l,4-dithia-7-azospiro[4.4 nonane-8-carboxylate (35), Condensation of this with N-carbobenzyloxy-L-alanyl-N-hydroxysuccinate leads to the dipeptide ester which is deblocked to 36 by hydrolysis with NaOH and then treatment with 20% HBr. The conclusion of the synthesis of spirapril (37) follows with the standard reductive alkylation [11]. 

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