Acyloxymethyl as a drug protecting group. Synthesis and reactivity of N-acyloxymethylsulfonamide prodrugs

✍ Scribed by Teresa Calheiros; Jim Iley; Francisca Lopes; Rui Moreira

• Book ID: 103982917
• Publisher: Elsevier Science
• Year: 1995
• Tongue: English
• Weight: 213 KB
• Volume: 5
• Category: Article
• ISSN: 0960-894X
• DOI: 10.1016/0960-894x(95)00146-k

✦ Synopsis

Tertiary N-acyloxymethylsulfonamide prodrugs 3, encompassing penicillin and sulfonamide antibiotics, have been synthesised. The pH-independent hydrolysis of these compounds ocurrs via the rate-determining formation of an N-sulfonyl iminium ion. SCF-MO calculations using the PM3 method indicate that iminium ion formation is slightly favoured, when compared with the corresponding amides, by ca. 10 kJmo1-1.