As one of the earliest developed antimicrobial classes, sulfonamides remain important therapeutic... more As one of the earliest developed antimicrobial classes, sulfonamides remain important therapeutic options for the empiric and definitive treatment of various infectious diseases. In the general population, approximately 3–8% of patients are reported to experience a sulfonamide allergy. Sulfonamide allergies can result in various physical manifestations; however, rash is reported as the most frequently observed. In patients with human immunodeficiency virus (HIV), dermatologic reactions to sulfonamide antimicrobial agents occur 10 to 20 times more frequently compared to immunocompetent patients. This article describes the incidence, manifestations, and risk factors associated with sulfonamide allergies. The potential for cross-reactivity of allergies to sulfonamide antimicrobials with nonantimicrobial sulfonamide medications is also reviewed. Data suggest that substitutions at the N1 and N4 positions are the primary determinants of drug allergy instead of the common sulfonamide moiet...
Long past the historical “golden era” of antibacterial drug discovery, the modern “resistance era... more Long past the historical “golden era” of antibacterial drug discovery, the modern “resistance era” is being countered by new legislation and advances in the rational design of antibacterial agents.
Abstract We devised a synthetic scheme based on a Horner–Wadsworth–Emmons olefination followed by... more Abstract We devised a synthetic scheme based on a Horner–Wadsworth–Emmons olefination followed by a stereoselective reduction in the attempt to synthesize a puromycin analog that cannot be metabolized to a known nephrotoxic 3′-aminonucleoside. This procedure allowed the synthesis of a fully protected nucleoside precursor of the target molecule. However, the last step proceeded with a surprising outcome, providing a dimethyl amide instead of the expected amino ketone derivative.
Page 203. CHAPTER 3 OXATHIOLANE AND DIOXOLANE NUCLEOSIDES: SYNTHESIS AND ANTIVIRAL ACTIVITY GIUSE... more Page 203. CHAPTER 3 OXATHIOLANE AND DIOXOLANE NUCLEOSIDES: SYNTHESIS AND ANTIVIRAL ACTIVITY GIUSEPPE GUMINA, JOHN S. COOPERWOOD and CHUNG K. CHU 3.1. Introduction Before the emergence ...
l,l-Puromycin, a diastereomer of the natural peptidyl nucleoside antibiotic puromycin, has been s... more l,l-Puromycin, a diastereomer of the natural peptidyl nucleoside antibiotic puromycin, has been synthesized from l-xylose in 13 steps.
Mesitonitrile oxide adds to polycyclic aromatic compounds (PACs) such as phenanthrene and pyrene ... more Mesitonitrile oxide adds to polycyclic aromatic compounds (PACs) such as phenanthrene and pyrene to give mono-cycloadducts. Pyrene does not afford bis-cycloadducts even when a large excess of 1,3-dipole is used. The more reactive benzonitrile oxide does not react with these PACs.
The target compounds were synthesized via the key intermediate carbohydrate 8, which was synthesi... more The target compounds were synthesized via the key intermediate carbohydrate 8, which was synthesized by first selectively protecting the 1'- and 2'-hydroxyl groups followed by selective tosylation of the 5'-hydroxyl group to obtain compound 3. The tosyl moiety was then replaced by a benzyl either to obtain 4. Compound 4 underwent Dess-Martin oxidation to afford the ketone 5. Compound 5 was subjected to Wittig olefination to afford the alkene 6 followed by regioselective hydroboration to obtain 7. Compound 7 was fully acetylated using acetic acid, acetic anhydride and sulfuric acid to obtain the key intermediate 8.
As one of the earliest developed antimicrobial classes, sulfonamides remain important therapeutic... more As one of the earliest developed antimicrobial classes, sulfonamides remain important therapeutic options for the empiric and definitive treatment of various infectious diseases. In the general population, approximately 3–8% of patients are reported to experience a sulfonamide allergy. Sulfonamide allergies can result in various physical manifestations; however, rash is reported as the most frequently observed. In patients with human immunodeficiency virus (HIV), dermatologic reactions to sulfonamide antimicrobial agents occur 10 to 20 times more frequently compared to immunocompetent patients. This article describes the incidence, manifestations, and risk factors associated with sulfonamide allergies. The potential for cross-reactivity of allergies to sulfonamide antimicrobials with nonantimicrobial sulfonamide medications is also reviewed. Data suggest that substitutions at the N1 and N4 positions are the primary determinants of drug allergy instead of the common sulfonamide moiet...
Long past the historical “golden era” of antibacterial drug discovery, the modern “resistance era... more Long past the historical “golden era” of antibacterial drug discovery, the modern “resistance era” is being countered by new legislation and advances in the rational design of antibacterial agents.
Abstract We devised a synthetic scheme based on a Horner–Wadsworth–Emmons olefination followed by... more Abstract We devised a synthetic scheme based on a Horner–Wadsworth–Emmons olefination followed by a stereoselective reduction in the attempt to synthesize a puromycin analog that cannot be metabolized to a known nephrotoxic 3′-aminonucleoside. This procedure allowed the synthesis of a fully protected nucleoside precursor of the target molecule. However, the last step proceeded with a surprising outcome, providing a dimethyl amide instead of the expected amino ketone derivative.
Page 203. CHAPTER 3 OXATHIOLANE AND DIOXOLANE NUCLEOSIDES: SYNTHESIS AND ANTIVIRAL ACTIVITY GIUSE... more Page 203. CHAPTER 3 OXATHIOLANE AND DIOXOLANE NUCLEOSIDES: SYNTHESIS AND ANTIVIRAL ACTIVITY GIUSEPPE GUMINA, JOHN S. COOPERWOOD and CHUNG K. CHU 3.1. Introduction Before the emergence ...
l,l-Puromycin, a diastereomer of the natural peptidyl nucleoside antibiotic puromycin, has been s... more l,l-Puromycin, a diastereomer of the natural peptidyl nucleoside antibiotic puromycin, has been synthesized from l-xylose in 13 steps.
Mesitonitrile oxide adds to polycyclic aromatic compounds (PACs) such as phenanthrene and pyrene ... more Mesitonitrile oxide adds to polycyclic aromatic compounds (PACs) such as phenanthrene and pyrene to give mono-cycloadducts. Pyrene does not afford bis-cycloadducts even when a large excess of 1,3-dipole is used. The more reactive benzonitrile oxide does not react with these PACs.
The target compounds were synthesized via the key intermediate carbohydrate 8, which was synthesi... more The target compounds were synthesized via the key intermediate carbohydrate 8, which was synthesized by first selectively protecting the 1'- and 2'-hydroxyl groups followed by selective tosylation of the 5'-hydroxyl group to obtain compound 3. The tosyl moiety was then replaced by a benzyl either to obtain 4. Compound 4 underwent Dess-Martin oxidation to afford the ketone 5. Compound 5 was subjected to Wittig olefination to afford the alkene 6 followed by regioselective hydroboration to obtain 7. Compound 7 was fully acetylated using acetic acid, acetic anhydride and sulfuric acid to obtain the key intermediate 8.
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