Hydroxyurea Analogues of Fosmidomycin

Abstract

Benzyloxyureas (4) have been prepared by reactions of diethyl 3-benzyloxyamino-propyl-phosphonate (3) with isocyanates, potassium cyanate or 1,1’-carbonyldiimidazole / methylamine. Conversion of phosphonic esters 4 into phosphonic acids 6 by means of bromotrimethylsilane and catalytic hydrogenation of 4, 6 afforded the target compounds 5, 7.

Alkoxycarbonyloxyethyl Ester Prodrugs of FR900098 with Improved In Vivo Antimalarial Activity

“…Treatment of the aldehyde 2 with O-benzylhydroxylamine gave the oxime, which was then reduced without prior isolation with sodium cyanoborohydride and hydrochloric acid to yield the O-(benzylhydroxylamino)propylphosphonic acid diethyl ester 3 [6]. Acetylation to 4 and subsequent reaction of 4 with trimethylbromosilane [7] and hydrolysis of the re- sulting silylester with water yielded the O-benzyl protected FR900098 5.…”

Synthesis and Evaluation of α-Halogenated Analogues of 3-(Acetylhydroxyamino)propylphosphonic Acid (FR900098) as Antimalarials

“…9 A notable exception to this 'rule' is the inversion of the retrohydroxamate into a hydroxamate as proven by Rohmer and coworkers. 12, 14 A β-oxa analogue bearing an N-methylhydroxamate functionality showed even better DXR inhibiting properties, 15 Results hence we also envisaged the synthesis of α-fluoro hydroxamate 6.…”

Flavonoids: True or promiscuous inhibitors of enzyme? The case of deoxyxylulose phosphate reductoisomerase

“…The syntheses of multiple fosmidomycin derivatives to improve its pharmacological properties gave rather disappointing results. Among the tested analogues, only few have similar or slightly better inhibition potency [14][15][16][17][18][19].…”