Synthesis of phosphonate and phostone analogues of ribose-1-phosphates

Abstract

SummaryThe synthesis of phosphonate analogues of ribose-1-phosphate and 5-fluoro-5-deoxyribose-1-phosphate is described. Preparations of both the α- and β-phosphonate anomers are reported for the ribose and 5-fluoro-5-deoxyribose series and a synthesis of the corresponding cyclic phostones of each α-ribose is also reported. These compounds have been prepared as tools to probe the details of fluorometabolism in S. cattleya.

Identification of a fluorometabolite from Streptomyces sp. MA37: (2R3S4S)-5-fluoro-2,3,4-trihydroxypentanoic acid

“…22 Oxidation of the anomeric alcohol to give lactone 20 was efficiently accomplished using iodine in DCM in the presence of potassium carbonate, 23 and then uorination with Deoxouor® afforded uorolactone 21 in good yield. 24 Acetonide hydrolysis using TFA in water gave 5-FRL 9 and nally hydrolysis was accomplished with aqueous LiOH to give 10. This synthetic 5-FHPA 10 was found to be identical by 19 F-NMR to the enzyme (FdrC) reaction product.…”

Syntheses of 1,2‐Oxaphospholane 2‐Oxides and 1,2‐Oxaphosphole 2‐Oxides

“…[44,45] Bicyclic ). [46] Following a similar procedure, trifluoro cyclic phosphonate analogs 92 of nucleoside 3'-phosphates were synthesized in 30-37 % yields from diethyl 2-(2-base-3-fluoro-4-hydroxytetrahydrofuran-4-yl)-1,1-difluoroethylphosphonates 91 via hydrolysis of phosphonate and esterification (Scheme 24). [7]…”

“…Bicyclic 1,2‐oxaphospholane 2‐oxides, (3a S ,5 R ,6 R ,6a R )‐5‐alkyl‐2,6‐dihydroxypentahydrofuro[2,3‐ d ][1,2]oxaphosphole 2‐oxides 90 as phostone analogues of ribose‐1‐phosphates, were synthesized in 40–47 % yields from diethyl (((3a R ,4 S ,6 R ,6a R )‐2,2‐dimethyltetrahydrofuro[3,4‐ d ][1,3]dioxol‐4‐yl)methyl)phosphonates 89 via dealkylation of phosphonate, deprotection of acetal, and esterification with acetic anhydride as dehydranting agent (Scheme 23). [46] …”

Synthesis of a C-phosphonate mimic of maltose-1-phosphate and inhibition studies on Mycobacterium tuberculosis GlgE

“…Synthesis of glycosyl C-phosphonates has been accomplished before for glucose and ribose monosaccharides. The most common routes for synthesis of such compounds comprise (i) a Horner-Wadsworth-Emmons approach that involves treating glycosyl donor 5 with tetramethyl methylene diphosphate 10 or (ii) a Michaelis–Arbuzov reaction between an anomeric halomethylene moiety and a trialkyl phosphite. We investigated both synthetic strategies in order to elaborate maltose into the desired target MCP 13 .…”