Novel phosphonylphosphinyl (P-C-P-C-) analogs of biochemically interesting diphosphates. Syntheses and properties of P-C-P-C-, analogs of isopentenyl diphosphate and dimethylallyl diphosphate

Abstract

There are numerous reports of phosphonate analogues of biologically interesting compounds.1 A related class of analogues

Phosphinophosphonates and Their Tris-pivaloyloxymethyl Prodrugs Reveal a Negatively Cooperative Butyrophilin Activation Mechanism

“…Previously, synthesis of compound 8 was reported from a phosphonylphosphonite, 22 while compound 10 was once claimed to have moderate phosphoantigen activity. 23 Our chemical synthesis of these HMBPP analogs is summarized in Scheme 1.…”

Synthesis of Analogues of Acyclic Nucleoside Diphosphates Containing a (Phosphonomethyl)phosphanyl Moiety and Studies of Their Phosphorylation

“…zov reaction between (phosphonomethyl)phosphonite and alkyl halide, [12] due to the poor yields of the synthesis of the starting phosphonomethyl-phosphonite, [27,15] which was accompanied by formation of side products and complicated separation. Isopropyl esters were used instead of ethyl esters to suppress side Arbuzov reactions with ethyl bromide.…”

“…[13] Farnesyl diphosphate analogues in which the diphosphate unit is replaced by a (phosphonomethyl)phosphanyl moiety showed inhibitory activity against squalene synthetase [14] and farnesyl diphosphate synthetase. [15] Glutamine synthetase inhibitors [16] and transcarbamoylase inhibitors [17] containing diphosphonate moieties have also been described.…”

Synthesis, inhibitory and activation properties of prenyldiphosphate mimics for aromatic prenylations with ubiA-prenyl transferase

“…Reduction of ketone 7 with NaBH 4 in MeOH produced β-hydroxy ester 8, which upon hydrolysis with LiOH in THF/H 2 O afforded the racemic β-hydroxy acid 3. The synthesis of the geranyl-based phosphonate 4 (Scheme 3) started with the Doering oxidation of geraniol to geranial (9), which was reacted with dimethyl methylphosphonate anion to give racemic 10. This methyl phosphonic ester was cleaved with trimethylsilyl bromide in the presence of 2,4,6-collidine as acid scavenger to afford the free hydroxyphosphonic acid 4.…”

“…These include phosphonophosphates, 8 phosphonophosphinates, 9 and diphosphonates, 10 where the methylene group replaces the oxygen between phosphorus and hydroxy-3,7,11-trimethyldodeca-2,6-dienyl diphosphate (6), i.e. oxidized FPP, was included.…”