Enzymatic Resolution of Acetoxyalkenylphosphonates and Their Exploitation in the Chemoenzymatic Synthesis of Phosphonic Derivatives of Carbohydrates

Abstract

The resolution of racemic α‐, β‐, and γ‐hydroxy‐ω‐alkenylphosphonates was achieved by enzymatic hydrolysis of the corresponding acetates. The optically active alcohols were transformed into β‐hydroxyaldehydes and allowed to react with dihydroxyacetone phosphate (DHAP) via enzymatic aldol addition catalyzed by rabbit muscle fructose 1,6‐bisphosphate aldolase (FruArab). After enzymatic dephosphorylation, a set of novel sugar phosphonates was obtained.

Chemoenzymatic Synthesis of Racemic and Enantiomerically Pure Phosphaaspartic Acid and Phosphaarginine

“…This acid was first converted into the vinylacetyl chloride, then to the corresponding α‐ketophosphonate (Arbusov reaction with triisopropyl phosphite), which is reduced to the α‐hydroxyphosphonate with NaBH 4 . The diethyl analog of (±)‐ 6 was prepared by allylation of THP‐protected diethyl hydroxymethylphosphonate . This approach was not attractive as it comprised four steps and chromatographic purification.…”

“…The remaining ( R )‐chloracetate was extracted, purified, and chemically hydrolyzed in MeOH/Et 3 N. This time, the ee was determined to be 99 % by using ( R )‐(+)‐ tert ‐butyl(phenyl)phosphinothioic acid as chiral solvating agent and 31 P NMR spectroscopy. It is noteworthy, that Ganti et al needed 200 mg/mmol of lipase PL from Amano for the resolution of racemic diethyl 1‐acetoxy‐3‐butenylphosphonate and obtained an ee of 97 % in 24 h at 50 % conversion for the α‐hydroxyphosphonate …”

“…The diethyl analog of (±)-6 was prepared by allylation of THP-protected diethyl hydroxymethylphosphonate. [10] This approach was not attractive as it comprised four steps and chromatographic purification. The method used for the preparation of 5 by Kolyamshin et al was not attractive either as it involved chloromethyl allyl ether as starting material.…”

“…It is noteworthy, that Ganti et al needed 200 mg/mmol of lipase PL from Amano for the resolution of racemic diethyl 1-acetoxy-3-butenylphosphonate and obtained an ee of 97 % in 24 h at 50 % conversion for the α-hydroxyphosphonate. [10] Scheme 2. Lipase-catalyzed resolution of chloroacetate (±)-7.…”

Nonenzymatic kinetic resolution of racemic β-hydroxyalkanephosphonates with a chiral copper catalyst

“…The results are shown in Table 1. The selectivity s value 8 of a combination of Cu(OTf) 2 and (R,R)-Ph-BOX shown in Entry 1 was higher than those of other combinations (Entries 2-13). For instance, a combination of Zn(OTf) 2 and (R,R)-Ph-BOX promoted the benzoylation well, while the selectivity was somewhat low (Entry 2).…”