Sugar phosphonates

Furthermore, the GPO procedure can also be used for a preparative synthesis of the corresponding phosphorothioate (37), phosphoramidate (38), and methylene phosphonate (39) analogs of (25) (Figure 10.20) from suitable diol precursors [106] to be used as aldolase substrates [102]. In fact, such isosteric replacements of the phosphate ester oxygen were found to be tolerable by a number of class I and class II aldolases, and only some specific enzymes failed to accept the less polar phosphonate (39) [107]. Thus, sugar phosphonates (e.g. (71)/(72)) that mimic metabolic intermediates but are hydrolytically stable to phosphatase degradation can be rapidly synthesized (Figure 10.28). 

Figure 10.28 Complementary routes for the stereoselective synthesis of hydrolytically stable sugar phosphonates, either from the bioisosteric phosphonate analog of DHAP or from phosphonylated aldehydes.

Tronchet, J.M.J., Neeser, J.-R., Gonzalez, L., and Charollais, E.J., Preparation of unsaturated sugars phosphonates using nucleophilic conjugate addition, Helv. Chim. Acta, 62, 2022, 1979. 

A convenient synthesis of 2-furylsugais starting from readily available sugar phosphonates and TBDPS-protected glycolaldehyde has been reported <99SL313>. 

Scheme 2.2.S.7 Synthesis of sugar phosphonic acids as potential enzyme inhibitors.

M. Mach and S. Jarosz, Reaction of sugar phosphonates with sucrose aldehydes. Synthesis of higher analogues of sucrose, J. Carbohydr. Chem., 20 (2001) 411 —424. 

H. Paulsen, W. Bartsch, and J. Thiem, Phosphorus-containing carbohydrates. III. Preparation of sugar phosphonates by Wittig and Horner reaction, Ber., 104 (1971) 2545-2552. 

Paulsen, H., and Bartsch, W., Phosphorus-containing carbohydrates. Part 12. Preparation of olefinic sugar phosphonates and allenic sugar phosphonates, Chem. Ber., 108, 1732, 1975. 

Recent improvements in the standard synthetic procedure using haloacetates have featured the use of trialkyi phosphites and activated acetates in the presence of trimethylsilyl trifluoromethanesulfonate (TMSOTf) as activating reagent. " This reaction has proved to be of great value in constructing complex sugar phosphonates. For example, in the presence of TMSOTf, the Michaelis-Arbuzov reaction between protected ketose acetates and triethyl phosphite takes place in ( 1 FC F at room temperature to produce, after deprotection, the expected diethyl l-(methoxycarbonyl)alkyl-phosphonates in high yields. -" ... 

Addition of dialkyl phosphites to 3-nitro-2,3-dideoxyhexenopyranose (11 ), or 1,2-dideoxyhexenopyranose (12) gives rise to phosphonates. An alternative route to sugar phosphonates involves the addition of dialkyl phosphites to 2-keto-sugars. ... 

Synthesis of sugar phosphonate analogs, which have attracted much attention for their potential bioactivity as inhibitors and regulators of metabolic processes (Guanti et al. 2000). These compounds are accessible by enzymatic aldolization of tu-diethylphosphonoylated- (3 -hydroxyaldehydes. 

Two sets of branched-chain sugar phosphonates, having the phosphonate attached to the C-3 branch carbon, have been synthesized, one such set being Illustrated in Scheme 3, and a variety of compounds of this type and related phosphinates and phosphine oxides... 

Unsaturated-sugar phosphonates have been obtained by the routes outlined in Scheme 110 " the trans-alktnc (313) underwent an allylic rearrangement on treatment with sodium ethoxide in ethanol to give the 1,2-dideoxy-sugar phosphonates (314) after hydrogenation/ ... 

FIGURE 10.16 Synthesis of higher sugar enones hy reaction of sngar aldehydes with stabilized sugar ylids or sugar phosphonates. 

Figure 16 Stereoselective synthesis of hydrolytically stable sugar phosphonates and 2-deoxv sun-ars based on DHAP analogs [106,107]. e p f ares ana z aeoxy sug...

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