Azido-2-hydroxypropanal

One of the most efficient methods for the generation of 2,5-dideoxy-2,5-iminogalactitol 16 relies on the fuculose-1-phosphate aldolase-catalyzed aldol condensation of 2-azido-3-hydroxypropanal with dihydroxyacetone monophosphate (Scheme 13.17). The same method, applied to (2/ )-2-azidopropanal R)-V7 and to (25 )-2-azido-propanal (5 )-17, allows for the preparation of 2,5,6-trideoxy-2,5-imino-D-allitol 18 and 2,5,6-trideoxy-2,5-imino-L-talitol 19, respectively [22]. 

Similarly, employing 2-azidoaldehydes as RAMA substrates allowed the preparation of polyhydroxylated pyrrolidines (Fig. 14.1-5)[38, 52> 53]. l,4-Dideoxy-l,4-imino-D-arabinitol1521 was synthesized from azidoacetaldehyde, and both (2R.5R)-1491 and (2S,5R)-bis(hydroxymethyl)-(3R,4R)-dihydroxypyrrolidine1531 were synthesized from racemic 2-azido-3-hydroxypropanal, respectively. In the latter case, the kinetic product of the aldol addition was transformed into the (2R,5R)-stereoisomer of the pyrrolidine, while the thermodynamic product gave the (2S,5R)-stereoisomer. Furthermore, pyrrolidines structurally related to GlcNAc have been prepared ster-eoselectively by a similar transformation from lipase-resolved aldehyde precursors [541. 

Various pyrrolidines were prepared by using the chemoenzymatic approach. Thus, 2R,5S-dihydroxymethyl-3R,4A -dihydroxypyrrolidine (3) was prepared from the L-sorbose derivative 36 (Scheme 6). Thus, periodate oxidation of 2-azido-2-deoxythreitol (34) led to 2-azido-3-hydroxypropanal (35), which was treated with DHAP and FDP aldolase to... 

Deoxy-L-gaIactose-l-phosphate aldolase-catalysed reaction of dihydroxyacetone phosphate with 2-azido-3-hydroxypropanal, followed by a phosphatase and l drogenation, gives the 2,5-dideoxy-2,S-imino-alditol 54 as an a-galacto dase inhibhor. ... 

Compounds (9) and (10) have also been synthesized by an enzyme-catalysed process as indicated in Scheme 5 1,4-dideoxy-l,4-imino-D-arabinitol was also made from the same azido-hydroxypropanal using... 

Azido-2-hydroxypropanal 5-azido-5-deoxy-D-t/ireo-pentulose 71 TK 56... 

Two potent glycosidase inhibitors, (—)-l-deoxymannonojirimycin (—)-7 and (+)-l-deoxynojiri-mycin (+)-8, are readily obtained in three steps utilizing RAMA as a catalyst in the key C-C bond forming step [22,30]. From racemic 3-azido-2-hydroxypropanal and dihydroxyacetone monophosphate (DHAP), diastereomeric 6-azidoketones are formed. Following the acid phosphatase-catalyzed removal of phosphate and subsequent reductive amination (Scheme 13.15), the products are isolated in a 4 1 ratio favoring the manno derivative. A similar result is obtained with... 

A 1 4 mixture of deoxynojirimycin and deoxymannojirimycin was obtained when racemic 3-azido-2-hydroxypropanal was used as a substrate for RAMA[38> 39], indicating that the D-aldehyde is a better substrate for the enzyme. A similar result was obtained with FDP aldolase from E. coli,27 Since both deoxynojirimycin and... 

A chemoenzymatic synthesis of 1-deoxynojirimycin (2) was started by the condensation of DHAP and 3-azido-2-hydroxypropanal (104) catalyzed by the enzyme FDP aldolase to give 105 and 106 (Scheme 20). " Removal of the phosphate was catalyzed by phosphatase, followed by hydrogenation of the mixture over palladium on carbon to give a 4 1 mixture of 2 and its manno analogue. 

The ntfaesis of 1,5-dideoxy-l, S-imino-L-mannitol 26 and -L-rhamnitol 27 by the L>rhamnulose l-phoq>hate aldolase-catalysed reaction of dihydroxyacetone phosphate and 3-azido-2-hydroxypropanal, followed by hydrogenolysis and phosphatase treatment, has been described. ... 

Acetaldehyde (132 mg, 3 mmol) and D-(R)-3-azido-2-hydroxypropanal (115 mg, 1 mmol) were dissolved in 0.1 m triethanolamine buffer, pH 7.3 (10 mL) containing EDTA (1 mM). To this solution, RibA (400 units, available from Sigma-Aldrich) was added. The resulting solution was stirred in the dark for 2 days under N. The reaction was quenched by adding 2 volumes of acetone. The mixture was then incubated in ice for 20 min and centrifuged to remove the precipitated enzyme. After removal of the solvent under reduced pressure, the residue was purified by silica gel chromatr aphy (ethyl acetate/hexane (2 1), 0.12) to give the title compound (0.76 mmol, 76% yield). 

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