KDO derivative

No phosphate was released when the fraction was treated with phosphomonoesterase, indicating the presence of a phosphoric diester. Hydrolysis of the unknown KDO derivative (1 M HC1 for 5 h at... 

Chemical Shifts and First-Order Coupling-Constants of the Protons at C-3 of Selected KDO Derivatives (90 MHz)" (Ref. 81)... 

Anomeric triphenylphosphonium salts have been used as well as phenylsul-fides,but in the latter case extra stabilization is necessary (see below). Anomeric nitrosugars, which have been extensively studied in C-glycosylation reactions by Vasella, will be covered in Sect. 2.2.1 and ester enolates derived from 3-deoxy-2-ketoulosonic acids (sialic acid and KDO derivatives), which bear a structural similarity to 2-deoxy pyranosides, will be covered in Sect. 4.4. Deprotonation of anomeric phenylsulfones has been discussed in Sect. 2.1.1 and additional transformations on closely related compounds are presented in Scheme 14 [20]. Alkylation of phenylsulfone 54 with epoxide 55 provides adduct 56 which eliminates benzenesulfinic acid at room temperature to give the C(l)-alkylated glycal 57 a similar elimination is also observed with adducts derived from... 

An aglyconic derivative of KDO, having 0-7 and 0-8 temporarily blocked, was required for the synthesis of the model disaccharide Koenigs-Knorr reaction of 3 with a suitable halide derivative of KDO would be expected to occur exclusively at the (equatorial) 0-4 while 0H-5, being axially-disposed and experiencing additional steric shielding by H-7, would be practically unreactive. X-ray crystal structure analysis of KDO derivatives (14, 15) has shown that H-7 is orient-... 

R = Bz), [a]D -8.2° (chloroform), into ), [oi]d +22° (chloroform). The yield was quantitative and the single product was easily isolated just by conventional extractive processing. Therefore, if we can protect the hydroxyl group at C-6 with another protecting group, such as trityl ether, it will be possible to examine the coupling with KDO derivatives on both C-3 and 6 positions. 

Scheme 5.13. Synthesis of sialic acid and KDO derivatives from hexose and pentose sugars, respectively. P = PC>32. ...

Based on the foregoing observations, dibutylstannylene acetals of 8-O-protected Kdo derivatives should display great selectivity for 0-4, an... 

Fig. 49.—Methylation of the dibutylstannylene acetal of a Kdo derivative in a sealed vessel.313...

Among various strategies towards ulosonic acids various acylation reactions are often used. They involve alditol derivatives as convenient substrates, and diverse acyl anion equivalents. Here belongs the synthesis of KDO, developed by Shiba et al. [84], By reaction of the triflate 67 with the lithiated 68, eight carbon atoms compound 69 was obtained (Scheme 17). Removal of O-acetyl residue with subsequent NBS promoted oxidative hydrolysis of the dithioacetal moiety resulted in the formation of KDO derivative 70. 

Applying analogous substrates and reaction sequence, KDO derivative 73 was produced in the form of thioglycoside (Scheme 18) [85]. 

An interesting approach towards KDO, KDN and Neu5Ac as well, utilized a protected cyanohydrine 80 as a versatile acylanion equivalent of alkyl glyoxylate. Its reaction with appropriate halogeno alditol, as it is depicted in Scheme 20, provided the alkylated product 81 in good yield [91]. Conversion of 81 into desired KDO derivative 83 was achieved via a-ketoacid 82, resulted from hydrolysis of cyano group with NHjaq. 

An original, and versatile route toward ulosonic acids has been recently elaborated by Wu et al. [103,104,105], It based on a simple introduction of a-keto acid moiety via propargylation of suitable monosaccharides derived aldehydes and subsequent oxidation of the terminal alkynes. As it is exemplified by preparation of KDO, coupling of 61 with 3-bromopropyne gave the a fr-adduct 139 (Scheme 30). Its bromination using NBS/AgNC>3 provided the bromoalkyne 140, which on reaction with KMnC>4 afforded the desired a-keto acid ester, easily convertible into the anomeric mixture of KDO derivatives 143. The yield of all intermediates were very high. 

An alternative approach to the stereocontrolled synthesis of ulosonic acids was based on nucleophilic acylation of 2,3 5,6-di-O-isopropylidene-D-mannose 173 with a glyoxylate carboanion [116] derived from the mercaptal glyoxylate (Scheme 37). As a result the corresponding thio-octulosonates 174 and 175 were formed in 76% yield. Both compounds were converted to 176 using NIS (or NBS) and then MeONa. Applying Barton procedure [117] 176 was deoxygenated at C-3 to afford KDO derivative 124. 

Quite recently, a new access to KDO from 1-thio-l, 2-O-isopropylidene acetal 196 has been reported [122]. Its condensation with 2-furoic acid, followed by the Tebbe methylenation afforded 198 (Scheme 42). Cyclization process was mediated by methyl triflate. Thus obtained 1-furano glycal derivative 199 was converted into KDO derivative 66 and its 2-deoxy-a-analog 200 in a reaction sequence shown in Scheme 43 [122]. 

Methanolysis of 199, followed by oxidative degradation of the furan ring proceeded smoothly, providing KDO derivative 66. Transformation of 199 into 2-deoxy-KDO required the hydrogenation in the first step leading after several transformation to the methyl ester of the resulted acid. 

Treatment of the NeuNAc derivative 40 with Stnl2 in ediylme ycol and THF gave stereoselectively the product 41 with an axial carboxymethyl groiqt. The same sdectivi was found in the reduction of the equivalent Kdo derivative, leading to 2-deoxy P-Kdo.34... 

In the area of ulosonic acid glycosides a stereospecific route to a-glycosides of KDO derivatives has been described (Scheme 9), and a related route involves addition of hydrogen chloride to the glycal, conversion of the adduct via the phenyl thioglycoside to the sulphone and C-l carboxylation of the latter. The products could be reduced to the ulosonic acid thioglycosides and... 

Deoxy-6-thio KDO derivatives (44) are available, as shown in Scheme 8, either by dehydration/hydrogenation of the known 6-thio KDO diacetonide (43) or by reductive hydrolysis of the unsaturated 3>deoxy-6-thio-octonic acid derivative (46) [an intermediate in the preparation of (43) from D-mannose, see Vol.23, Qi.ll, ref.5] with Zn/HOAc and intramolecular displacement of the activated 2-OH group of the saturated intermediate (45) by the C-6 sulfur... 

The 4-and 5-phosphates of KDO have been prepared as their O-allyl glycosides by phosphorylation of the 7,8-0-isopropylidene methyl ester and separation of the two regioisomers. Various methyl glycosides of KDO phosphorylated at 0-4 and alkylated at 0-5, as in the case of (43), have been made to assist in the identification of KDO derivatives isolated naturally. When the glycosidic link is hydrolysed, such compounds undergo elimination of phosphate, and, if possible, subsequent Michael-type intramolecular... 

Purified enzyme from Escherichia coli has been studied for its reactivity tvith homologous five-carbon phosphosugars to yield KDO derivatives, and tvith modified nucleophiles. Thus, the stereochemically distinct fiuoro-analogs of PEP (Z)- and ( )-31 could be separately condensed vith D-erythrose 4-phosphate to yield, stereospecifically, the corresponding (3S)-and (3R)-configured, fiuoro-substituted DAHP derivatives 32 and 33, respectively (Figure 5.18) [127]. This provides direct evidence that the enzyme catalyzes si face addition of the C-3 of PEP to the rc face of the acceptor aldehyde. 

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