Of L-ribose

The synthesis of L-ribose required two significant innovations for its completion. The first was an efficient synthesis of diisopropyl (chloromethyl)boronate (1) via the in situ preparation of (chloromethyl)lithium by addition of butyllithium to a mixture of chloroiodomethane and triisopropyl borate in THF at — 78°C 18. 

Eclipsed conformation of L-ribose is oriented properly for ring closure. 

The mutarotation of ribose was first observed by Phelps, Isbell and Pigman47 48 who studied both the d- and L-isomers in aqueous solution at 1°. The mutarotation of L-ribose in water at 0°, shown in Fig. 1, is a complex one, due probably to the existence of equilibria involving both furanose and pyranose forms. There is considerable evidence to support this view. Bredereck, Kothnig and Berger26 found that, while the mutarotation of D-ribose in pyridine at 20° is complex, the mutarotation of 5-trityl-D-ribose (which can exist only in the furanose form) in pyridine at 3° is of the normal, first order type. Isbell and Pigman48... 

Two years after the first preparation of L-ribose, Fischer74 described the reduction of the sugar with sodium amalgam to the corresponding pentitol, which he showed to be identical with the polyol adonitol from Adonis vernalis L.75 76 A process for the catalytic hydrogenation of D-ribose in the presence of magnesium-activated Raney nickel to ribitol has been patented.77... 

Didesoxydihydrostreptose formed an acidic complex with boric acid. In accordance mth the extensive work of Boeseken and his students, this is indicative of a configurationally cis a-glycol grouping and the configuration of didesoxydihydrostreptose would be one of the two formulas shown (XLVII or XLVIII). Streptose itself would then have either the configurational system of L-ribose or L-lyxose and would... 

Crystalline L-altrose was described in 1934 by Austin and Humoller. After improving the methods for the preparation of L-ribose," they applied the cyanohydrin synthesis to 30 g. of that sugar and obtained 17 g. of crystalline calcium L-altronate and 14.5 g. of crystalline L-allono-7-lactone. Reduction of the latter with sodium amalgam yielded crystalline L-allose. The calcium L-altronate, by appropriate reactions, was converted to L-altrose, and the last of the sixteen theoretically possible aldohexoses had been prepared. Data on L-altrose and its derivatives are included in Table I. 

SCHEME 13.37 Synthesis of L-ribose with a polymer-supported glycoaldehyde anion equivalent... 

L-Nucleosides represent a class of nucleoside analogs with an excellent profile for antiviral activity combined with minimal host toxicity [105]. Synthesis of new L-nucleosides can use L-ribose and 2-deoxy-L-ribose as starting materials. Synthetic preparations of L-ribose from natural epimeric L-aldopentoses such as L-arabinose or L-xylose has recently been reviewed [106]. The simpler approach used an oxidation-reduction at C-2 from L-arabinose as depicted in Scheme 18 [107, 108]. 

Routes by asymmetric organocatalysis are available to account for the occurrence of chiral molecules on earth. L-proline and L-serine yielded relatively high values of ee in aldol condensations (Cordova et al. 2005). An epimer of a distinct amino acid, for instance, proline or serine, can serve as a catalyst in aldol reactions (Cordova et al. 2005). The percentage of the catalyzing amino acid determines the ee of the reaction product. Thus, the preferred formation of D-ribose compared to that of L-ribose can be accounted for by the intrinsic property of the reaction system with an asymmetric molecule acting as biocatalyst. L-proline has exceptional properties due to its structure, Fig. 3.3. 

Two useful syntheses of L-ribose represent applications of the benzoate inversion reaction. The protected L-arabinose derivative (57), on treatment with sodium benzoate in iV,iV-dimethylformamide for 72 hours at reflux temperature, gave a mixture that contained the monobenzoate (58) this could be further benzoylated to give a low overall yield of... 

Reaction of 2-amino-2-deoxypentoses with pentane-2,4-dione and 1-phenyl-butane-1,3-dione afforded substituted pyrroles (e.g., 41) and the riboflavin analogue (42) was prepared by condensation of l>-ribose with 5-amino-o-cresol, followed by cyclocondensation of the product with violuric acid. Reaction of dehydroascorbic acid with o-phenylenediamine followed by aroylhydrazides afforded compounds of the type (43), the side-chains of which have been further elaborated. The acid derived by oxidation of 2,3 4,5-di-0-iso-... 

Fig. 2. Mutarotation of L-ribose in water at 0°C. (Reprinted from J. Research Natl. Bur. Standards 18, 164 (1937))-...

Synthetic ribitol has been prepared by the reduction of L-ribose with sodium amalgam (28), Oddly enough, whereas L-ribose is a synthetic pentose, ribitol does not appear to have been prepared from the naturally occurring D-ribose. Lespieau (20, 29) and Raphael (21) have each obtained ribitol along with DL-arabitol in their syntheses from noncarbohydrate precursors, mentioned previously. 

The reaction of 1,3,2-dioxaborolanes with (dichloromethyl)lithium has wodced best when all substituents are nonpolar and nonbasic. It is probably the zinc chloride promoted rearrangement step that is most affected, since coordination of the zinc chloride with a nucleophilic site results in a sterically bulky complex that can inhibit the rearrangement of the intermediate borate anion. This coordination was noted early in our woiic, as increasing amounts of zinc chloride were required as the number of bem loxy groups increased during a synthesis of L>ribose (18). 

Following the general procedure used for the preparation of 48, a considerable variety of (alkoxyalkyl)boronic esters have been prepared. Scheme 8.12 illustrates the synthesis of L-ribose [38). Benzyl oxide substitution on pinanediol (chloromethyl)-boronate (49) yielded the benzyloxy derivative 50. Benzyl oxide substitution in the conversion of 50 into 51 worked best with the bromo intermediate derived from (di-... 

Chain extension using an insertion reaction of dichloromethyl-lithium or dibromomethyllithium with a cyclic chiral boronate derivative, (S)-pinanediol[(benzyloxy)methylJboronate (2), has been used in a synthesis of L-ribose in 13% overall yield (Scheme 3)- A new... 

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