Aldonolactones derivatives

As acylation of aldonolactones is related to -elimination reactions, the fully acylated aldonolactone derivatives are mentioned in Section IX (see also Sections VI and VIII). Only a few studies on selective acylation of aldonolactones have been described. The partially acylated derivatives have been employed as glycosylating agents or for the preparation of monometh-ylated sugars. 

Because of the activating effect of the carbonyl group, aldonolactone derivatives readily undergo -elimination reactions to yield unsaturated lactones. 

Related imino alditols such as azepanes or lactam derivatives have been obtained and have shown to be glycosidase inhibitors [96, 100]. Both d- and l-gulonolactone have been converted into polyhydroxylated 1,6-aldonolactams of type 79 in a sequence of straightforward functional transformations, including sulfinylation of the corresponding aldonolactone-derived acetonides 76 that gave 5,6-cyclic sulfites 77 (Scheme 23) [101]. The latter reacted with sodium azide... 

Scheme 23 Synthesis of di-hydroxylated 1,6-aldonolactams via aldonolactone-derived sulfites...

The aldonolactone derivative 838 also reacted with 5-lithiopyrimidines to give a mixture of the two hemiacetal C-nucleosides 986. Reduction of the latter with sodium borohydride and removal of the protective groups gave the corresponding acyclo analogs 893 (68JOC140) (Scheme 287). 

Substituted aldonolactones react with epoxides in the presence of boron trifluoride to give spiro-products which can otherwise be made from diols under dehydrating conditions. By these two approaches both simple products and disaccharide products, e.g. (13) and (14), were made. Aldonolactone derivatives also react under Reformatsky conditions to give keto-acid derivatives which are dealt with in the ulosonic acid section below. 

Condensation of the corresponding aldonolactone derivative with 1,1,1-tri-chlorotoluene and trimethyl phosphite gives the exo-alkenes 166 from which C-glycosides are available. Reaction of 0-substituted 1,2-0-isopropylidene-a-D-xylofuranose with allyltrimethylsilane and a Lewis add gives the 2-0-un-protected p-C-allyl C-glycosides. ... 

A further novel approach to aryl -glycosides starts with aldonolactone derivatives (Scheme 30), and another provided... 

A route to l,5-dideoxy-l,5-imino-D-xylonolactam has utilized a 5-azido-5-deoxy-aldehydo-T>-xylose derivative,and a route to C-glycosides by reaction of aldonolactone derivatives with alkyl lithiums followed by triethylsilane reduction is elaborated in Chapter 3. 

The volatility of the trimethylsilyl derivatives of the aldonolactones and related carbohydrates has made these derivatives suitable for use in mass spectrometry.161,162 Petersson and coworkers161,162 reported the mass spectra of a variety of trimethylsilyl derivatives of aldonolactones, including the spectrum of 54. 

Other derivatives of aldonolactones and alditols that have found some use in g.l.c. are trifluoroacetates156 and methyl ethers.163... 

The hydroxyl groups of aldonolactones react with a variety of aldehydes and ketones to give the corresponding acetal derivatives. Treatment of the salts of aldonic acids with benzaldehyde and hydrochloric acid or zinc chloride as catalysts give benzylidene derivatives of aldonic acids or aldonolactones (3). 

Reactions of acetal derivatives of aldonolactones involving the lactone carbonyl group or used as chiral precursors in the synthesis of noncarbohydrate natural products are discussed in later sections. 

Aldonolactones having their hydroxyl groups protected as ethers (mainly benzylated and silylated derivatives) have been employed for chain elongation through the carbonyl group, and therefore these type of derivatives are included in Section V. 

Addition of lithiated heterocycles to aldonolactones yields carbon-linked nucleosides (56). Thus, the reaction of 2,3 5,6-di-O-isopropylidene-L-gu-lono-1,4-lactone (9b) or 2,3-O-isopropylidene-D-ribono-l,4-lactone (16a) with various lithiated heterocycles gave gulofuranosyl derivatives 53a-g or ribofuranosyl derivatives 54b,c. Gulonolactols 53a-g and ribonolactols 54b,c were acetylated with acetic anhydride in pyridine to yield their acetyl derivatives. The stereochemistry of compounds 53a-g and 54b,c was discussed in terms of the Cotton effect of circular-dichroism curves of the ring-opened alcohols formed upon reduction by sodium borohydride. The configuration at C-l of 53g was proved by means of X-ray analysis (57,58). 

Similar addition of other lithiated thio derivatives to substituted aldonolac-tones has been performed (69). Thus, reaction of tris(methylthio)methyl-lithium to benzylidenated or isopropylidenated aldonolactones, followed by mercury(II)-catalyzed desulfuration, led to derivatives of glyc-2-ulosonic acids. 

The Tebbe reagent [//-chloro-bis(cyclopentadienylXdimethylalumin-ium)-/r-methylenetitanium] in its pure, crystalline (70,71) or crude (72) forms has been employed for the methylenation of aldonolactones. Thus, D-ribono- 1,4-lactone derivatives 71a and 71b reacted with Tebbe s reagent to give (70,71) the exo-methylene compounds 72a and 72b. 

Difluoromethylenation (79,80) of aldonolactones may be readily accomplished by treatment of the lactone derivative with tris(dimethyl-amino)phosphine, dibromodifluoromethane, and zinc in refluxing tetrahy-... 

The acid-catalyzed acetalation of aldonolactones with alkyl acetals of aldehydes or ketones takes place, in some instances, with esterification of the lactone group to give acetal derivatives of alkyl aldonates (11,22). 

The procedure was proved to be general for the preparation of protected hydroxy acids from lactones (121). This apparently trivial process is often difficult to carry out, as the attempted derivatization of y or J-hydroxyacids frequently results in relactonization rather than hydroxyl protection. The method was applied to several aldonolactones to produce the corresponding intermediate hydroxyamides. Protection using [(2-trimethylsilyl)-ethoxy]methyl chloride, methoxymethyl chloride, ter/-butylchlorodimeth-ylsilane, or zm-butylchlorodiphenylsilane followed by ozonolysis gave the protected N-(y- or <5-hydroxyacyl)indole derivatives. Mild saponification gave indole and the acetal- or silyl-protected hydroxy acids. 

Sugar lactones react readily with hydrazine to give crystalline derivatives useful for isolation and identification (127). Thus, addition of hydrazine to a reaction mixture containing an aldonolactone facilitates isolation of the product. The lactone may be regenerated from the hydrazide by treatment with nitrous acid (128). The phenylhydrazides obtained on treatment of aldonolactones with phenylhydrazine are also useful for characterization (129,130). 

Reduction of aldonolactones and their derivatives with isotopically modified reducing agents leads to sugars labeled at the anomeric center. Glycosides substituted with deuterium or labeled with tritium are widely employed for kinetic isotope-effect measurements, mechanistic studies, isotope-tracing experiments, and so on. 

The regio- and stereo-selective functionalization of aldonolactones yields optically active lactones, which are important precursors in natural product synthesis. Concepts such as chiral templates and chirons, derived from carbohydrates, have been ingeniously and widely applied in synthesis (233). Among the commercially available aldonolactones, D-ribono-1,4-lactone is... 

Synthetic Uses of y-Butenolides Derived from Aldonolactones... 

Borchardt and coworkers (265) have employed the chiral cyclopenten-ones derived from aldonolactones for the synthesis of the analogue 302a of neplanocin A. Neplanocin A (302b) and aristeromycin (303), carbocyclic analogs of adenosine having antiviral and antitumor activities, have also been synthesized (277,278). 

Methyl oxetane-2-carboxylate derivatives (e.g., 284), obtained by ring contraction of aldonolactones, have been employed for the synthesis (279) of the nucleoside / -noroxetanocin [9-(/ -D-eryt/iro-oxetanosyl)adenine, 304] and its a-anomer via an a-chloride obtained by a modified Hunsdiecker reaction. Displacement of chloride by adenine and debenzylation gave 304. The threo isomer of304, /J-epinoroxetanocin (305), was likewise synthesized from D-lyxono-1,4-lactone. The oxetane nucleosides display potent antiviral activity against the human immunodeficiency virus (HIV). 

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