Ribono-7-lactone

D-Ribono-1,4-lactone (1) readily condenses with acetone, under acidic catalysis with mineral acids or anhydrous copper sulfate, to give 2,3-0-isopropylidene-D-ribono-1,4-lactone (16a), which was employed for the synthesis of 5-deoxy and 5-0-substituted derivatives of D-ribono- 1,4-lactone and D-ribitol (24). Acid removal of the 1,3-dioxolane protecting group gave products having probable inhibitory activity of arabinose 5-phosphate isomerase (25). Other applications of 16a for the synthesis of natural products will be discussed later. 

Reaction of D-ribono-1,4-lactone with cyclohexanone catalyzed by Am-berlite IR-120 (H+) in refluxing benzene led to two products identified by their spectral data and chemical transformations as 2,3-O-cyclohexylidene-D-ribono- 1,4-lactone (16b) and 3,4-O-cyclohexylidene-D-ribono-1,5-lac-tone (17), obtained from the reaction mixture in 60 and 20% yields, respectively (27). 

The borohydride reduction-periodate cleavage applied to 2,3-O-isopro-pylidene-D-ribono- 1,4-lactone (16a) led to L-erythrose (30). The method was also employed (31) for the synthesis of D-erythrose, starting from an Obenzylidene-D-ribonolactone. However, in this case, the structural assignments for the intermediate compounds must be revised, as the starting material formulated as 3,5-O-benzylidene-D-ribono-1,4-lactone (2) was, as discussed previously in this section, the 3,4-0-benzylidene-D-ribono-1,5-lactone (3a). Therefore, the correct structure for the product described as 3,5-O-benzylidene-D-ribitol (20, not isolated) would be 3,4-O-benzylidene-... 

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. 

TV-Acyl indoles derived from amides have been employed for the conversion of lactones into protected hydroxyacids. Thus, (chloromethyl)alumi-num 2-(2-propenyl)anilide reacts (120) with 1,4- and 1,5-lactones, as for example per-O-terZ-butyldimethylsilyl-D-ribono-1,4-lactone (104), to afford hydroxyamides. After protection of the free hydroxyl group, these amides were converted by ozonolysis into TV-acyl indoles, 105, which were readily saponified to the acid 106. 

Polarographic (168) and electrochemical (169) procedures for the reduction of D-ribono-1,4-lactone have been developed, and the latter has been applied on a pilot-plant scale. 

The lactone derivative 158 obtained from D-ribono- 1,4-lactone afforded (—)-(i )-angelica lactone (159a) upon treatment with methanolic ammonia solution (6). In a similar way, Font and coworkers (207) synthesized (+)-(S)-... 

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... 

Numerous procedures for the preparation of butenolides have been developed. Font and coworkers (234-236) prepared the 5-O-substituted derivatives 223a-c of D-ribono-1,4-lactone. The cw-glycol system of223a reacted with ATjV-dimethylformamide dimethyl acetal and then with iodomethane to give the trimethylammonium methylidene intermediate 224. Pyrolysis of 224 gave the butenolide 225. 

D-Ribonolactone is a convenient source of chiral cyclopentenones, acyclic structures, and oxacyclic systems, useful intermediates for the synthesis of biologically important molecules. Cyclopentenones derived from ribono-lactone have been employed for the synthesis of prostanoids and carbocyclic nucleosides. The cyclopentenone 280 was synthesized (265) from 2,3-0-cyclohexylidene-D-ribono-1,4-lactone (16b) by a threestep synthesis that involves successive periodate oxidation, glycosylation of the lactol with 2-propanol to give 279, and treatment of 279 with lithium dimethyl methyl-phosphonate. The enantiomer of 280 was prepared from D-mannose by converting it to the corresponding lactone, which was selectively protected at HO-2, HO-3 by acetalization. Likewise, the isopropylidene derivative 282 was obtained (266) via the intermediate unsaturated lactone 281, prepared from 16a. Reduction of 281 with di-tert-butoxy lithium aluminum hydride, followed by mesylation, gave 282. 

The 2-trifluoromethanesuIfonates of the four diastereomeric 3,5-di-O-benzyl-pentono-1,4-lactones (such as D-ribono-1,4-lactone, 283) gave, upon treatment with potassium carbonate in methanol, the ring-contraction product, methyl oxetane-2-carboxylate (284). The stereochemistry at C-2 of the resulting oxetanes is determined by the configuration at C-3, rather than C-2, of the starting lactones (267). 

A number of enantiomerically pure chiral building-blocks, such as 292-294, have been prepared (270,271) by zinc-copper cleavage of 5-bromo-5-deoxy-2,3-0-isopropylidene-D-ribono-1,4-lactone, followed by reduction. Similarly, from the 5-iodo lactone analogue the enoic acid 295 was obtained by reaction with zinc/silver-graphite (272). 

A two-step sequence to prepare di-O-acetyl-3-deoxy-D-arabino-l, 4-lactone from tri-O-acetyl-D-ribono-1,4-lactone has also been reported, but in a low yield of 46% because ol the difficulty of controlling the elimination of the 3-acetoxy group, since the 2,3-unsaturated lactone also undergoes further elimination.5 Furthermore, partial racemization of the enolizable 2,3-unsaturated lactone could occur during treatment with DBU.6... 

Scheme 25 Synthesis of a A-alkylated aldonolactam from ribono-1,4-lactone...

Spirocychc C-ribosyl aromatic compounds have also been derived from o-ribono-1,4-lactone by a similar strategy. In this case a mild cylopentadienyl mthenium complex was used as catalyst for the cycloaddition step [114]. 

The question then arises if a regioselective opening of a 2,3-rraMS-epoxy carboxamide derived from aldonic acids would occur. The 2,5-di-O-tosyl-D-ribono-1,4-lactone (62) (Scheme 13) was used to find an answer to this question. If treated with ammonia, the 2,5-diamino-2,5-dideoxy-D-ribono-1,5-lactam (63) was obtained as the only product [79]. The NMR spectra of the reaction mixture showed the formation of the diepoxy amide A which was opened at C-5 by ammonia. In this case no internal lactamization could occur, due to the trans 2,3-epoxy group in B (Scheme 13). Thus, a regioselective opening of an acyclic 2,3-epoxy carboxamide took place at C-2. The reaction was complete within 6 days. 

Sasaki42 performed trcms-hydroxylation of trcm,y-2-hydroxy-3-pent-enoic acid (89) with 40% peroxyacetie acid, and obtained 5-deoxy-DL-arabinono-l,4-laetone (90) as the sole product. Jary and Kefurt41 repeated this experiment, and found that the reaction was not fully stereospeci-fie besides 90, 5-deoxy-DL-ribono- 1,4-lactone (91) was also formed. Reduction of the mixture of 90 and 91 with lithium aluminum hydride gave the corresponding 5-deoxy-DL-pentitols (92 and 93) in the ratio of 2.8 1. 

Obayashi and Schlosser [43] have briefly described syntheses of erythro-sphingo-sine and threo-sphingosine from D-mannose and D-ribono-1,4-lactone, respectively. For the synthesis of ery/Aro-sphingosine (35) D-mannose was converted into benzyl 2,3 5,6-di-O-isopropylidene-manno-furanosides and hydrolysis of the 5,6-0-iso-propylidene group followed by periodate oxidation and borohydride reduction and protection gave the methoxymethyl ether (28). This was converted into the chloride... 

For the synthesis of zAreo-sphingosine (40), D-ribono-1,4-lactone was converted into the protected derivative (36) which after reduction was converted into the chloride (37). This was converted via the 2,3-dihydrofurans (38) and (39), as described above for the synthesis of the erytAro-sphingosine, into the /Areo-sphingosine (40). 

Molecular oxygen in the presence of Pd/C catalyst and one equivalent of Mg(OH)2 affords the pentonolactones with >90% yield12 and is a useful method for the production of multigram quantities of D-ribono-1,4-lactone. Other noble metal catalysts have been used,11,13 some of them activated with other metals, such as gold or bismuth,14 as detailed in the following Chapter, by Varela, along with the kinetic studies performed. 

A similar approach, but using hydroxylation with osmium tetraoxide, was applied for the preparation of 2-C-methyl-D-xylono-1,4-lactone (114), 2-C-methyl-D-arabinono-1,4-lactone (115), 2-C-methyl-DL-lyxono-1,4-lactone (116, for the D isomer), and 2-C-methyl-DL-ribono-1,4-lactone (112 for the D isomer).297... 

F. J. Lopez-Herrera, F. Sarabia-Garcia, M. S. Pino-Gonzalez, and J. F. Garcia-Aranda, A new synthesis of 2-C-methyl-D-ribono-1,4-lactone and the C-9/C-13 fragment of methynolide, J. Carbohydr. Chem., 13 (1994) 767-775. 

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