Three Threitol

For quality control, 100 pi pooled urine spiked with 8 pmol/1 sedoheptitol and 8 pmol/1 perseitol is included in each series. In addition, a 4 x dilution of this sample and a pooled urine spiked with 180 pmol/1 erythritol, 90 pmol/1 threitol, 218 pmol/1 arabitol, 36 pmol/1 xylitol, 18 pmol/1 ribitol, 36 pmol/1 sorbitol, 145 pmol/1 mannitol, 55 pmol/1 galactitol, 16 pmol/1 sedoheptitol and 16 pmol/1 perseitol are included in each series. These three urine samples were chosen to obtain concentrations in the low, middle and high part of the calibration curves. 

Chow and coworkers 40,41 reported the synthesis and characterization of homochiral dendrimers through the first generation by using (2R, 3i )-tartaric acid as the chiral building block. The mode of preparation is based on three parts the three-directional core, 1,3,5-trihydroxybenzene (61), the chiral connector, l-0-tosyl-4-terf-butyl-phenoxy-2,3-O-isopropylidene-L-threitol (62), and a branching unit, l-benzyloxy-3,5-dihydroxyben-zene (63). 

B. (+)-2-0-Benzyl-L-threitol.2a A 2-L, three-necked, round-bottomed flask is oven-dried (140°C) and flushed with nitrogen. The flask is equipped with an efficient mechanical stirrer, a 250-mL pressure-equalizing addition funnel, and a reflux condenser equipped with a mineral oil bubbler that is connected to a nitrogen source. 

Glyceraldehyde, of which 107 and 109 arc protected forms, is the only three-carbon sugar. There are two four-carbon sugars erythrose 111 and threose 113. Both exist in hemiacetal (furanose) and open chain forms and both are chiral but their symmetry properties differ. The tetrols formed by reduction of the aldehydes are me so erythritol 112 and C2 symmetric threitol 114 having the same stereochemistry as tartaric acid 35. Threose or threitol can be oxidised to tartaric acid. These sugars are the origin of the terms erythro and three sometimes used to describe such diastereomeric relationships. 

Threitol 114 has been used in many asymmetric syntheses, for example, the preparation of the C2 symmetric to-epoxide 117 by protection of the secondary and activation of the primary alcohols. Cyclisation of 116 could in principle give two fused four-membered rings, but three-membered rings are greatly preferred kinetically. The to-epoxide 117 reacts with nucleophiles at the terminal carbons.29... 

Synthesis from L-threitol The L-threitol derivative 24, obtained from D-(-)-diethyl tartarate in three steps and 90% overall yield, was used as a starting material for the synthesis of nectrisine (1) (Scheme 5). " Swern oxidation of 24 produced the L-threose derivative 25, which was transformed into the aminonitrile 26 in 96% overall yield from 24, as an inseparable diastereomeric mixture. Removal of the silyl protecting group from 26 followed by oxidation of the resulting primary hydroxyl group with TPAP afforded the lactam 27, which was treated with sodium methoxide to produce the methyl ester 28 in 62% yield from 26. Lithium borohydride reduction of 28 afforded a chromatographically separable mixture of the lactams 29 and 30 in a ratio of 56 44 and 87% total yield. Silylation... 

The bis-tosylate functionality in 47 is stable to mild acidic deketalization. The resulting (2 S, 35)-l,4-di-0-tosyl-L-threitol (52), when reduced with lithium aluminum hydride, provides 42, which has been converted in three steps to trans-(2S,3S)-Gpoxy mtsine (53) in an overall yield of 49% from 47 [25] (Scheme 13). 

The diversity associated with silyl protecting groups as well as the chemical conditions available for their removal makes them attractive alternatives to benzyl protection of the hydroxy groups of either D- or L-tartaric acid derivatives. O-isopropylidene-L-threitol (37) is mono-protected with er -butyldimethylsilyl chloride to furnish 266, which is converted in three steps to the nitrile 267. Reduction with DIBAL and Wittig olefination followed by desilylation with fluoride and Swern oxidation of the resulting alcohol provides aldehyde 268, which reacts with methyl 10-(triphenylphosphorane)-9-oxo-decanoate (269) to afford enone 270. Reduction of 270 with subsequent preparative TLC and acetal hydrolysis furnishes (9R)-271 and (9 S)-272, both interesting unsaturated trihydroxy Cig fatty acid metabolites isolated from vegetables [91] (Scheme 62). 

RNR activity is readily detectable in soluble cell-free extracts of S. shibatae, S. solfataricus, and P. furiosus, incubated with cytidine diphosphate (CDP), dithio-threitol (DTT), and adenosylcobalamin (AdoCbl), at high temperatures (70°-80°). Sodium acetate stimulates the activity and is included in the assay. Acetate probably acts as an allosteric effector. The activity is not air-sensitive and purification can be achieved aerobically at room temperature, reflecting the extreme stability of the enzyme. The activity can be purified 3000-fold in three steps (ammonium sulfate precipitation, phenyl-Sepharose and dATP-Sepharose chromatography) (Table I). The key purification step is affinity chromatography on dATP-Sepharose (400-fold purification), a method used successfully for the purification of several other RNRs.3i.32 Binding to this ligand is an indication that the thermophilic RNR is... 

Aldotetrose B must be D-threose because the alditol derived from it (o-threitol) is optically active (the alditol from D-erythrose, the other possible D-aldotetrose, would be meso). Due to rotational symmetry, however, the alditol from B (D-threitol) would produce only two NMR signals. Compounds A-F are thus in the family of aldoses stemming from D-threose. Since reduction of aldopentose A produces an optically inactive alditol, A must be D-xylose. The two diastereomeric aldohexoses C and D produced from A by a Kiliani-Fischer synthesis must therefore be D-idose and D-gulose, respectively. E and F are the alditols derived from C and D, respectively. Alditol E would produce only three C NMR signals due to rotational symmetry while F would produce six signals. 

The experimental work reported so far may be subdivided into two groups firstly, polycondensations based on nucleophilic monomers (which will be discussed first), and secondly, polycondensations involving electrophilic monomers. In principle, pentaerythritol, threitol or the methyl glycoside of glucose may be considered to be usefiil and relatively inexpensive b4 monomers. However, all these tetraols are poorly soluble in inert reaction media. Therefore, ethoxylated pentaerythritols ore the mercaptoacetate and mercaptopropionate were used (see Formula 12.6). Two versions of ethoxylated pentaerythritols (EPEs) are commercial and served as reaction partners of dicarboxylic acid dichlorides (DADs). The monomer called EPE-3 contains on the average three ethylene oxide units, whereas 15 ethylene oxide units are typical for EPE-15. 

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