L-threo isomer

The structure of the osazone derived from dehydroascorbic acid remains in dispute. Recently (Vol. 13, p. 95) it was described as the phenylhydrazine-phenylazo-structure (34), but it is now claimed that the bis(hydrazone) formula (35) fits the n.m.r. and u.v. data more satisfactorily. The structure of the bi-cyclic oxidation product of (35) has been shown to be a 3,6-anhydride (36) by n.m.r. and m.s. A n.m.r. study of the formation of dehydroascorbic acid hydrazones revealed that the two 2-phenylhydrazides (37) were formed initially and subsequently underwent dehydration to give the two rotationally isomeric 2-phenyIhydrazones. Reaction of 6-bromo-6-deoxy-isoascorbic acid (D-ery thro) with phenyl hydrazine afforded the cyclized bis(hydrazone) (38). Treatment of D-threo-ascorbic acid bis(phenylhydrazone) with caustic soda afforded the cyclized product (39). The corresponding D-erythro- and L-threo-isomers were also prepared and the side-chains have been modified in various ways. 

Efficient routes have been described for the synthesis of butenolide (13), its L-threo-isomer. and related compounds from L-ascorbic and D-isoascorbic acids. 1 ... 

Owing to the fully reversible equilibrium nature of the aldol addition process, enzymes with low diastereoselectivity will typically lead to a thermodynamically controlled mixture of erythro/threo-isomers that are difficult to separate. The thermodynamic origin of poor threo/erythro selectivity has most recently been turned to an asset by the design of a diastereoselective dynamic kinetic resolution process by coupling of L-ThrA and a diastereoselective L-tyrosine decarboxylase (Figure 10.47)... 

By this concept, a reversible enzymatic aldol reaction generates a mixture of l-threo/erythro aldol diastereomers (133) from which the i-threo isomer is preferentially decomposed by an irreversible decarboxylation to furnish aromatic aminoalcohol (R)-(134) vhth 78% ee in high yield. 

A consideration of the individual carbon atoms of the sugar chain thus leads to the conclusion that this trimethylglucose is the 2,3,6-isomer and ample confirmation of this conclusion has been forthcoming. To mention only two cases (a) oxidative degradation yields L-threo-di-methoxysuccinic acid,143 and (b) the sugar does not condense with acetone.130... 

Selenosulfonylation of olefins in the presence of boron trifluoride etherate produces chiefly or exclusively M products arising from a stereospecific anti addition, from which vinyl sulfones can be obtained by stereospecific oxidation-elimination with m-chloroper-benzoic acid134. When the reaction is carried out on conjugated dienes, with the exception of isoprene, M 1,2-addition products are generally formed selectively from which, through the above-reported oxidation-elimination procedure, 2-(phenylsulfonyl)-l,3-dienes may be prepared (equation 123)135. Interestingly, the selenosulfonylation of butadiene gives quantitatively the 1,4-adduct at room temperature, but selectively 1,2-adducts at 0°C. Furthermore, while the addition to cyclic 1,3-dienes, such as cyclohexadiene and cycloheptadiene, is completely anti stereospecific, the addition to 2,4-hexadienes is nonstereospecific and affords mixtures of erythro and threo isomers. For both (E,E)- and ( ,Z)-2,4-hexadienes, the threo isomer prevails if the reaction is carried out at room temperature. 

The synthesis proceeds from 37 through the intermediacy of 43 and 44. The glycoside derived from 45 and adriamycinone shows antitumor activity similar to that of the isomer adriamycin, but exhibits a much faster cellular uptake (1 ). Also, the an alternative to based on regioselective double-bond functionalization ( ). Thus, methyl 2,3,6-trideoxv-Q-L-threo-hex-2-enopyranoside (46), a key intermediate in the aforementioned procedure, is obtained from 11 upon reaction with Ph P=CHCHOCH CH, followed by controlled methanolysis. 

Ester enolates replace bromide from a-bromo boronic esters with remarkable diastereoselcctiv-ity. (Dibromomethyl)lithium is generated by addition of lithium diisopropylamide to dibro-momethane in the presence of a boronic ester at — 78 "C to produce an a-bromo boronic ester. Reaction of the a-bromo boronic ester with lithium 1-tert-butoxy-Tpropen-l-olate yields a product that is almost exclusively the threo-isomer (d.r. = 15 1 to 60 1), as shown by conversion to the / -hydroxy carboxylic ester24. It is worth noting the facility with which a-bromo boronic esters racemize in the presence of halide ions72. 

The (S)-leucine derivative (215) was allowed to react with diene (216) to afford the threo isomer (217) as the major product (d.s. = 80%) 213). Mukaiyama et al. 215) have reported the total synthesis of the sesquiterpene (-l-)-farnesiferol, starting from (R)-phenylglycinol, a derivative of the amino acid (R)-phenylglcine. They key step of this synthesis was an asymmetric Diels-Alder reaction. 

Addition ofbenzenethiol to 71 in the presence of a catalytic amount of tetrabutylammonium fluoride67 afforded only the trans isomer 7-(3,6-dideoxy - 2 - S - phenyl - 2 - thio -/ - l- erythro - hexopyranosyl- 4 -ulose)theo-phylline (105), In the absence of catalyst, 71 reacted with benzenethiol to give 7-(3,6-dideoxy-2-S-phenyl-2-thio-/ -L-threo-hexopyranosyl-4-ulose)theophylline (106). These results suggest that the uncatalyzed reaction gave the kinetic product, 106, whereas the catalyzed reaction led42 to the thermodynamic product 105. 

The results in Table VIII show that the selectivity with Co2(CO)8, although higher than that obtained with l-phenyl-2-methylpropene, is still very low. The aldehyde distribution is comparable with that for methyl tiglate. The main isomeric aldehyde is 27, and the erythro and threo diastereoisomers are formed in the same proportions. With rhodium the selectivity is very high, and the main aldehydes are 26 and 27. Twice as much threo isomer as erythro isomer is produced (14.2 and 8.4% ). 

With rhodium, aldehyde 27 is also the main isomeric aldehyde, but no aldehyde 26 is formed. Furthermore, slightly more erythro than threo isomer is formed. Thus, hydroformylation on / carbon is different for allylbenzene and for 3-phenyl-l-butene. The lower yield of 3-phenyl-2-methylbutanal is very likely the result of steric hindrance from the methyl group on the a carbon. 

The milder metal hydride reagents are also used in stereoselective reductions Inclusion complexes of amine-borane reagent with cyclodextrins reduce ketones to optically active alcohols, sometimes in modest enantiomeric excess [59] (equation 48). Diisobutylaluminum hydride modified by zmc broniidc-iV./V.A V -tetra-methylethylenediamine (TMEDA) reduces a,a-difluoro-(3-hydroxy ketones to give predominantly erythro-2,2-difluoro-l,3-diols [60] (equation 49). The threo isomers arc formed on reduction with aluminum isopropoxide... 

Addition of bromine in dichloromethane or of thioacetic acid in ethanol onto the methylene group of 9-arylidene and 9-carboxymethylene moieties of 6,7,8,9-tetrahydro-4//-pyrido[l,2-a]pyrimidines 546 stereoselectively gave 9-substituted 6,7,8,9-tetrahydro derivatives 547 and 548, respectively, at ambient temperature (Scheme 34) (90JHC247). Addition was also stereoselective with respect to the C(9) and C(9)—C centers, giving the erythro diastereomers as the primary products, which may then undergo epimerization to the threo isomers. The structure and epimerization of the products were studied by H and l3C NMR spectroscopy and by molecular mechanics calculations. 

Brenner et al.333 studied the isomerization of ascorbic acids. Epimerization at C-4 occurs in boiling 50% aqueous methanol containing potassium hydroxide, and an approximately equal mixture of epimers was obtained after 16-24 h. The rare l-erythro- and d-threo isomers of ascorbic acid were isolated as solids by fractional recrystallization of epimerized mixtures... 

Dibenzylidene-l,4-dimethyl-3,6-dihydro-2,5(1//,4//)-pyrazinedione (285) gave 3-benzylidene-6-(a-bromobenzyl)-6-hydroxy-l,4-dimethyl-l,4-dimethyl-3,6-di-hydro-2,5(l//, 4//)-pyrazinedionc (286) [NBS/H20—dioxane (— HOBr), 20°C, 12 h erythro and threo isomer, 50 and 33%, respectively, after separation],1030 also analogous reactions.1036... 

FDP A was employed in a study of pancratistatin analogs to catalyze the formation of the D-threo stereochemistry (Scheme 5.24). When rhamnulose 1-phosphate aldolase (Rha 1-PA) was used the L-threo stereoisomer was obtained with excellent selectivity. Thus these two enzymes allow the stereoselective synthesis of the two threo-stereoisomers [44]. They were also utilised successfully for the synthesis of different diastereoisomers of sialyl Lewis X mimetics as se-lectin inhibitors. Not only the two threo-selective aldolases RAMA and Rha 1-PA, but also the D-erythro-selective Fuc 1-PA was employed. In this way it was possible to synthesise three of the four diastereoisomers enantioselectively (Scheme 5.25). The L-erythro stereochemistry as the only remaining diastereo-isomer was not prepared [45]. This is because the aldolase that might catalyze its formation, TDP A, is not very stereoselective and therefore often yields mixtures of diastereoisomers. 

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