Erythro/threo-4-Hydroxy

HOOC-CH-CH2-CO-COOH 1 OH Glutamin-Oxalo- essigsaure-Amino- transferase NH 1 HO2S— CH2—CH COOH HsO 20% 9 h erythro-... + threo-4-Hydroxy-glutaminsdure 43 43 98 98 4 vergl. 2... 

Alkylation of aldol type educts, e.g., /3-hydroxy esters, using LDA and alkyl halides leads stereoselectively to erythro substitution. The erythro threo ratio of the products is of the order of 95 5. Allylic and benzylic bromides can also be used. The allyl groups can later be ozonolysed to gjve aldehydes, and many interesting oligofunctional products with two adjacent chiral centres become available from chiral aldol type educts (G. Prater, 1984 D. Seebach, 1984 see also M. Nakatsuka, 1990, p. 5586). 

The aldol condensation of benzaldehyde with the thioacetamide carbanion (RCHCSNRV), derived from the desilylation of the silyl-thioether with tetra-/i-buty-lammonium fluoride, is stereoselective at—80°C producing the erythro isomer of the p-hydroxy thioamide preferentially (Scheme 6.18, R = Me, erythro threo 95 5) via a conformationally mobile intermediate. However, when R is bulky, a greater amount of the threo isomer is formed. Predictably, as the reaction temperature is raised, so the stereoselectively decreases. This procedure contrasts with the corresponding condensation catalysed by titanium salts, where the complexed intermediate produces the threo isomer [47, 48],... 

Asymmetric epoxidation, dihydroxylation, aminohydroxylation, and aziridination reactions have been reviewed.62 The use of the Sharpless asymmetric epoxidation method for the desymmetrization of mesa compounds has been reviewed.63 The conformational flexibility of nine-membered ring allylic alcohols results in transepoxide stereochemistry from syn epoxidation using VO(acac)2-hydroperoxide systems in which the hydroxyl group still controls the facial stereoselectivity.64 The stereoselectivity of side-chain epoxidation of a series of 22-hydroxy-A23-sterols with C(19) side-chains incorporating allylic alcohols has been investigated, using m-CPBA or /-BuOOH in the presence of VO(acac)2 or Mo(CO)6-65 The erythro-threo distributions of the products were determined and the effect of substituents on the three positions of the double bond (gem to the OH or cis or trans at the remote carbon) partially rationalized by molecular modelling. 

Figure 6 Structures of the four stereoisomers of sphingosine. Sphingosine has two chiral carbon atoms (C-2 and C-3). The Fischer projection formula of each structure is also shown, with C-1 at the top, to illustrate the D/L and erythro/threo stereochemical nomenclature. C-3 has an erythro orthreo configuration as it relates to C-2, depending on whether the similar groups (amino and hydroxy) are on the same or opposite side of the Fischer projection. D versus L refers to the configuration at C-2 relative to the configuration of D-glyceraldehyde versus L-glyceraldehyde.

In the presence of (Pj-LLB (3.3 mol%), the treatment of AT-phthaloyl-L-phe-nylalanal 17 with nitromethane at -40 °C gave practically a single stereoisomer of (2P,3S/)-2-hydroxy-4-phenyl-3-phthaloylamino-l-nitrobutane 18 in 92% yield (>99 1 eryf/zro-selectivity) [25]. Interestingly, reaction of the (S)-aldehyde 17 with nitromethane, using the (S)-LLB complex as a catalyst, led to a reduced diastereo- and enantioselectivity (96% yield erythro/threo 74 26 90% ee(eryth-ro)). The conversion of the nitroaldol adduct 18 into 19 was achieved in one pot (80% yield). 

H3C-C-C-COOC2H5 1 II Pt02 70%iges Athanol/ 1 20 erythro/threo-2-Amino-3 -hydroxy- 39 3... 

Treatment of 9 with various aldehydes gave the threo-3-hydroxy-ester after hydrolysis and esterification, in 90-95% diastereo-selectivity with enantiomeric excess of 77-85% (Table II). On the other hand, the boron enolate 10, when treated similarly with aldehydes now gave the erythro 3-hydroxy esters in 97-98% diastereoselectivity though in somewhat poorer ee s (40-60%,... 

Ipanguline Aj/isoipanguhne A, = erythro-/threo-l-0-phmy asx, y -9-0-(l, i- i-hydroxy-2-methylbutyryl)-platynecine... 

Ao = acetyl I An = angeloyl Ve = vera-troyl Va = vanilloyl HM.AB = erythro-2-hydroxy-2-methyl-3-aeetoxybutyryl MB = (l)-2-methyIbutyryl HMB = (d)-2-hydr-oxy 2-methylbutyryl t-DMB = d)-threo-2,3-dihydroxy-2-methylbutyryl e-DMB = (J)-ery[Pg.218]

Further work on the preparation of cryt/iro-2-alkyl-3-hydroxy-esters (140) by various condensations between propionic acid derivatives and aldehydes has been reported " the use of zirconium enolates seems to be particularly efficacious. Rules for predicting the stereochemical outcome of condensations between lithium enolates of esters and ketones and a-alkoxy-aldehydes have also been delineated. Pure erythro-isomer (140) can also be obtained in some cases by reduction of the corresponding jS-keto-ester with zinc borohydride. In related work it has been found that sodium borohydride in isopropanol reduces t-butyl a-alkoxy-j8-keto-esters to the corresponding -hydroxy compounds with erythro-threo ratios of between 2 1 and 20 1 in favour of the eryt/iro-isomer. In an extension of his previous work, Frdter has reported that dianions derived from cyclohexanol (141) can be alkylated with 95% stereoselectivity, to give (142). When the starting alcohol (141) is optically pure, a sequence of alkylation and oxidation leads to 2-ethoxycarbonylcyclohexanones with 76% enantiomeric enrichments. 

More modest asymmetric induction is obtained in the reactions of magnesium enolates of dihalogenoacetates with 2,3-O-isopropylidene-D-glyceraldehyde, which give P-hydroxy-esters with a ratio of erythro threo isomers of 7 3. ... 

Scheme 3.67 A stereodivergent route to threo- and erythro-S-hydroxy-y-lactones.

Following last year s report (2, 26) of the specific synthesis of erythro-3-hydroxy-2-methylcarboxylic acids, Buse and Heathcock have now developed a route to the corresponding threo-isomers by coupling aldehydes to allylic halides in the presence of chromium(ii) chloride followed by ozonolysis (Scheme 3). As in the previous study, use of an optically pure aldehyde e.g. (12)] leads to only two of the four possible diastereoisomers. 

Metabolism of P-hydroxy-a-amino acids involves pyridoxal phosphate-dependent enzymes that catalyze a reversible cleavage to aldehydes (Fig, 31) and glycine (89). The distinction between L-threonine aldolase (ThrA EC 4.1.2.5), L-a//o-threonine aldolase (EC 4.1.2.6), or serine hydroxymethyltransferase (SHMT EC 2.1,2.1) has often been rather vague since many catalysts display only poor capacity for erythro/threo (i.e., 91/90) discrimination [22]. Many enzymes display a broad substrate tolerance for the aldehyde acceptor, notably including variously substituted aliphatic as well as aromatic aldehydes (Fig. 31) however, a,P-unsaturated aldehydes are not accepted. 

A more eflicient and general synthetic procedure is the Masamune reaction of aldehydes with boron enolates of chiral a-silyloxy ketones. A double asymmetric induction generates two new chiral centres with enantioselectivities > 99%. It is again explained by a chair-like six-centre transition state. The repulsive interactions of the bulky cyclohexyl group with the vinylic hydrogen and the boron ligands dictate the approach of the enolate to the aldehyde (S. Masamune, 1981 A). The fi-hydroxy-x-methyl ketones obtained are pure threo products (threo = threose- or threonine-like Fischer formula also termed syn" = planar zig-zag chain with substituents on one side), and the reaction has successfully been applied to macrolide syntheses (S. Masamune, 1981 B). Optically pure threo (= syn") 8-hydroxy-a-methyl carboxylic acids are obtained by desilylation and periodate oxidation (S. Masamune, 1981 A). Chiral 0-((S)-trans-2,5-dimethyl-l-borolanyl) ketene thioketals giving pure erythro (= anti ) diastereomers have also been developed by S. Masamune (1986). 

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