L-Lactaldehyde derivatives

From Chiral Non-carbohydrates - A section on amino-sugars has been included in a review of the synthesis of monosaccharides from non-carbohydrate sources. L-Ristosamine 42 was synthesized by addition of the Cs-synthon 40 (which contains a masked aldehyde function that can be readily demasked by mild acid hydrolysis) to the L-lactaldehyde derivative 41 (Scheme 11). The TBSOP adduct 43 (Vol.27, p.ll4), derived from 2,3-< -isopropylidene-D-glycer-aldehyde, has been converted into 3-amino-3-deoxy-D-altrose 46 by a route involving cis-hydroxylation of its unsaturated lactam moiety and periodate cleavage between C-6 and C-7 of the derived heptitol derivative 45 as key steps (Scheme 12). 3-Amino-3-deoxy-L-allose was obtained by converting 43 to its C-3... 

Ethyl (S)-lactate has been the primary source of chirality in three amino-sugar syntheses. 2-Amino-2-deoxy-L-lyxonate (50) was almost the exclusive diastereomer formed when magnesium bromide was employed as the Lewis acid catalyst for the aldol condensation of L-lactaldehyde derivative (51) with silyl ketene acetal (52)... 

Ethyl (5 )-lactate has been the primary source of chirality in several syntheses of aminodeoxycarbohydrates. The derivative 91 of 2-amino-2-deoxy-L-lyxonic acid is the major product of condensation of 2-0-benzyl L-lactaldehyde with the silyl ketene acetal 90. The derived ester 91 can be converted into lactone 92 (Scheme 13.38) [79], an intermediate for the synthesis of L-daunosamine and L-vancosamine. 

The synthesis of antimycin A3 (676), a potent antifungal agent, makes use of lactaldehyde 658 to establish the stereochemistry of the three contiguous asymmetric centers in the eastern half of the dilactone skeleton via intermediate 678. Strategically, the 4,5-diphenyl-oxazole heterocycle is used as a template for protection of the latent activated carboxylate group, which is unmasked by photooxygenation [120,200]. The chiral western half of the dilactone framework is derived from the differentially protected L-threonine derivative 677. 

Aminoacid (o-threonine, L-aspartic) and hydroxyacid (L-tartaric, L-lactic) derivatives were repeatedly employed in the past as chiral substrates in the synthesis of daunosamine. More recently, protected L-lactaldehyde was used for the same purpose. Stereospecific synthesis of intermediate diol 95 was achieved with help of the enzyme (R)-hydroxynitrile lyase, which... 

From Chiral Non-carbohydrates. - The 3-amino-3,6-dideoxy-hexose derivative 50 was the major product obtained from aldol condensation of the tricarbonyliron-diene complex 47 with the (R)-lactaldehyde derivative 48 (Scheme 14). Adduct 49 was the major (45%) of four isomers formed. If decom-plexation (step iv) preceded reduction (step ii), then the 2-epimer of 50 predominated. IV-Acetyl-L-daunosamine and its 5-C-isobutyl analogue (52) were synthesized from the corresponding cyanohydrin derivatives 51 by chain extension (Scheme 15). Aziridination of chiral traws-a,p-unsaturated esters such as 53 gave mainly two isomeric 2,3-epimines, e.g. 54 and 55 in the ratio 67 33 (Scheme... 

A pertinent example of matched pairing is the reaction of ( S)-lactaldehyde 632 with a titanium derivative (640) of the bislactim ether of cyclo-(L-Val-Gly) [194]. In the transition state (641), the disposition of the chiral center (R group) of the aldehyde is favorable with respect to the heterocycle, whereas in a mismatched pair the R group and the H would be reversed, and the interaction would be unfavorable. Consequently, carbonyl attack follows the Felkin model and gives the anti isomer 642 with an anti syn ratio of 98.8 1.2. 

The preparation of MOM-protected lactaldehyde 658 parallels that of the MEM derivative. It can be obtained in a two-step sequence in which lactate 377 is initially reduced to the propanol 657 and then oxidized to the aldehyde under Swem conditions [199] or with Collins reagent [100]. Overall yields starting from ethyl L-lactate (2) average about 50%. Alternatively, ester 377 can be reduced directly to aldehyde 658 (52% yield) with diisobutyl-aluminum hydride at —78 °C [120,200]. 

Similar types of compounds (674) are available through a direct reaction of 658 with the vinylcarbonyl compounds 673 in the presence of a catalytic amount of DABCO (10 mol%) [202]. For both derivatives, the anti isomer (674) predominates to approximately the same extent (70 30). In the case of enone 673 (R=CH3), using l-azabicyclo[2.2.2]octan-3-ol instead of DABCO as the catalyst increases the yield of the reaction from 54% to 80%. If the syn configuration is desired, it is available from the reaction of lactaldehyde 464 with ketene acetals under chelation-coptrolled conditions (see compound 524, Section 1.5.1). 

Lactaldehyde 929 has been used in a synthesis of JV-benzoyl L-daunosamine (615), a derivative of the carbohydrate component of adriamycin [175] (Scheme 125). Two important reactions in the synthetic pathway are the conversions 929—> 930 and 933 935. The nitroaldol reaction of 929 with methyl 3-nitropropionate leads to a mixture of three isomeric adducts from which the major diastereomer 930 is separated by crystallization and chromatography. After lactonization and functional group adjustment, the hydroxyl stereocenter of the D-ribo lactone 933 must be inverted to match the correct configuration of the target sugar. This is accomplished by conversion to the mesylate 934 and subsequent treatment with sodium benzoate. The resulting h4yxo lactone 935 is then carried on to 615 as shown in Scheme 95 (Section 1.5.6.1). 

The first configurationally stable l-oxy-2-alkenyllithium 253 was reported in 1986 by Hoppe and Kramer [Eq. (70)] [8]. It was generated by deprotonation of the enantioenriched allyl carbamate 252, obtained fi om the corresponding alcohol via kinetic resolution through Sharpless epoxidation. More conveniently accessible are the 1-methyl derivatives 254 and analogues either from (R)- or (S)-lactaldehydes via Wittig olefination [154]. Kinetic resolution of rac-254 during deprotonation is also possible [155-157]. 

As part of a review on the use of metallated 2-alkenyl carbamates as chiral homoenolate reagents for asymmetric synthesis, the preparation of the a-D-allo cofigurated methyl-branched 3,6-dideoxy compound (56) as well as the fi-D-talo derivative (57) have been reported starting from R-benzyl lactaldehyde. For the preparation of the a-L-allo and the P-L-w/o compounds see Vol. 21, p.l44. 

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