Threose synthesis

Synthesis from o-threose Synthesis of DABl (1) has been carried out by conversion of the D-threose derivative 33, readily available from D-(—)-diethyl tartrate, to the aminonitrile 34 as an inseparable diastereomeric mixture (Scheme 7). Subsequent deprotection with TBAF gave the alcohol 35 (quantitative). Esterification of 35 with p-toluenesulfonyl chloride afforded 36 (84%), which was treated with TFA-H2O-THF... 

Of course, with the drastic simplification inherent in the use of aldehyde 8 as the "real world" equivalent of the hypothetical threose 2, came the postponement of the goal of the synthesis of the natural enantiomer of NeuSAc. The only way to strive for enantiospecificity would involve replacing 7 with another diene equipped with a chiral auxilliary (111. At this exploratory stage, we preferred to accept a downscaling of goals, confident that lessons learned in the synthesis of racemic NeuSAc could be applied to the preparation of enantiomer 1 (synthesis of (-) NeuSAc has been accomplished DeNinno, M. P., Yale University, unpublished data). 

Further, convenient syntheses of the two fragments of Polyoxin J, deoxypolyoxin C and 5-0-carbamoylpolyoxamic acid, have been achieved in a highly stereoselective manner starting from the same chiral building block, 4-0-benzyl-2,3-0-isopropylidene-L-threose, leading to a formal total synthesis of Polyoxin J (36). 

M. Ruiz, T. M. Ruanova, O. Blanco, F. Nunez, C. Pato, and V. Ojea, Diastereoselective synthesis of piperidine imino sugars using aldol additions of metalated bislactim ethers to threose and erythrose acetonides, J. Org. Chem., 73 (2008) 2240-2255. 

The nitriles can also be employed as intermediates in the condensation of ethyl glyoxylate with aJdehydo sugars under the influence of sodium methoxide, leading to the preparation of L-ascorbic acid and similar compounds. Helferich and Peters described the synthesis of D-ascorbic acid (XXVIII) from tetraacetyl-n-xylononitrile (XXVI) presumably the nitrile underwent a type of ZempMn degradation and the n-threose (XXVII) thus formed condensed with the glyoxylic ester. The method... 

DL-Threonic acid (10) seemed to be a promising source of DL-threose. Therefore, other routes to 10 were elaborated. By a procedure consisting of five steps" 2-propenal (acrolein) — vinylglycoloni-trile — ethyl vinylglycolate — ethyl 4-bromocrotonate — 3-hydroxy-crotonic acid — 10, DL-threonic acid was obtained in an overall yield of 4.1%. Another synthesis of 10 was achieved17 in six steps starting... 

Compounds 11 and 12 were utilized for the synthesis of DL-threose and DL-erythrose, respectively. 

The direct homologation technique was then extended to the synthesis of various uncommon carbohydrate structures. Thus, higher sugars of the L-series were obtained Starting from 2,3-0-isopropylidene-4-O-benzyl-L-threose (43) [39c] (Scheme 13), and the amino tetrose 47 and pentose 48 were prepared from the a-amino aldehyde 46 derived from L-serine [46a] (Scheme 14). These amino sugars were used as chiral building blocks for the... 

L-Ascorbic acid has also been synthesized from D-galacturonic acid —a hexose derivative not so readily available as D-glucose. In addition, several methods have been reported for the synthesis of 1 starting with L-xylose (a pentose not readily available) and cyanide, or with L-threose (a tetrose not readily available) and a two-carbon fragment. 

Mukaiyama T, Suzuki K, Yamada T, Tabusa F (1990) 4-0-Benzyl-23-0-isopro-pylidene-L-threose a useful building block for stereoselective synthesis of monosaccharides. Tetrahedron 46 265... 

Considering the overall strategy adopted, what could be considered the main motive for using the D-threose derivative 2 in the synthesis ... 

What aldoses are formed when the following aldoses are subjected to the Kiliani-Fischer synthesis (a) D-threose (b) D-ribose (c) D-galactose ... 

Kusakabe, M, Sato, F, Stereoselective synthesis of D-erythrose and D-threose derivatives from D-glyceraldehyde acetonide and their reactions with l-(trimethylsiyl)vinyl cuprate reagent. Synthesis of allitol acetate, Chem. Lett., 1473-1476, 1986. 

Marshall, J A, Seletsky, B M, Luke, G P, Synthesis of protected carbohydrate derivatives through homologation of threose and erythrose derivatives with chiral y-alkoxy allylic stannanes, J. Org. Chem., 59, 3413-3420, 1994. 

In the presence of ZnBr2, nonchelation controlled addition of lithiated MN-dimethylacetamide to 2,3-O-cyclohexylidene-4-deoxy-i.-threose benzylimine proceeds in high stereoselectivity. The absence of the Lewis acid results in a slight preference for the other isomer. The product is used in the synthesis of l-daunosamine (equation 49). ... 

In a related synthesis (Scheme 9) diethyl oxopropanedioate (15) is condensed with the protected cyanohydrin of L-threose (14), producing L-ascorbic acid (27). This condensation presumably proceeds via the addition of anion 16 to 15 followed by hydrolysis and decarboxylation. Both of these synthetic approaches could be used in the preparation of L-ascorbic acid analogues. 

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