Tagatose synthesis

D-Tagatose 6-phosphate is formed by liver phosphofructokinase acting on tagatose . Synthesis has been carried out starting with 1,2,3,4-diisopropylidene tagatose . 

Table sugar, sec Sucrose Tagatose, structure of, 975 Talose. configuration of, 982 Tamiflu, molecular model of, 130 Tamoxifen, synthesis of, 744 Till] DNA polymerase, PCR and, 1117 Tartaric acid, stereoisomers of, 305-306... 

Figure 10.15 Enzymatic one-pot synthesis of D-tagatose 1,6-bisphosphate based on the stereoselective TagA m coli.

An advantage of these enzymes is that they are stereocomplementary, in that they can synthesize the four possible diastereoisomers of vicinal diols from achiral aldehyde acceptors and DHAP (Scheme 4.2). Although this statement is generally used and accepted, it is not completely true since tagatose-l,6-bisphosphate aldolase (TBPA) from Escherichia coli-the only TBPA that has been investigated in terms of its use in synthesis-does not seems to control the stereochemistry of the aldol reaction when aldehydes different from the natural substrate were used as acceptors [7]. However, this situation could be modified soon since it has been demonstrated that the stereochemical course of TBPA-catalyzed C—C bond formation may be modified by enzyme-directed evolution [8]. 

Besides FDPA, three other aldolases using DHAP as the donor are known each aldolase generates a new C3-C4 bond with a different stereochemistry u-erythro for fuculose-l-phosphate aldolase, i.-threo for rhamnulose 1-phosphate aldolase, and D-erythro for tagatose 1,6-diphosphate aldolase [7]. These aldolases accept a great variety of electrophilic substrates, which has been widely exploited in synthesis of sugar analogues [8,9]. 

W. D. Fessner and O. Eyrisch, One-pot synthesis of tagatose 1,6-bisphosphate by diastereoselec-tive enzymatic aldol addition, Angew. Chem. lnt. Ed. Engl. 31 56 (1992). 

While the lyases that transfer a pyruvate unit form only a single stereogenic center, the group of dihydroxyacetone-phosphate-(DHAP, 41)-dependent aldolases create two new asymmetric centers, one each at the termini of the new C-C bond. A particular advantage for synthetic endeavors is the fact that Nature has evolved a full set of four stereochemically-complementary aldolases [189] (Scheme 6) for the retro-aldol cleavage of diastereoisomeric ketose 1-phosphates— D-fructose 1,6-bisphosphate (42 FruA), D-tagatose 1,6-bisphosphate (43 TagA), L-fuculose 1-phosphate (44 FucA), and L-rhamnulose 1-phosphate (45) aldolase (RhuA). In the direction of synthesis this formally allows the... 

In the synthesis of D-tagatose from the more common D-fructose, 1-O-benzoyl-2,3-O-isopropylidene-P-D-fructopyranose afforded two products identified as l-O-benzoyl-5-0-benzyl-2,3-0-isopropylidene-P-D-fructopyranose (97%) and its 4-O-benzyl isomer (2.8%). The skew-boat 6S4(D) conformation with an oxygen atom at C-5 adopting a quasi-equatorial position is responsible for the unexpected regioselectivity observed [136]. Conformational equilibria may also be a reason for the non-exclusive, though preferential substitution at 0-3 of benzyl 4-0-benzyl-6-deoxy-a-L-talopyranoside (9) [142]. Even in this case, however, no tri-O-benzyl derivative was formed and no starting material 9 remained, the total isolated yield of 10 and 11 being 87%. 

A synthesis of D-tagatose from D-galactose proceeds via the hexos-2-ulose derivative 212, which was obtained by oxidation under Moffatt conditions from 211 and exists as the tautomeric form 213.426... 

Eyrisch, O, Sinerius, G, Fessner, W-D, Eacile enzymic de novo synthesis and NMR spectroscopic characterization of D-tagatose 1,6-bisphosphate, Carbohydr. Res., 238, 287-306, 1993. Henderson, I, Sharpless, KB, Wong, C-H, Synthesis of carbohydrates via tandem use of the osmium-catalyzed asymmetric dihydroxylation and enzyme-catalyzed aldol addition reactions, J. Am. Chem. Soc., 116, 558-561, 1994. 

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