D-tagatose 1,6-bisphosphate

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

D-fructose 1,6-bisphosphate 2 (FruA E.C. 4.1.2.13), D-tagatose 1,6-bisphosphate 4 (TagA E.C. 4.1.2.40), L-fuculose 1-phosphate 5 (FucA, E.C. 4.1.2.17), and L-rhamnulose 1-phosphate 4 (RhuA, E.C. 4.1.2.19). From previous studies, we have DHAP aldolases with all four possible specificities readily available, we have demonstrated their broad substrate tolerance for variously substituted aldehydes, and we have investigated their stereoselectivity profile with non-natural substrates [3-6]. 

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... 

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. 

P-D-tagatose 1,6-bisphosphate P-D-fructose 1-phosphate P-D-fructose 1,6-bisphosphate... 

The D-tagatose 1,6-bisphosphate aldolase (TagA EC 4.1.2.n) is known as a class I subtype involved in catabolism of lactose and D-galactose of different microorganisms but... 

Apparently, all DHAP aldolases are highly specific for the donor component 22 for mechanistic reasons [29]. For synthetic applications, two equivalents of 22 are conveniently generated in situ from commercial fructose 1,6-bisphosphate 23 by the combined action of FruA and triose phosphate isomerase (EC 5.3.1.1) [93,101]. The reverse, synthetic reaction can be utilized to prepare ketose bisphosphates, as has been demonstrated by an expeditious multienzymatic synthesis of the (3S,4S) all-cis-configurated D-tagatose 1,6-bisphosphate 24 (Fig. 13) from dihydroxyacetone 27, including a cofactor-dependent phosphorylation, by employing the purified TagA from E. coli (Fig. 13) [95,96]. 

---