Phosphonic derivatives of carbohydrates: chemoenzymatic synthesis

Enzymatic Resolution of Acetoxyalkenylphosphonates and Their Exploitation in the Chemoenzymatic Synthesis of Phosphonic Derivatives of Carbohydrates

“…Accordingly, when we carried out the same reaction using an excess of racemic aldehyde, we obtained a 4b:4a ratio of 2:1, with an overall yield of 50% based on FBP, which is the limiting agent. [1] In the case of aldehydes 2 and 3 we did not observe any appreciable difference in reactivity between the two enantiomers. It is worth noting that in these two cases no hydrolysis of the phosphonate group took place and only the diethyl esters have been isolated.…”

“…A possible explanation for this fact was already proposed in our preliminary communication. [1] It is based on an irreversi-ble intramolecular transphosphorylation carried out by the anomeric hydroxy, that is expected to be faster for the adduct 19b (corresponding to the final compound 4b) (Scheme 7). The resulting cyclic phosphonate 20b is no longer capable of undergoing a retroaldol reaction, thus withdrawing the products from the enzymatic equilibrium.…”

“…In a recent communication [1] we have reported on the enzyme-catalyzed aldol addition of dihydroxyacetone phosphate (DHAP) [in situ generated from fructose 1,6-bisphosphate (FBP)] to various racemic b-hydroxyaldehydes 1 ± 3 bearing a phosphonate group at the x-position (Scheme 1). This reaction, promoted by fructose 1,6-bisphosphate aldolase from rabbit muscle (FruA rab ), allowed the production, in moderate to good yields, of a set of unnatural x-phosphonic deoxysugars 4 ± 6 endowed with potential bioactivity as inhibitors or regulators of metabolic processes.…”

Asymmetrized Tris(hydroxymethyl)methane and Related Synthons: Enantioselective Preparation and Synthetic Applications

“…Once again the MgBr 2 mediated condensation of allylstannanes with BHYMA* gave good results (Table 4). [28] The "induced diastereoselectivity" (ranging from 93:7 to 96:4) was indeed considerably better than the one achieved in the condensation with unsubstituted allylstannanes (Table 2). Scheme 15 Moreover a high degree of "simple diastereoselectivity" (ca.…”

“…[29] As a consequence, a single stereoisomer, among the four possible, could be obtained in 86Ϫ88% diastereoselectivity. Scheme 16 Although we were unable to find conditions for the efficient access to the other three diastereoisomers by direct crotylation of BHYMA*, we developed indirect mehods for obtaining all of them taking advantage of: (a) The chelation controlled reduction [28] of ketones 69, derived by oxidation of the major stereoisomers 65 (Table 5) and (b) the inversion of configuration of the original chiral centre by simple protecting group interchange on the two CH 2 OR arms, taking advantage of the stereochemical properties of these building blocks, in particular of their "diastereodivergency" (see Scheme 16).…”