Rabbit Muscle Aldolase as a Catalyst in Organic Synthesis Article

Bednarski, MD, Simon, ES, Bischofberger, N et al. (1989). Rabbit Muscle Aldolase as a Catalyst in Organic Synthesis . JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 111(2), 627-635. 10.1021/ja00184a034

cited authors

  • Bednarski, MD; Simon, ES; Bischofberger, N; Fessner, WD; Kim, MJ; Lees, W; Saito, T; Waldmann, H; Whitesides, GM

authors

abstract

  • D-Fructose-1,6-bisphosphate aldolase from rabbit muscle (RAMA, EC 4.1.2.13) is a synthetically useful catalyst for the stereoselective aldol condensation between dihydroxyacetone phosphate (DHAP, 1) and aldehydes having a range of structures. This paper demonstrates that more than 50 aldehydes [in addition to its natural substrate, D-glyceraldehyde 3-phosphate, G-3-P (2)] are substrates for RAMA. Unhindered aliphatic, a-heteroatom-substituted, and differentially protected alkoxy and amino aldehydes are substitutes; sterically hindered aliphatic and α,β-unsaturated aldehydes are not. Aromatic aldehydes are either poor as substrates or they do not react. Phosphorylated aldehydes react more rapidly than their unphosphorylated counterparts, and aldehydes substituted in the a position with an electronegative group react more rapidly than unsubstituted aliphatic aldehydes. Permissible variations in the structure of the DHAP moiety are much more restricted; only two—1,3-dihydroxy-2-butanone 3-phosphate (68) and 1,4-dihydroxy-3-butanone-1-phosphonate (69)—of 11 DHAP analogues tested were substrates for RAMA. RAMA is stable under the reaction conditions used in synthetic applications: it withstands organic cosolvents (up to 20% DMSO or EtOH); it can be used in immobilized form, in soluble form, or enclosed within a membrane; it is also air-stable. Syntheses of 5,6-dideoxy-D-threo2-hexulose 1-phosphate (82), 5-0-methyl-D-fructose (85), D-xylulose (88), and peracetylated D-glycero-D-altro-2-octulose (91) on scales of 4 mmol-1 mol demonstrate practical application of this catalytic synthetic methodology. In a limited study of kinetic diastereoselectivity, RAMA exhibits useful selectivity in two cases: with (±)-glyceraldehyde 3-phosphate [2; 20:1 ratio, the major isomer being D-fructose 1,6-bisphosphate (3)] and with (±)-2-(benzyloxy)propanal [19; 3:1 ratio, the major isomer being (S,S,R)-5-(benzyloxy)-3,4-dihydroxy-1-(phosphonooxy)hexan-2-one (91)]. When (±)-3-hydroxybutanal (100) reacts with DHAP, high thermodynamic diastereoselectivity was observed: the ratio of the two stereoisomers (103 to 104) is 97:3 and the major isomer is 5,7-dideoxy-L-gluco-2-heptulopyranose 1-phosphate (103). © 1989, American Chemical Society. All rights reserved.

publication date

  • January 1, 1989

published in

Digital Object Identifier (DOI)

start page

  • 627

end page

  • 635

volume

  • 111

issue

  • 2