Abst6ct : p-Fructosc-1,6-b isphosphate a ldo lase f rom rabbi musc le (RA tA, EC 4.1.2 l3) is a synthet ica l ly uscfu lcata lys for the stcreoselective aldolcbndensation between dihydroxyacetone phosphate (DHAP, l) and aldehl 'des having a rangc of structurcs. This paper dcmonstratcs that more than 50 aldehydcs [in addition to its natural substratc, >glyccraldehyde 3-phcPFtc' G-3-P (2) l arc iu6st ra tes for RAMA. Unhindered a l iphat ic , a-heteroarom-subst r tu ted, an d i f ie rent ia l ly protectcd.a lkory and amino aldehydes are substi tutes;sterical ly hindercd al iphatic and a,6-unsaturated aldehydes are not. Aromatic aldehydcs are either poot t substrates or they do not react. Phosphorylated aldehydcs react more rapidly than thcir unphosphorylated counterparts, and aldehydes substi tuted in the a posit ion with an electroncgative group react more rapidl l ' than unsubsti tutcd al iphatic aldehydes. Pcrmissible variat ions in ie structure of the DHAP moiety' are much more restr icted; only two-I,3' d ihydroxy-2-butanone 3-phosphate (68) and 1,4-d ihydroxy-3-butanonel -phosphonate (69)-o f I I DHAP analogues tcs tcd weic substrates for RA\{A. neVn is stable under tire reattion conditions used in synthetic applications: it withstands organic cosolvents (up to 207o D\1SO or EIOH); i can be uscd in immobil ized iorm, in soluble form, or enclosed within a mcmbranc; i is a lso a i r -s tab le . Synthcscs of 5 ,6-d ideoxy-Dthreo-2-hexulose l -phosphate (82) ,5-O-methy l -Df ructose (85) , o-xy lu lcc (8t), and peracetylatedvglycero-o-altru2-octulose (91) on scales of 4 mmol-l moldemonstrate practical appl icat iongf thit catalyt ic synthetic methodoiogy. In a l imited srudy of kinetic diastereoselectivi ty, RAMA exhibits useiul select ivi ty in tyo cascsl * i i r (*)-glyccraldchydc 3-phosphate [2; 20: ' l rat io, the major isomer being >fructose 1,6-bisphosphate (3)] andwilh (+)-2-(benzyloxyipropanal [19; 3:t rai io, i r i major isomer being (S,S,R)-5-(benzyloxy)-3,4-dihydroxy' l-(phosphon*xl) ' h.*n-i-on. igtlj 'When 1+j-f -hydroxybuunal (lm) reacs with DHRP, high thermodynamic diasterecelectivity was sbccnrcd: the ratio of the two stcrcoisomers (ror to lo{) is 97:3 and the major isomer is 5,?-didcoxy-t-gluco2-heptulopyrance l'phcpbatc (103) .