Premium
Borate as a Phosphate Ester Mimic in Aldolase‐Catalyzed Reactions: Practical Synthesis of L ‐Fructose and L ‐Iminocyclitols
Author(s) -
Sugiyama Masakazu,
Hong Zhangyong,
Whalen Lisa J.,
Greenberg William A.,
Wong ChiHuey
Publication year - 2006
Publication title -
advanced synthesis and catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.541
H-Index - 155
eISSN - 1615-4169
pISSN - 1615-4150
DOI - 10.1002/adsc.200600356
Subject(s) - dhap , aldolase a , dihydroxyacetone phosphate , chemistry , dihydroxyacetone , substrate (aquarium) , fructose , fructose bisphosphate aldolase , aldolase b , yield (engineering) , glyceraldehyde , phosphate , biochemistry , enzyme , organic chemistry , stereochemistry , glycerol , dehydrogenase , oceanography , materials science , metallurgy , geology
Abstract Dihydroxyacetone phosphate (DHAP)‐dependent aldolases have been widely used for the organic synthesis of unnatural sugars or derivatives. The practicality of using DHAP‐dependent aldolases is limited by their strict substrate specificity and the high cost and instability of DHAP. Here we report that the DHAP‐dependent aldolase L ‐rhamnulose 1‐phosphate aldolase (RhaD) accepts dihydroxyacetone (DHA) as a donor substrate in the presence of borate buffer, presumably by reversible in situ formation of DHA borate ester. The reaction appears to be irreversible, with the products thermodynamically trapped as borate complexes. We have applied this discovery to develop a practical one‐step synthesis of the non‐caloric sweetener L ‐fructose. L ‐Fructose was synthesized from racemic glyceraldehyde and DHA in the presence of RhaD and borate in 92 % yield on a gram scale. We also synthesized a series of L ‐iminocyclitols, which are potential glycosidase inhibitors, in only two steps.