Facile enzymatic synthesis of ketoses
Over the past decades, 11 rare ketopentoses and ketohexoses have been successfully synthesized by scientist. However, all the reported processes suffer from complicated purification steps, low yield, or expensive starting materials. Studies of rare ketoses have been hampered by the lack of efficient preparation methods.
At this point, a convenient, efficient and cost-effective platform undergoing “phosphorylation®de-phosphorylation” cascade reaction for the facile synthesis of ketoses is described by which all non-readily available ketopentoses and ketohexoses were prepared from common and inexpensive starting materials with high yield and purity without having to undergo a tedious isomer separation step.
In the first reaction step of Scheme 1, we combined thermodynamically unfavorable bioconversions of common (3S)-sugars to the desired (3S)-ketoses (route A) or (3R)-ketoses (route B) with phosphorylation reactions by substrate-specific kinases (Fructokinase (HK) from humans in route A, L-rhamnulose kinase (RhaB) from Thermotoga maritima MSB8 in route B). In the second reaction step, phosphate adenosines (ATP and ADP) were selectively removed by a convenient method called silver nitrate precipitation. Then, acid phosphatase (AphA) was added to hydrolyze the phosphate groups to produce the desired ketoses. Notably, both reaction steps can be performed in a one-pot fashion. Scheme 2 was designed to prepare L-fructose from DL-glycerol 3-phosphate and glycerol relying on the aldol condensation reaction using rhamnulose bisphosphate aldolase (RhaD). L-psicose was further prepared from L-fructose using the targeted phosphorylation strategy shown in Scheme 3.
Facile Enzymatic Synthesis of Ketoses.
Wen L, Huang K, Wei M, Meisner J, Liu Y, Garner K, Zang L, Wang X, Li X, Fang J, Zhang H, Wang PG
Angew Chem Int Ed Engl. 2015 Oct 19