Hjm. Gijsen et Ch. Wong, SEQUENTIAL 3-SUBSTRATE AND 4-SUBSTRATE ALDOL REACTIONS CATALYZED BY ALDOLASES, Journal of the American Chemical Society, 117(29), 1995, pp. 7585-7591
This paper describes a useful synthetic strategy based on sequential e
nzyme-catalyzed aldol addition reactions. The aldol reaction of an acc
eptor aldehyde with acetaldehyde, catalyzed by 2-deoxyribose-5-phospha
te aldolase (DERA, EC 4.1.2.4), gives a new aldehyde, which subsequent
ly reacts with a second donor substrate, catalyzed by DERA or another
aldolase. This sequential aldol reaction proceeds because of the forma
tion of a stable cyclic hemiacetal or hemiketal product. In this way s
everal 6-substituted 2,4,6-trideoxyhexoses have been stereoselectively
synthesized via a one-pot double DERA-catalyzed reaction. DERA couple
d with fructose-1,6-diphosphate aldolase from rabbit muscle (RAMA, EC
4.1.2.13) in a one-pot reaction gave a variety of 5-deoxyheptuloses, h
owever not in 100% stereoselectivity. The sequential aldol reactions w
ith four substrates were accomplished by coupling DERA with N-acetylne
uraminic acid aldolase (NeuAc aldolase, EC 4.1.3.3) to give several ni
ne-carbon sialic acid-type sugar derivatives.