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16
Aldolases as Catalyst for the Synthesis of Carbohydrates and
Analogs

Pere Clap´ es, Jes´ us Joglar, and Jordi Bujons

16.1
Introduction

The formation of carbon–carbon bonds is one of the cornerstone reactions in
synthetic organic chemistry. Among the methods available, the aldol addition
reaction is a powerful strategy that enables the concomitant functionalization
and creation of stereogenic centers [1]. Aldol addition reaction is a privileged
carboligation procedure to generate polyoxygenated molecules [1a,b] as well as a
straightforward and efficient bottom-up approach for the de novo construction of
carbohydrate-like scaffolds [2]. Among the different methods to accomplish the aldol
addition reaction, the utilization of catalysts (i.e., direct aldol addition) simplifies
the process through a precise activation of the substrates and a stringent control
of the stereochemical course [3]. Hence, developing catalysts for this reaction that
control the stereochemistry at the newly formed C–C bond independently of the
structure of the starting material is of utmost importance.
Among the catalytic methods, the green approach mediated by aldolases is
finding increasing acceptance in chemical research and production of asymmetric
compounds because of the high selectivity and catalytic efficacy and the possibility
to use them in cascade reactions in combination with other enzymes [4]. Aldolases
catalyze reversibly and stereoselectively the aldol addition of a donor component
(i.e., nucleophile), through a ketone enolate or enamine generated at the active
site of the aldolase, onto an acceptor component (i.e., electrophile). Concomitantly,
the stereochemistry at the newly formed stereocenter(s) is, in most cases, strictly
controlled by the enzyme. Moreover, cascade biocatalytic reactions can be designed
by a sequential combination of independent aldol additions catalyzed by different
aldolases in which the aldol product of one reaction becomes the substrate for
the next [5]. During the last two decades, an increasing number of applications of
aldolases in stereoselective synthesis have been reported (for a more comprehensive
coverage of the general topic, we refer the readers to reviews by different authors)
[4d,h, 6].
A particular field of interest for the application of aldolases is in multistep and
cascade reactions for the preparation of carbohydrate-like compounds and analogs

Cascade Biocatalysis: Integrating Stereoselective and Environmentally Friendly Reactions, First Edition.
Edited by Sergio Riva and Wolf-Dieter Fessner.
c 2014 Wiley-VCH Verlag GmbH & Co. KGaA. Published 2014 by Wiley-VCH Verlag GmbH & Co. KGaA.