344
2
General Synthetic Methods
Abbreviations
DBU
1,8-diazabicyclo[5.4.0]undec-7-ene
DMSO dimethyl sulfoxide
DMF dimethylformamide
HCMV human cytomegalovirus
NHDF normal human fibroblasts
PTC
phase transfer catalysis
RCM ring-closing metathesis
TIBAL tri-iso-butyl aluminum
1 Introduction
Sugar derivatives containing a double bond are an important class of compounds often used
in stereocontrolled synthesis of optically pure targets. Their chemistry: preparation, reactions,
and application in targeted synthesis is well developed and described in a number of monographs [1,2,3,4,5]. Therefore the classical methods, which have been introduced to the synthetic chemistry of sugars since (at least) the 1950s and are still very useful for their preparation
will be presented in this report, which is an update of an earlier report [6]. The general methodology presented here will refer to the previous report rather than to original literature, but will
be illustrated by more recent examples.
Only occasionally are unsaturated sugar derivatives such as blasticidin A (1), which inhibits
blast disease in rice, found in nature. However, the non-natural unsaturated sugars often possess potent biological activity. The most representative example is, undoubtedly, 2, 3 -dideoxy2, 3 -didehydro-thymidine d4T (Stavudine, Cerit ® )—approved as the fourth anti-HIV drug
by the US Food and Drug Administration—which exhibits an effect comparable to AZT in
HIV-infected CEM cells (in vivo), is less toxic than AZT (the first drug used in an antiHIV treatment) for bone marrow stem cells and was found to be less inhibitory to mitochondrial DNA replication [6,7]. Another example, neuraminic acid derivative 2, is the antisialyl-inhibitory anti-influenza drug [1]. It is also known that the L-nucleosides are important
components of antiviral agents; for example, L-2 3 -dideoxy-2 3 -didehydro-5-fluorocytydine
(L-Fd4C) exhibits potent anti-HBV (antihepatitis B virus) activity ( > Fig. 1) [8,9].
Generally two main classes of unsaturated sugars in which (1) the anomeric carbon atom is
involved in a double bond (glycals) and (2) the unsaturation is placed between other carbon
atoms are known. One has to discuss also derivatives with the exo- and endo-unsaturated bonds
(either olefins/dienes or acetylenes). Another class of unsaturated monosaccharides is represented by the open-chain sugars with the double bond(s) and/or triple bond present in the
molecule. The examples of different types of unsaturated sugars are shown in > Fig. 2.
Compounds such as glycals will not be discussed here, unless they are used as substrates for
the preparation of other, non-anomeric, unsaturated derivatives.
Unsaturated sugar chirons are versatile starting materials in organic synthesis. Many complex natural products whose structure incorporates five- and six-membered carbocyclic rings
2
General Synthetic Methods
Abbreviations
DBU
1,8-diazabicyclo[5.4.0]undec-7-ene
DMSO dimethyl sulfoxide
DMF dimethylformamide
HCMV human cytomegalovirus
NHDF normal human fibroblasts
PTC
phase transfer catalysis
RCM ring-closing metathesis
TIBAL tri-iso-butyl aluminum
1 Introduction
Sugar derivatives containing a double bond are an important class of compounds often used
in stereocontrolled synthesis of optically pure targets. Their chemistry: preparation, reactions,
and application in targeted synthesis is well developed and described in a number of monographs [1,2,3,4,5]. Therefore the classical methods, which have been introduced to the synthetic chemistry of sugars since (at least) the 1950s and are still very useful for their preparation
will be presented in this report, which is an update of an earlier report [6]. The general methodology presented here will refer to the previous report rather than to original literature, but will
be illustrated by more recent examples.
Only occasionally are unsaturated sugar derivatives such as blasticidin A (1), which inhibits
blast disease in rice, found in nature. However, the non-natural unsaturated sugars often possess potent biological activity. The most representative example is, undoubtedly, 2, 3 -dideoxy2, 3 -didehydro-thymidine d4T (Stavudine, Cerit ® )—approved as the fourth anti-HIV drug
by the US Food and Drug Administration—which exhibits an effect comparable to AZT in
HIV-infected CEM cells (in vivo), is less toxic than AZT (the first drug used in an antiHIV treatment) for bone marrow stem cells and was found to be less inhibitory to mitochondrial DNA replication [6,7]. Another example, neuraminic acid derivative 2, is the antisialyl-inhibitory anti-influenza drug [1]. It is also known that the L-nucleosides are important
components of antiviral agents; for example, L-2 3 -dideoxy-2 3 -didehydro-5-fluorocytydine
(L-Fd4C) exhibits potent anti-HBV (antihepatitis B virus) activity ( > Fig. 1) [8,9].
Generally two main classes of unsaturated sugars in which (1) the anomeric carbon atom is
involved in a double bond (glycals) and (2) the unsaturation is placed between other carbon
atoms are known. One has to discuss also derivatives with the exo- and endo-unsaturated bonds
(either olefins/dienes or acetylenes). Another class of unsaturated monosaccharides is represented by the open-chain sugars with the double bond(s) and/or triple bond present in the
molecule. The examples of different types of unsaturated sugars are shown in > Fig. 2.
Compounds such as glycals will not be discussed here, unless they are used as substrates for
the preparation of other, non-anomeric, unsaturated derivatives.
Unsaturated sugar chirons are versatile starting materials in organic synthesis. Many complex natural products whose structure incorporates five- and six-membered carbocyclic rings