Biomimetic Organocatalytic C–C-Bond Formations
59
2.1.3 Direct Organocatalytic Entry to Carbasugars
Carbasugars (Sollogoub and Sinay 2006; Suami and Ogawa 1990), also
known as pseudosugars (McCasland et al. 1966), are characterized by
the replacement of the ring oxygen of monosaccharides by a methylene group (for reviews see: Suami 1987; Suami 1990; Ogawa 1988)
(Fig. 4). Not only saturated carbasugars are known, but also unsaturated
ones bearing a ring double bond. Interestingly, they are often recognized
by enzymes instead of the original sugar. Because of the lack of the acetal moiety, such carbasugars are stable towards hydrolysis (Berecibar
et al. 1999). Furthermore, they often show interesting biological properties, for instance, they are glycosidase inhibitors, antibiotics, antivirals
or plant growing inhibitors (Musser 1992; Witczak 1997; Dwek 1996).
Typical examples of naturally occurring carbasugars are streptol (Isogai
et al. 1987), valienamine (Horii et al. 1971), validamine (Kameda and
Horii 1972; Kameda et al. 1984), cyclophellitol (Atsumi et al. 1990a,b),
(+)-MK7607 (Yoshikawa et al. 1994) or the family of gabosines (Bach
et al. 1993). (+)-MK7607 has effective herbicidal activity and is the
4-epimer of streptol, a plant-growth inhibitor. They are two representative examples of eight possible diastereomers of the class of the unsaturated 5a-carbasugars characterized by an exocyclic hydroxymethyl
moiety (Fig. 4).
Altogether, four diastereomers are already known, three of them are
naturally occurring and the fourth one has been synthesized in racemic
form. Most interestingly, all of these compounds are bioactive, but unfortunately direct and flexible approaches to synthesize different stereoisomers or derivatives have not yet been reported. (For 5a-carbasugar
syntheses, see: Ogawa and Tsunoda 1992; Chupak et al. 1998; Lubineau and Billault 1998; Rassu et al. 2000; Mehta and Lakshminath
2000; Song et al. 2001; Holstein Wagner and Lundt 2001; Ishikawa
et al. 2003). We therefore developed a modular strategy for the synthesis
of carbasugars, which was demonstrated by an efficient and straightforward synthesis of 1-epi-(+)-MK7607 (31) (Grondal and Enders 2006).
The retrosynthetic analysis for 31 is depicted in Scheme 9 and involves
the construction of the cyclohexene core via a ring-closing metathesis.
The second disconnection is a (R)-proline-catalyzed aldol reaction be-
59
2.1.3 Direct Organocatalytic Entry to Carbasugars
Carbasugars (Sollogoub and Sinay 2006; Suami and Ogawa 1990), also
known as pseudosugars (McCasland et al. 1966), are characterized by
the replacement of the ring oxygen of monosaccharides by a methylene group (for reviews see: Suami 1987; Suami 1990; Ogawa 1988)
(Fig. 4). Not only saturated carbasugars are known, but also unsaturated
ones bearing a ring double bond. Interestingly, they are often recognized
by enzymes instead of the original sugar. Because of the lack of the acetal moiety, such carbasugars are stable towards hydrolysis (Berecibar
et al. 1999). Furthermore, they often show interesting biological properties, for instance, they are glycosidase inhibitors, antibiotics, antivirals
or plant growing inhibitors (Musser 1992; Witczak 1997; Dwek 1996).
Typical examples of naturally occurring carbasugars are streptol (Isogai
et al. 1987), valienamine (Horii et al. 1971), validamine (Kameda and
Horii 1972; Kameda et al. 1984), cyclophellitol (Atsumi et al. 1990a,b),
(+)-MK7607 (Yoshikawa et al. 1994) or the family of gabosines (Bach
et al. 1993). (+)-MK7607 has effective herbicidal activity and is the
4-epimer of streptol, a plant-growth inhibitor. They are two representative examples of eight possible diastereomers of the class of the unsaturated 5a-carbasugars characterized by an exocyclic hydroxymethyl
moiety (Fig. 4).
Altogether, four diastereomers are already known, three of them are
naturally occurring and the fourth one has been synthesized in racemic
form. Most interestingly, all of these compounds are bioactive, but unfortunately direct and flexible approaches to synthesize different stereoisomers or derivatives have not yet been reported. (For 5a-carbasugar
syntheses, see: Ogawa and Tsunoda 1992; Chupak et al. 1998; Lubineau and Billault 1998; Rassu et al. 2000; Mehta and Lakshminath
2000; Song et al. 2001; Holstein Wagner and Lundt 2001; Ishikawa
et al. 2003). We therefore developed a modular strategy for the synthesis
of carbasugars, which was demonstrated by an efficient and straightforward synthesis of 1-epi-(+)-MK7607 (31) (Grondal and Enders 2006).
The retrosynthetic analysis for 31 is depicted in Scheme 9 and involves
the construction of the cyclohexene core via a ring-closing metathesis.
The second disconnection is a (R)-proline-catalyzed aldol reaction be-