Biomimetic Organocatalytic C–C-Bond Formations
53
Our biomimetic C 3 +C n concept allows the synthesis of selectively
and partly orthogonal double protected sugars and amino sugars in one
step. For example l-ribulose (8), d-erythro-pentos-4-ulose (9), 5-deoxyl-ribulose (10), 5-amino-5-deoxy-l-psicose (11), 5-amino-5-deoxy-ltagatose (12) and d-psicose (13) were prepared in this way (Enders and
Grondal 2005; Enders and Grondal 2006). The double acetonide protected d-psicose 13 was quantitatively deprotected with an acidic ionexchange resin (Dowex W50X2-200) to give the parent d-psicose (14,
Scheme 4).
The stereoselective reduction of the ketone function of 9 leads to
a direct entry to selectively protected aldopentoses (‘inversion strategy’)
(Borysenko et al. 1989), which greatly expand the potential of this new
protocol (Scheme 5). Following Evans’ protocol the tetramethylammonium triacetoxyborohydride-mediated reduction provides the syn-diol
15 constituting a protected d-ribose (95%, >96% de). The anti-selective
reduction to 17 was obtained after silyl protection of the free hydroxyl
group of 9 to the OTBS-ether 16 using l-selectride. The aldopentose 18
was then accessible via chemoselective acetal cleavage followed by in
situ cyclization (47% over two steps, >96% de).
Besides reduction, other transformations were performed, for example, reductive amination, nucleophilic 1,2-addtion, deoxygenation or
olefination/reduction and thionation (Enders and Grondal 2006; Grondal 2006).
2.1.2 Direct Organocatalytic Entry to Sphingoids
Sphingoids are long-chain amino-diol and -triol bases that form the
backbone and characteristic structural unit of sphingolipids, which are
important membrane constituents and play vital roles in cell regulation as well as signal transduction (see selected reviews: (Kolter and
Sandhoff 1999; Brodesser et al. 2003; Kolter 2004; Liao et al. 2005)).
Furthermore, glycosphingolipids show important biological activities,
e.g., antitumor, antiviral, antifungal or cytotoxic properties (Naroti et al.
1994; Kamitakahara et al. 1998; Kobayashi et al. 1998; Li et al. 1995).
Phytosphingosines, one of the major classes of sphingoids, have been
isolated and identified either separately or as parts of sphingolipids found
in plants, marine organisms, fungi, yeasts and even mammalian tissues
53
Our biomimetic C 3 +C n concept allows the synthesis of selectively
and partly orthogonal double protected sugars and amino sugars in one
step. For example l-ribulose (8), d-erythro-pentos-4-ulose (9), 5-deoxyl-ribulose (10), 5-amino-5-deoxy-l-psicose (11), 5-amino-5-deoxy-ltagatose (12) and d-psicose (13) were prepared in this way (Enders and
Grondal 2005; Enders and Grondal 2006). The double acetonide protected d-psicose 13 was quantitatively deprotected with an acidic ionexchange resin (Dowex W50X2-200) to give the parent d-psicose (14,
Scheme 4).
The stereoselective reduction of the ketone function of 9 leads to
a direct entry to selectively protected aldopentoses (‘inversion strategy’)
(Borysenko et al. 1989), which greatly expand the potential of this new
protocol (Scheme 5). Following Evans’ protocol the tetramethylammonium triacetoxyborohydride-mediated reduction provides the syn-diol
15 constituting a protected d-ribose (95%, >96% de). The anti-selective
reduction to 17 was obtained after silyl protection of the free hydroxyl
group of 9 to the OTBS-ether 16 using l-selectride. The aldopentose 18
was then accessible via chemoselective acetal cleavage followed by in
situ cyclization (47% over two steps, >96% de).
Besides reduction, other transformations were performed, for example, reductive amination, nucleophilic 1,2-addtion, deoxygenation or
olefination/reduction and thionation (Enders and Grondal 2006; Grondal 2006).
2.1.2 Direct Organocatalytic Entry to Sphingoids
Sphingoids are long-chain amino-diol and -triol bases that form the
backbone and characteristic structural unit of sphingolipids, which are
important membrane constituents and play vital roles in cell regulation as well as signal transduction (see selected reviews: (Kolter and
Sandhoff 1999; Brodesser et al. 2003; Kolter 2004; Liao et al. 2005)).
Furthermore, glycosphingolipids show important biological activities,
e.g., antitumor, antiviral, antifungal or cytotoxic properties (Naroti et al.
1994; Kamitakahara et al. 1998; Kobayashi et al. 1998; Li et al. 1995).
Phytosphingosines, one of the major classes of sphingoids, have been
isolated and identified either separately or as parts of sphingolipids found
in plants, marine organisms, fungi, yeasts and even mammalian tissues