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Synthesis of (-)-Deoxoprosophylline, (þ)-2-epi-
Deoxoprosopinine, and (2R,3R)- and (2R,3S)-3-
Hydroxypipecolic Acids from D-Glycals
Hari Prasad Kokatla, Rima Lahiri, Pavan K. Kancharla,
Venkata Ramana Doddi, and Yashwant D. Vankar*
Department of Chemistry, Indian Institute of Technology
Kanpur 208 016, India
Received March 18, 2010
FIGURE 1. Structures of prosophyllines and related molecules.
1-3 and Cassia4 alkaloid 4 (Figure 1) are medicinally
important as they possess anesthetic, analgesic, and antibio-
tic activities.5 (-)-Deoxoprosophylline (1), (-)-prosophyl-
line, and (þ)-2-epi-deoxoprosopinine (3), having interesting
structural features of 2,6-cis-disubstituted piperidin-3-ol,
were isolated from the leaves of Prosopis africana Taub.3
These contain a hydrophobic aliphatic tail and a hydrophilic
headgroup and thus could be assumed to resemble the cyclic
structure of safingol (6) and sphingosine (7).6 While the polar
headgroup is essential for glycosidase inhibition,7 the ali-
phatic long chain facilitates lipid membrane penetration.
These distinctive properties enhance the therapeutic poten-
tial of these compounds for the treatment of diseases such as
diabetes, viral infection, and cancer. Due to these promising
biological activities and structural features, many newer
approaches toward the synthesis of these molecules have
been developed. There are several reports in literature for the
synthesis of these molecules starting from chiral building
blocks such as amino acids,8 carbohydrates,9 vitamin C,10
and malic acid.11 However, either some of these building
blocks are expensive or the syntheses may require many
steps. Thus, for example, synthesis of (þ)-deoxoprosophyl-
line from D-glycals was achieved in 15-16 steps.9a-c Further,
only one report is available for the synthesis of the target
New syntheses of (-)-deoxoprosophylline, (þ)-2-epi-
deoxoprosopinine, and (2R,3R)- and (2R,3S)-3-hydroxy-
pipecolic acids are reported. Utilization of the chiral
functionalities of Perlin aldehydes, derived from 3,4,6-
tri-O-benzyl glycals, has been done along with chemo-
selective saturation of olefins and reductive aminations as
key steps.
A number of naturally occurring piperidine alkaloids and
their derivatives exhibit important biological properties.
In addition, a number of other N-heterocyclic compounds
have also been found to be useful as pharmaceuticals and
agrochemicals.1 In particular, hydroxylated pyrrolidine, pi-
peridine, pyrrolizidine, and indolizidine alkaloids and their
derivatives have received extensive attention due to their
well-established action as glycosidase inhibitors.2 Among
piperidine alkaloids, Prosopis africana alkaloids3 such as
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Stoltefuss, J. In Handbook of Experimental Pharmacology; Kuhlmann, J., Puls,
W., Eds.; Springer: Berlin, 1996; Vol. 119, p 411. (c) Winchester, B.; Fleet, G. W. J.
Glycobiology 1992, 2, 199.
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4608 J. Org. Chem. 2010, 75, 4608–4611
Published on Web 06/04/2010
DOI: 10.1021/jo100489k
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2010 American Chemical Society