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Synthesis 2003(9): 1427-1432
DOI: 10.1055/s-2003-40195
SPECIALTOPIC
© Georg Thieme Verlag Stuttgart ˙ New York

Stereoselective Synthesis of Novel Ptilomycalin A Analogs via Successive 1,3-Dipolar Cycloaddition Reactions and their Ca2+-ATPase Inhibitory Activity

Angelina Georgievac, Manabu Hiraib, Yuichi Hashimotoa, Tadashi Nakatac, Yasushi Ohizumib, Kazuo Nagasawa*a
a Institute of Molecular and Cellular Biosciences, The University of Tokyo, Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan
e-Mail: nagasawa@iam.u-tokyo.ac.jp;
b Department of Pharmaceutical Molecular Biology, Faculty of Pharmaceutical Sciences, Tohoku University, Aoba, Aramaki, Aoba-ku, Sendai 980-8578, Japan
c Institute of Physical and Chemical Research (RIKEN), Wako, Saitama 351-0198, Japan
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Publication History

Received 5 May 2003
Publication Date:
24 June 2003 (online)

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Abstract

The pentacyclic guanidine compounds 4 and 5 were stereoselectively­ synthesized as novel ptilomycalin A and crambescidin analogs. The synthetic method involves successive 1,3-dipolar cycloaddition reactions which effectively access the key intermediates, trans- and cis-2,5-disubstituted pyrrolidine 8 having hydroxyl groups at the β-positions on their side chains. Among the analogs synthesized, 4b and 5b exhibited significant inhibitory activity against Ca2+-ATPase.

Key Words

ptilomycalin A - 1,3-dipolar cycloaddition - nitrone - pentacyclic guanidine - Ca2+-ATPase inhibitory activity