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

Angelina Georgieva; Manabu Hirai; Yuichi Hashimoto; Tadashi Nakata; Yasushi Ohizumi; Kazuo Nagasawa

doi:10.1055/s-2003-40195

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Synthesis 2003(9): 1427-1432
DOI: 10.1055/s-2003-40195

SPECIALTOPIC

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

Angelina Georgieva^c, Manabu Hirai^b, Yuichi Hashimoto^a, Tadashi Nakata^c, Yasushi Ohizumi^b, 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

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