Synthesis of porphyrinylamide and observation of N-methylation- induced transecis amide conformational alteration Mio Matsumura a , Aya Tanatani a, * , Tomoyo Kaneko a , Isao Azumaya b , Hyuma Masu c , Daisuke Hashizume d , Hiroyuki Kagechika e , Atsuya Muranaka f, * , Masanobu Uchiyama f, g, * a Department of Chemistry, Faculty of Science, Ochanomizu University, 2-1-1 Otsuka, Bunkyo-ku, Tokyo 112-8610, Japan b Faculty of Pharmaceutical Sciences, Toho University, 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan c Chemical Analysis Center, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522, Japan d Materials Characterization Support Unit, RIKEN Center for Emergent Matter Science (CEMS), Wako-shi, Saitama 351-0198, Japan e Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, 2-3-10 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-0062, Japan f Advanced Elements Chemistry Research Team and Elements Chemistry Laboratory, RIKEN, Wako-shi, Saitama 351-0198, Japan g Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan article info Article history: Received 2 May 2013 Received in revised form 21 October 2013 Accepted 23 October 2013 Available online 29 October 2013 Keywords: Porphyrinylamide Conformation Crystal structure abstract We synthesized porphyrinylamide 4b and its N-methylated derivative 5b. Direct N-methylation of por- phyrinylamides 4 proved unsuccessful, so 5b was obtained via N-methylation of 5-aminoporphyrin 10 with potassium hexamethyldisilazide. The secondary amide 4b exists in trans-amide form, while N- methylated amide 5b exists in the cis-amide form, both in solution and in the crystal. Thus, N-methyl- ation of the amide bond of 4b resulted in trans to cis conformational alteration. Ó 2013 Elsevier Ltd. All rights reserved. 1. Introduction Porphyrin and related chromophores are functional macro- molecules that play important roles in many biological processes, including photosynthetic reaction. 1 In order to develop artificial functional molecules, various porphyrin-related models have been synthesized, including porphyrins covalently linked with porphy- rin 2 (i.e., porphyrin dimers) or other functional aromatic mole- cules. 3 The three-dimensional structures of such molecules have a significant influence on functionality. Therefore, in the synthesis of such supramolecular structures, it is important to control the conformations of the molecular components. We have reported that amide bonds of aromatic secondary amides show strong conformational preference; for example, benzanilide (1) takes the trans-amide form, while N-methyl- benzanilide (2) exists as the cis-amide form in the crystal, 4 and predominantly as the cis-amide form in solution 5 (Fig. 1). The cis conformational preference is also observed with related functional groups (amidine, urea, 4,6 guanidine 7 ). We considered that this conformational property could be utilized to construct interesting three-dimensional aromatic structures, including helical poly- amides, 8 and aromatic multi-layers. 9 Furthermore, some aromatic amide bonds alter their conformations in response to external stimuli, 10 and this phenomenon could be applicable to develop molecular switches or sensors. Here we focused on utilizing the strong conformational preference of amide bonds to construct porphyrin derivatives with unique three-dimensional architecture. Several porphyrin derivatives in which the amide bond is attached directly to the porphyrin ring have been synthesized. 11 However, to Fig. 1. Conformational alteration of benzamide upon N-methylation. * Corresponding authors. Tel./fax: þ81 3 5978 2716 (A.T.); fax: þ81 48 467 2869 (A.M.); fax: þ81 3 5841 0732 (M.U.); e-mail addresses: tanatani.aya@ocha.ac.jp (A. Tanatani), atsuya-muranaka@riken.jp (A. Muranaka), uchiyama@mol.f.u-tokyo. ac.jp (M. Uchiyama). Contents lists available at ScienceDirect Tetrahedron journal homepage: www.elsevier.com/locate/tet 0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.tet.2013.10.069 Tetrahedron 69 (2013) 10927e10932