Synthesis of stereospecifically face-protected chlorophyll derivatives Shin-ichi Sasaki, Hiroshi Takebe, Tadashi Mizoguchi and Hitoshi Tamiaki * Department of Bioscience and Biotechnology, Faculty of Science and Engineering, Ritsumeikan University, Kusatsu, Shiga 525-8577, Japan Received 9 August 2005; accepted 8 September 2005 Available online 23 September 2005 Abstract—A pair of zinc chlorins having a bridged moiety between the 3 and 13 2 -positions on the front or back side of its p-face were synthesized, and their asymmetric coordination ability towards pyridine was determined in benzene. Ó 2005 Elsevier Ltd. All rights reserved. Chlorophylls (Chls) are known to play important roles as main pigment molecules in the initial stage of photo- synthesis. 1 In the crystal structures of pigment–protein complexes reported so far, 2 Chls are found to be fixed in proper locations by the fifth coordination of a protein residue (or others including water) to their central mag- nesium. 3 To investigate the coordination chemistry of Chls, we have recently developed zinc chlorins having a bridged moiety between 3- (or 8-) and 17-positions, which would restrict axial ligation to one side of the two macrocycle p-faces. 4 Since the linkage of the syn- thetic compounds was situated only above its front side, 5 an alternative route has been required to synthe- size any strapped structure covering the back p-face. Here we report the synthesis of a pair of zinc chlorins having a bridge between the 3- and 13 2 -positions on the front or back-face of chlorin macrocycle. Two kinds of strapped zinc chlorins Zn-1/2 and their acyclic reference compounds Zn-3/4 were synthesized as shown in Scheme 1. Chlorin 5 possessing the 3-hydroxymethyl group was used as a starting material, 6 which was prepared by modifying a Chl-a/a 0 mixture extracted and derived from the cyanobacterium, Spirulina geitleri. Esterification of the 3 1 -hydroxy group with 5-hexenoic acid using EDCÆHCl and DMAP, 7 and the following transesterification of the 13 2 -methoxycarbonyl group with 8-nonen-1-ol by CMPI and DMAP in reflux- ing toluene 8,9 gave 6 having two vinyl groups at the terminals of the 3- and 13 2 -substituents in 73% yield. To form a strapped bridge, ring-closing metathesis of 6 was performed using Cl 2 (PCy) 2 Ru@CHPh as a cata- lyst 10 to give 7 in 77% yield. 11 Because the intramolecu- lar cyclization formed an alkene linkage as its cis/trans mixture, the bridge of chlorin 7 was hydrogenated in the presence of PtO 2 to transform a dodecamethylene unit for simplicity. During these synthetic procedures, the ratio of 13 2 S-(a 0 ) and R-epimers (a) was retained constant at ca. 1:6. The free-base mixture 13 2 S-1 and 13 2 R-2 was separated by reversed-phase HPLC, 12 and zinc was inserted 13 to give desired Zn-1/2. 14 On the other hand, esterification of the 3 1 -hydroxy group of 5 with acetic acid gave a mixture of 3 and 4, which was zinc-metallated and separated by HPLC to give refer- ence compounds Zn-3/4. Figure 1a shows the absorption spectra of Zn-1 and Zn-2 in THF. The Q y peak maximum (651.4 nm) of Zn-1 (solid line) is slightly red-shifted compared to that (650.8 nm) of Zn-2 (dotted line) by 0.6 nm (14 cm À1 ). A similar difference between each diastereomer was also observed for free-base chlorins 1 and 2. Because the small differences were almost the same as those in their reference compounds (Zn-)3/4, the bridging dodeca- methylene unit of (Zn-)1/2 caused a little strain on the chlorin macrocycle. The characteristics of the observed CD spectra of Zn-1/2 in Figure 1b were quite similar to those of Zn-3/4 or naturally occurring Chl-a 0 /a (see SI), indicating that the strapped compounds Zn-1/2 still retain the structural and spectral characteristics of Chl- a 0 /a, and the bridging moiety is expected to just cover a p-face for single axial ligation. Their molecular model- ling study by PM3/MM+ calculation 15 also supported the proposed structures of (Zn-)1/2 in which the 0040-4039/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved. doi:10.1016/j.tetlet.2005.09.034 Keywords: Chlorin; Coordination; Macrocycles; Metathesis; Photo- synthesis. * Corresponding author. Tel.: +81 77 566 1111; fax: +81 77 561 2659; e-mail: tamiaki@se.ritsumei.ac.jp Tetrahedron Letters 46 (2005) 7687–7689 Tetrahedron Letters