Total syntheses of sterically locked phycocyanobilin derivatives with a 15Z-anti or a 15E-anti CD-ring component were performed toward elucidation of the stereochemistry and function of the chromophore in phytochromes. In the course of the construction of a sterically locked 15E-anti CD-ring component employing 5-tosylpyrrolin-2-one derivatives as the D-ring, the Ts group was found to be rearranged under acidic conditions to give a mixture of regioisomers, both of which could be transformed into the same CD-ring precursor via detosylation with a base followed by Wittig-like coupling reaction. In addition, a sterically locked 15E-anti biliverdin derivative was also synthesized.Phytochromes, one of the best-characterized photoreceptors in plants, are a widespread family of red/far-red light responsive photoreceptors first discovered in plants 1 and have been recently also discovered in bacteria, 2 fungi, 3 and slime molds. 4 They play critical roles in various light-regulated processes, ranging from phototaxis and pigmentation in bacteria to seed germination, chloroplast development, shade avoidance, and flowering in higher plants. All phytochromes have a covalently attached linear tetrapyrrole (bilin) chromophore that absorbs light in the red and far-red region.5 Three different bilins are used as chromophores: land plants use phytochromobilin (P¯B), 6 and cyanobacteria use phycocyanobilin (PCB), 7 which is also a chromophore of the light-harvesting pigment, phycocyanin, and differs from P¯B only by substitution of the vinyl group at the C18 position with an ethyl group. 6,7b,8 The P¯B and PCB chromophores bind covalently to the apoprotein by a thioether bond through the A-ring ethylidene side chain. Some bacterial phytochromes carry biliverdin (BV) as a natural chromophore (Figure 1). 3,9 We found that the BV covalently binds to the apoprotein of Agrobacterium phytochrome Agp1 via its A-ring vinyl side chain, 10 which was recently confirmed by X-ray crystallographic analysis of other bacteriophytochromes.
11The interchange between the physiologically inactive red light absorbing Pr-form and the active far-red light absorbing Pfr-form is the most essential for the light absorbing and biological processes in the phytochrome chromophore function (Figure 1). It is commonly accepted that the first step in the photoconversion from Pr to Pfr is a Z to E isomerization around the C15=C16 double bond between the C-and D-rings of the bilin chromophores.
12In order to analyze the structure and function of the chromophores in the reconstituted phytochromes, we have synthesized P¯B, PCB, the modified PCBs, and BVs, in free acid forms by developing efficient methods for the preparation of each pyrrole ring, a new coupling reaction between them, and palladium-catalyzed deprotection of allyl propanoate side chains of the B-and C-rings under mild conditions.13 Furthermore, we have succeeded for the first time in synthesizing the sterically locked 15Z-syn, 15Z-anti, 15E-syn, and 15E-anti BV derivatives, 14,15 which made it possib...