Design and synthesis of photosensitizer,13,15-cycloimides chlorin p6

LIU Minghui; LIU Junhong; HAN Guiyan; ZHANG Xingjie; SHENG Chunquan; YAO Jianzhong

doi:10.3969/j.issn.1006-0111.2017.01.007

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Objective To design and prepare 13,15-cycloimides chlorin p6 ( 1 ),a class of chlorin related antitumor photosensitizers,which contain a more stable six-membered cyclic imide comparing to the exocyclic anhydride ring of purpurin-18 ( 2 ). Compounds ( 1 ) exhibit strong absorption at long wavelengths near λ_max 700 nm to take full advantage of greater tissue penetration. Methods Pheophorbide a ( 3 ) was obtained by acid hydrolysis of chlorophylla,which was from crude chlorophyll extracts of Chinese traditional herb named Silkworm excrement. Purpurin-18 ( 2 ) was prepared by air oxidation and alkali open loop simultaneously on five-membered beta-keto carboxylic ester ring of pheophorbide a ( 3 ). Finally,the target compounds 1a ~ 1j were synthesized via condensation of its anhydride ring with various amines including carboxyl-protected amino acids. Results Target compounds 1a ~ 1j were successfully synthesized in yields ranged from 32.6% to 65.2%. Their structures were confirmed by elemental analysis,ESI-MS and ¹H NMR spectra. Conclusion Treatment of purpurin-18 ( 2 ) with amines can produce target compounds 1a ~ 1j . The starting raw material was inexpensive and readily available. The reaction conditions were mild and workup was convinient.

Design and synthesis of photosensitizer,13,15-cycloimides chlorin p6

1. School of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China

2. School of Pharmacy, Second Military Medical University, Shanghai 200433, China

3. School of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China;School of Pharmacy, Second Military Medical University, Shanghai 200433, China

Received Date: 2016-11-16

Rev Recd Date: 2016-12-12

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Abstract: Objective To design and prepare 13,15-cycloimides chlorin p6 ( 1 ),a class of chlorin related antitumor photosensitizers,which contain a more stable six-membered cyclic imide comparing to the exocyclic anhydride ring of purpurin-18 ( 2 ). Compounds ( 1 ) exhibit strong absorption at long wavelengths near λ_max 700 nm to take full advantage of greater tissue penetration. Methods Pheophorbide a ( 3 ) was obtained by acid hydrolysis of chlorophylla,which was from crude chlorophyll extracts of Chinese traditional herb named Silkworm excrement. Purpurin-18 ( 2 ) was prepared by air oxidation and alkali open loop simultaneously on five-membered beta-keto carboxylic ester ring of pheophorbide a ( 3 ). Finally,the target compounds 1a ~ 1j were synthesized via condensation of its anhydride ring with various amines including carboxyl-protected amino acids. Results Target compounds 1a ~ 1j were successfully synthesized in yields ranged from 32.6% to 65.2%. Their structures were confirmed by elemental analysis,ESI-MS and ¹H NMR spectra. Conclusion Treatment of purpurin-18 ( 2 ) with amines can produce target compounds 1a ~ 1j . The starting raw material was inexpensive and readily available. The reaction conditions were mild and workup was convinient.

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Design and synthesis of photosensitizer,13,15-cycloimides chlorin p6

doi: 10.3969/j.issn.1006-0111.2017.01.007

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