Synthesis of Glycoconjugated Phthalonitriles for New Phthalocyanine-Based Photosensitizers

Abstract

Excellent photophysical and photochemical properties completed by magnificent takeup rates in malignant tissues attracted a great deal of interest to the application of glycosylated and glycoconjugated phthalocyanines in photodynamic therapy. In this study we describe the concise synthesis and full characterization of 16 differently 3,6-bisglycoconjugated phthalonitriles 3, 5, 6, 8, and 48-59, which are precursors for a new generation of photosensitizers, namely, nonperipheral glycoconjugated phthalocyanines. The first example for the synthesis of a nonperipheral glycoconjugated zinc phthalocyanine 60 from phthalonitrile 48 is also presented in this work.

Glycosylated Metal Phthalocyanines

“…4,5-Diglycosylated phthalonitriles, in which two galactose units connected via carbon-6, were also synthesized using the same method [30,33,34,35]. Several attempts for the connection of a carbohydrate residue in the positions 3 and 6 of phthalonitrile were published by Hanack, Ziegler et al recently (Scheme 3) [36].…”

Glycosylated Metal Phthalocyanines

“…Using this procedure the octaglycosylated phthalocyanines 23a-i were obtained then in yields between 55% and 78% and deprotected to form the PcZns 24a-i [32,34,35]. 24a-i gave high triplet quantum yields ranging from 0.68 to 0.88 [39].…”

“…4,5-Diglycosylated phthalonitriles, in which two galactose units connected via carbon-6, were also synthesized using the same method [30,[33][34][35]. Several attempts for the connection of a Scheme 1.…”

“…4,5-Diglycosylated phthalonitriles, in which two galactose units connected via carbon-6, were also synthesized using the same method [30,[33][34][35]. Several attempts for the connection of a 4,5-Diglycosylated phthalonitriles e.g., 10 were prepared for the first time by Hanack, Ziegler, and coworkers (Scheme 2) [32] from 4,5-difluorophthalonitrile (9b) and anomerically-deprotected sugars, using K 2 CO 3 as base.…”

“…Molecules 2015, 20, page-page 7 After several attempts using a variety of conditions 10a was heated in DMF with 30 mol % hexamethyldisilazane (HMDS), p-toluenesulfonic acid and Zn(OAc) at 125-130 °C overnight [34,35]. Using this procedure the octaglycosylated phthalocyanines 23a-i were obtained then in yields between 55% and 78% and deprotected to form the PcZns 24a-i [32,34,35].…”