First Synthesis of a Natural Pterin Glycoside: Microcystbiopterin B

PS2 Poster session 2 Even numbers
Location (hall): 
Start/end time: 
Tuesday, July 2, 2019 - 15:45 to 17:15

Tadashi Hanaya1, Yuta Maeda1, Katsuya Iwasaki1

1Faculty of Science, Okayama University, Okayama, Japan

Some pteridines having various kind of sugars attached to the hydroxyalkyl side-chain at C-6 are known to occur in certain prokaryotes. As for a glycoside of biopterin (1), 2'-O-(α-D-glucopyranosyl)biopterin (2) was isolated from various kinds of cyanobacteria [1]. We have undertaken a synthetic exploration of various types of natural pterin glycosides owing to a marked interest in their physiological functions and biological activities as well as the structural proof of those natural products [2]. We present here the first sythesis of microcystbiopterin B (3), which was isolated from Microcystis spp. bloom biomass [3] (Scheme 1).

The key, versatile precursor N²-(N,N-dimethylaminomethylene)-1’-O-PMB-3-NPE-biopterin (8) was efficiently prepared from the D-xylofuranose derivative (4) via 5–7 in 11 steps involving condensation of the phenylhydrazone (6) with 2,4,5-triamino-6-hydroxypyrimidine. Meanwhile, the glycosyl donor 2-O-PMB-3-O-methyl-α-D-glucopyranosyl bromide (9) was prepared from D-glucose in 11 steps. Glycosylation of 8 with 9 in the presence of silver triflate and tetramethylurea predominantly afforded the corresponding α-D-glucopyranoside (10). The first synthesis of microcystbiopterin B (3) was achieved by successive removal of the protecting groups of 10. 

Scheme 1. Synthesis of microcystbiopterin B (3).

  1. a) Forrest, H. S.; van Baalen, C.; Myers, J. Arch. Biochem. Biophys. 1958, 78, 95–99. (b) Matsunaga, T.; Burgess, J. G.; Yamada, N.; Komatsu, K.; Yoshida, S.; Wachi, Y. Appl. Microbiol. Biotechnol. 1993, 39, 250–253. (c) Choi, Y. K.; Hwang, Y. K.; Kang, Y. H.; Park, Y. S. Pteridines 2001, 12, 121–125.
  2. Hanaya, T.; Yamamoto, H. IUBMB Life 2013, 65, 300–309.
  3. Lifshits, M.; Kovalerchik, D.; Carmeli, S. Phytochemistry 2016, 123, 69–74.