Wiley Acta Medica Okayama 1521-6543 65 4 2013 Synthesis of biopterin and related pterin glycosides 300 309 EN Tadashi Hanaya Department of Chemistry, Faculty of Science, Okayama University Hiroshi Yamamoto School of Pharmacy, Shujitsu University Certain pterins having a hydroxyalkyl side chain at C-6 have been found as glycosidic forms in certain prokaryotes, such as 2′-O-(α-D-glucopyranosyl)biopterin from various kinds of cyanobacteria, and limipterin from a green sulfur photosynthetic bacterium. Synthetic studies on glycosides of biopterin and related pterins have been made in view of the structural proof as well as for closer examination of their biological activities and functions. The syntheses of these natural pterin glycosides have effectively been achieved, mostly through appropriately protected N2-(N,N-dimethylaminomethylene)-3-[2-(4-nitrophenyl)ethyl]pterin derivatives as glycosyl acceptors, and are reviewed here. © 2013 IUBMB Life 65(4):300–309, 2013. No potential conflict of interest relevant to this article was reported.

The Japan Institute of Heterocyclic Chemistry Acta Medica Okayama 0385-5414 70 1 2006 Synthesis of 6- and 7-(1,2,3-Trihydroxy-1,2-O-isopropylidenepropyl)pteridines and Deoxygenation of Their 3’-Hydroxy Groups 355 365 EN Tadashi Hanaya Department of Chemistry, Faculty of Science, Okayama University Daisuke Takayama Department of Chemistry, Faculty of Science, Okayama University Hiroshi Yamamoto Department of Chemistry, Faculty of Science, Okayama University Treatment of 3,4-O-isopropylidene-L-threo-pentos-2-ulose (7) with 5,6-diamino-1,3-dimethyluracil (8) afforded 1,3-dimethyl-6-[(1R,2S)-1,2,3-trihydroxy-1,2-O-isopropylidenepropyl]lumazine (9a) and its 7-substituted isomer (9b). Deoxygenation of 3’-hydroxy groups of 9a,b was investigated in connection with a practical transformation of neopterin into biopterin. No potential conflict of interest relevant to this article was reported.

The Japan Institute of Heterocyclic Chemistry Acta Medica Okayama 0385-5414 85 10 2012 Synthetic Studies on Natural Pterin Glycosides 2375 2390 EN Tadashi Hanaya Department of Chemistry, Faculty of Science, Okayama University Hiroshi Yamamoto School of Pharmacy, Shujitsu University Some pterins having various kind of sugars attached to the hydroxyalkyl side-chain at C-6 are known to occur in certain prokaryotes as exemplified by 2'-O-(α-D-glucopyranosyl)biopterin isolated from various kinds of cyanobacteria. A synthetic exploration of various types of glycosides of biopterin and related pterins has been undertaken owing to a marked interest in their physiological functions and biological activities as well as the structural proof of those natural products. This review summarizes our synthetic studies on natural pterin glycosides by employing the appropriately protected N2-(N,N-dimethylaminomethylene)-3-[2-(4-nitrophenyl)ethyl]pterin derivatives as glycosyl accepters. No potential conflict of interest relevant to this article was reported.

The Japan Institute of Heterocyclic Chemistry Acta Medica Okayama 0385-5414 69 1 2006 Synthesis of Functionalized Phospholane Oxides and Phosphorinane Oxides from 1,4- and 1,5-Di-O-Mesyloxy Compounds 283 294 EN Tadashi Hanaya Department of Chemistry, Faculty of Science, Okayama University Karsten Schürrle Department of Chemistry, Faculty of Science, Okayama University Hiroshi Yamamoto Department of Chemistry, Faculty of Science, Okayama University Treatment of 1,4-di-O-mesyl-2,3-di-O-methyl-L-threitol (8b) with phenylphosphine in the presence of sodium hydride in DMSO, followed by the action of hydrogen peroxide, afforded 3,4-dimethoxy-1-phenylphospholane 1- oxide (7), while the same treatment of 1,5-di-O-mesyl-2,3,4-tri-O-methyl-meso- xylitol (11b) provided 2,3,4-trimethoxy-1-phenylphosphorinane 1-oxide (14). No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0022-152X 62 12 2025 An Improved Synthesis of a Key Intermediate for Glycosylation of Biopterin and Its Application for the First Synthesis of Microcystbiopterin B 2021 2029 EN Tadashi Hanaya Department of Chemistry, Faculty of Science, Okayama University Yuta Maeda Department of Chemistry, Faculty of Science, Okayama University Katsuya Iwasaki Department of Chemistry, Faculty of Science, Okayama University A key intermediate for the selective 2′-O-glycosylation of biopterin, N2-(N,N-dimethylaminomethylene)-1′-O-(4-methoxybenzyl)-3-[2-(4-nitrophenyl)ethyl]biopterin (12), was efficiently synthesized via a novel route starting from d-glucose, leading to an improved overall yield. This new pathway involves the preparation of a 5-deoxy-l-arabinose phenylhydrazone derivative (9) as a crucial intermediate in the construction of the pteridine ring. Utilizing compound 12, the first synthesis of microcystbiopterin B (4) was accomplished by glycosylation of 12 with 4,6-di-O-acetyl-2-O-(4-methoxybenzyl)-3-O-methyl-α-d-glucopyranosyl bromide (19) in the presence of silver triflate and tetramethylurea, followed by stepwise deprotection. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0008-6215 558 2025 First total synthesis of cyanopterin, a pterin glycoside isolated from a cyanobacterium 109710 EN Tadashi Hanaya Department of Chemistry, Faculty of Science, Okayama University Yuta Maeda Department of Chemistry, Faculty of Science, Okayama University Kazumasa Ejiri Department of Chemistry, Faculty of Science, Okayama University The first total synthesis and structural identification of cyanopterin, a pterin glycoside isolated from the cyanobacterium Synechocystis sp. PCC 6803, has been accomplished. The synthesis was achieved by convergent coupling of three key derivatives: d-glucuronate, d-galactose, and 6-hydroxymethylpterin. An α-selective glycosylation enabled efficient construction of the glucuronate–galactose disaccharide, while subsequent β-exclusive glycosylation with the 6-hydroxymethylpterin derivative furnished the desired pterin–disaccharide glycoside. Final deprotection provided cyanopterin in its natural form, allowing confirmation of its precise structure. No potential conflict of interest relevant to this article was reported.

The Japan Institute of Heterocyclic Chemistry Acta Medica Okayama 0385-5414 95 1 2016 Efficient Total Syntheses of Natural Neopterin Glycosides: Neopterin Glucronide and Solfapterin 390 409 EN Tadashi Hanaya Department of Chemistry, Faculty of Science, Okayama University Katsuya Iwasaki Department of Chemistry, Faculty of Science, Okayama University Kaori Saeki Department of Chemistry, Faculty of Science, Okayama University Takafumi Hattori Department of Chemistry, Faculty of Science, Okayama University 1’,2’-Di-O-acetyl-N2-(N,N-dimethylaminomethylene)-3-[2-(4-nitro- phenyl)ethyl]neopterin (11a) and its 1’,2’-di-O-benzoyl analog (11b) were prepared from neopterin in 5 steps, respectively. Glycosylation of 11a with methyl 2,3,4-tri-O-benzoyl-α-D-glucopyranosyluronate bromide (15b) in the presence of silver triflate afforded the corresponding 3’-O-(β-D-gluco- pyranosyl)neopterin derivative (18) in 64% yield. The similar treatment of 11b with 2-azido-3,4,6-tri-O-benzoyl-2-deoxy-α-D-glucopyranosyl bromide (21b) provided the corresponding 3’-O-(α-D-glucopyranosyl)neopterin derivative (23a) in 58% yield. The first syntheses of neopterin glucronide (5) and solfapterin (6) were achieved by successive removal of the protecting groups of 18 and 23a, respectively. No potential conflict of interest relevant to this article was reported.

The Japan Institute of Heterocyclic Chemistry Acta Medica Okayama 03855414 71 3 2007 The First Chemical Synthesis of 6-Thio-D-fructopyranose via Methyl 6-Bromo-6-deoxy-1,3-O-isopropylidene-α-D-fructofuranoside as a Key Intermediate 517 522 EN Tadashi Hanaya Nobuaki Sato Department of Chemistry, Faculty of Science, Okayama University Hiroshi Yamamoto Department of Chemistry, Faculty of Science, Okayama University Selective bromination of sucrose, followed by acetalation with 2,2-dimethoxypropane in 1,4-dioxane in the presence of p-toluenesulfonic acid, afforded methyl 6-bromo-6-deoxy-1,3-O-isopropylidene-α-D-fructofuranoside (4). The first chemical synthesis of 6-thio-D-fructopyranose was accomplished from 4 through its 6-S-acetyl-6-thio derivative. No potential conflict of interest relevant to this article was reported.

The Japan Institute of Heterocyclic Chemistry Acta Medica Okayama 0385-5414 88 2 2014 Selective Preparation of 6- and 7-(Polyhydroxypropyl)pterins from Pentos-2-uloses 1491 1499 EN Tadashi Hanaya Kasumi Ito The Gabriel-Isay condensation of three types of pentos-2-uloses with 2,5,6-triaminopyrimidin-4(3H)-one (3) was examined under both acidic and basic conditions. The condensation of 5-deoxy- and 5-O-protected pentofuranos-2-uloses with 3 at pH 8 afforded 6-substituted pterins as major isomers, whereas the same reaction at pH 3 yielded the 7-substituted pterins predominantly. No potential conflict of interest relevant to this article was reported.

International Society of Pteridinology Acta Medica Okayama 0933-4807 24 1 2013 First Synthesis of Asperopterin A, an Isoxanthopterin Glycoside from Aspergillus Oryzae 3 6 EN Tadashi Hanaya Hiroshi Yamamoto The key precursor, N-2-(N,N -dimethylaminomethylene)-6-hydroxymethyl-8-methyl-3-[2-(4-nitrophenyl)ethyl]-7-xanthopterin (16) was efficiently prepared from 2,5-diamino-6-methylamino-3H-pyrimidin-4-one (5) and ethyl 3-(tert-butyldimethylsilyloxy)-2-oxopropionate (12), followed by the protection of the pteridine ring. Glycosylation of 16 with 1-O-acetyl-2,3,5-tri-O-benzoyl-beta-D-ribofuranose (18) in the presence of tin(IV) chloride yielded the corresponding beta-D-ribofuranoside. Successive removal of the protecting groups of the resulting D-ribofuranoside provided asperopterin A (4b). No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 0385-5414 73 1 2007 Improved syntheses of D-ribo- and 2-deoxy-D-ribofuranose phospho sugars from methyl β-D-ribopyranoside 581 591 EN Tadashi Hanaya Yuko Koga Heizan Kawamoto Hiroshi Yamamoto Methyl 4-deoxy-4-dimethoxyphosphinoyl-2,3-O-isopropylidene-beta-D-ribopyranoside (12a) and methyl 2,4-dideoxy-4-dimethoxyphosphinoyl-beta-D-erythro-pentopyranoside (20) were efficiently prepared respectively from methyl 2,3-O-isopropylidene-beta-D-ribopyranoside (7a) and its 3,4-O-isopropylidene isomer (7b) in appreciably improved total yields compared with those via previously reported routes. Compounds (12a, 20) were led to D-ribofuranose and 2-deoxy-D-ribofuranose phospho sugars (4, 5). No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 0385-5414 72 1 2007 A New Route for Preparation of 2-Deoxy-D-ribofuranose Phospho Sugar 411 420 EN Tadashi Hanaya Hiroyuki Tsukui Naomi Igi Ayashi Noguchi Heizan Kawamoto Hiroshi Yamamoto The addition reaction of dimethyl phosphonate to (2R,4S)-4-(tertbutyldimethylsilyl)oxymethyl-2-methyl-1,3-dioxan-5-one (11a), followed by dehydroxylation, provided 1-O-(tert-butyldimethylsilyl)-3-deoxy-3-dimethoxyphosphinoyl-2,4-O-ethylidene-D-erythritol (13a). Elongation of carbon skeleton of the D-erythrose (14) derived from 13a and then acidic methanolysis gave a mixture of methyl 2,4-dideoxy-4-dimethoxyphosphinoyl-alpha,beta-D-erythropentopyranosides (7), which was led to 2-deoxy-D-ribofuranose phospho sugar (4) in an appreciably improved total yield compared with the procedures via previously reported route. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 0385-5414 86 2 2012 Synthesis of 2-Acetamido-2,5-dideoxy-5-phosphoryl-D-glucopyranose Derivatives: New Phospha-sugar Analogs of N-Acetyl-D-glucosamine 1147 1165 EN Tadashi Hanaya Masahiro Kawaguchi Masakazu Sumi Kazuo Makino Keiko Tsukada Hiroshi Yamamoto Starting with N-acetyl-D-glucosamine, methyl 2-acetamido-3,6-di-O-benzyl-2-deoxy-beta-D-xylo-hexofuranosid-5-ulose (18) was prepared in 7 steps. The addition reaction of dimethyl phosphonate to 18, followed by deoxygenation of its 5-hydroxy group, provided the 5-deoxy-5-dimethoxyphosphoryl-D-glucofuranoside derivative (21a). The hydride reduction of 21a, followed by the action of hydrochloric acid and then hydrogen peroxide, afforded the first D-glucosamine analog (23) having a phosphoryl group in the hemiacetal ring. This was converted into the per-O-acetylated N-acetyl-D-glucosamine phospha-sugar (25), while the same treatment of the 5-deoxy-5-dimethoxyphosphoryl-L-idose dimethyl acetal derivative (13b) afforded the N-acetyl-L-idosamine phospha-sugar (29). No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 1881-0942 84 2 2012 First Synthesis of a Natural Isoxanthopterin Glycoside, Asperopterin-A 801 813 EN Tadashi Hanaya Kazumasa Ejiri Hiroshi Yamamoto The key precursor, N-2-(N,N-dimethylaminomethylene)-6-hydroxymethy1-8-methyl-3[2-(4-nitrophenypethyl]-7-xanthopterin (9) was efficiently prepared from 2,5-diamino-6-methylam1no-3H-pyrimidin-4-one (3) and ethyl 3-(tert-butyldimethylsilyloxy)-2-oxopropionate (11). The first synthesis of asperopterin-A (2b) was achieved by treatment of 9 with 1-O-acetyl-2,3,5-tri-O-benzoy1-beta-D-ribofuranose (15) in the presence of tin(IV) chloride, followed by removal of the protecting groups. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 1881-0942 82 2 2011 An Efficient Synthesis of Antibiotic SF-2312 (3-Dihydroxyphosphoryl-1,5-dihydroxy-2-pyrrolidone) 1675 1683 EN Tadashi Hanaya Chika Itoh N-Benzyloxy-2-(diethoxyphosphoryl)pent-4-enamide (6) was prepared from ethyl diethoxyphosphorylacetate in a 3-step sequence. Oxidative cleavage of the terminal olefin of 6 with osmium tetroxide and sodium periodate afforded 1-benzyloxy-3-diethoxyphosphoryl-5-hydroxy-2-pyrrolidone (7). The first synthesis of racemic SF-2312 was achieved by treatment of 7 with trimethylsilyl bromide, followed by hydrogenolysis. No potential conflict of interest relevant to this article was reported.

International Society of Pteridinology Acta Medica Okayama 0933-4807 19 3 2008 An Efficient Synthesis of 2'-O-(β-D-Ribofuranosyl)biopterin 72 78 EN Tadashi Hanaya Kiyoshi Torigoe Kazuyuki Soranaka Hiroshi Fujita Hiroshi Yamamoto Wolfgang Pfleiderer N(2)-(N,N-Dimethylaminomethylene)-3-[2-(4-nitrophenyl)ethyl]-1',2'-di-O (trimethylsilyl)biopterin (4) was prepared from biopterin (1a, 86% overall yield) in 5 steps. Glycosylation of 4 with 1,2,3,5-tetra-O-acetyl-β D-ribofuranose (5a) and its 2,3,5-tri-O-benzoyl analog (5b) respectively afforded the corresponding 2'-O-(2,3,5-tri-Oacetyl- and 2,3,5-tri-O-benzoyl-β-D ribofuranosyl)biopterin derivatives (6a, 42% and 6b, 60%) as major products. Removal of the protecting groups of 6b provided 2'-O-(β-D-ribofuranosyl)biopterin (1c, 87% overall yield) in 3 steps. No potential conflict of interest relevant to this article was reported.

The Japan Institute of Heterocyclic Chemistry Acta Medica Okayama 1881-0942 76 1 2008 An Efficient Synthetic Route for a Versatile Ciliapterin Derivative and the First Ciliapterin D-Mannoside Synthesis 635 644 EN Tadashi Hanaya Hiroki Baba Mitsunori Kanemoto Hiroshi Yamamoto The key precursor, N(2)-(N,N-dimethylaminomethylene)-1’-O-(4-methoxybenzyl)-3-[2-(4-nitrophenyl)ethyl]ciliapterin (15) was efficiently prepared from D-xylose via an improved route. The first synthesis of 2’-O-(α-D-mannopyranosyl)ciliapterin (2c) was achieved by treatment of 15 with 2,3,4,6-tetra-O-benzoyl-α-D-mannnopyranosyl bromide in the presence of silver triflate and tetramethylurea, followed by removal of the protecting groups. No potential conflict of interest relevant to this article was reported.

Pergamon-Elsevier Science Ltd. Acta Medica Okayama 0040-4020 65 38 2009 Synthetic studies on pterin glycosides: the first synthesis of 2′-O-(α-d-glucopyranosyl)biopterin 7989 7997 EN Tadashi Hanaya Hiroki Baba Hiroki Toyota Hiroshi Yamamoto L-Rhamnose was led, in a 14-step-sequence, to N2-(N,N-dimethylaminomethylene)-1′-O-(4-methoxybenzyl)-3-[2-(4-nitrophenyl)ethyl]biopterin (23), an appropriately protected precursor for 2′-O-glycosylation, while 4,6-di-O-acetyl-2,3-di-O-(4-methoxybenzyl)-α-d-glucopyranosyl bromide (32), a novel glycosyl donor, was efficiently prepared from d-glucose in 8 steps. The first synthesis of 2′-O-(α-d-glucopyranosyl)biopterin (2a) was achieved by treatment of the key intermediate 23 with 32 in the presence of silver triflate and tetramethylurea, followed by successive removal of the protecting groups. No potential conflict of interest relevant to this article was reported.

International Society of Pteridinology Acta Medica Okayama 0933-4807 20 Special Issue 2009 First Synthesis of a Representative, Natural Pterin Glycoside: 2’-O-(α-D-Glucopyranosyl)biopterin 36 41 EN Tadashi Hanaya Hiroshi Yamamoto Wolfgang Pfleiderer Glycosylation of N(2)-(N,N-dimethylaminomethylene)-1’-O-(4-methoxybenzyl)-3-[2-(4-nitrophenyl) ethyl]biopterin (14) with the novel donor 4,6-di-O-acetyl-2,3-di-O-(4-methoxybenzyl)-α-D-glucopyranosyl bromide (19) in the presence of silver triflate and tetramethylurea predominantly afforded the corresponding α-D-glucopyranoside (20a), from which 2’-O-(α-D-glucopyranosyl)biopterin (1) was obtained by the successive removal of the protecting groups. No potential conflict of interest relevant to this article was reported.

International Society of Pteridinology Acta Medica Okayama 0933-4807 21 3 2010 First Synthesis of a Natural Neopterin Glycoside: 3'-O-(β-D-Glucopyranosyluronic acid)neopterin 79 83 EN Tadashi Hanaya Takafumi Hattori Daisuke Takayama Hiroshi Yamamoto 1',2'-Di-O-acetyl-N2-(N,N-dimethylaminomethylene)-3-[2-(4-nitrophenyl)ethyl]neopterin (1) was prepared from neopterin in 5 steps. Glycosylation of 1 with methyl 2,3,4-tri-O-benzoyl-α-D-glucopyranosyluronate bromide in the presence of silver triflate and tetramethylurea afforded the corresponding 3'-O-(methyl β-D-glucopyranosyluronate) neopterin derivative (2) in 64% yield. The first synthesis of 3'-O-(β-D-glucopyranosyluronic acid)neopterin was achieved by successive removal (4 steps) of the protecting groups of 2. No potential conflict of interest relevant to this article was reported.

The Japan Institute of Heterocyclic Chemistry Acta Medica Okayama 1881-0942 80 2 2010 Synthesis of 6-Hydroxymethylpterin α- and β-D-Glucosides 1013 1025 EN Tadashi Hanaya Hiroki Baba Kazumasa Ejiri Hiroshi Yamamoto The key precursor, N(2)-(N,N-dimethylaminomethylene)-6-hydroxymethyl-3-[2-(4-nitrophenyl)ethyl]pterin (11) was efficiently prepared from 2,5,6-triamino-4-hydroxypyrimidine (8) in 5 steps. The first, unequivocal synthesis of 6-hydroxymethylpterin α-D-glucoside (6a) was achieved by treatment of 11 with 4,6-di-O-acetyl-2,3-di-O-(4-methoxybenzyl)-α-D-glucopyranosyl bromide (16) in the presence of tetraethylammonium bromide and N-ethyldiisopropylamine, followed by removal of the protecting groups, while 6-hydroxymethylpterin β-D-glucoside (6b) was prepared by means of selective glycosylation of 11 with 2,3,4,6-tetra-O-benzoyl-α-D-glucopyranosyl bromide (12) in the presence of silver triflate and tetramethylurea. No potential conflict of interest relevant to this article was reported.

The Japan Institute of Heterocyclic Chemistry Acta Medica Okayama 1881-0942 77 2 2009 First Synthesis of Biopterin α-D-Glucoside 747 753 EN Tadashi Hanaya Hiroki Baba Hiroshi Yamamoto A novel glycosyl donor, 4,6-di-O-acetyl-2,3-di-O-(4-methoxy-benzyl)-α-D-glucopyranosy bromide (15) was efficiently prepared from D-glucose in 8 steps. The first synthesis of 2’-O-(α-D-glucopyranosyl)biopterin (2) was achieved by treatment of the key precursor, N(2)-(N,N-dimethylamino- methylene)-1’-O-(4-methoxybenzyl)-3-[2-(4-nitrophenyl)ethyl]biopterin (6) with 15 in the presence of silver triflate and tetramethylurea, followed by removal of the protecting groups. No potential conflict of interest relevant to this article was reported.

Pergamon-Elsevier Science Ltd. Acta Medica Okayama 0040-4020 64 9 2008 Efficient total syntheses of natural pterin glycosides: limipterin and tepidopterin 2090 2100 EN Tadashi Hanaya Hiroki Baba Hiroki Toyota Hiroshi Yamamoto The key, versatile precursors N-2-(N,N-dimethylaminomethylene)-1'-O-(4-methoxybenzyl)-3-[2-(4-nitrophenyl)ethyl]biopterin (29a) and its ciliapterin analog (29b) were prepared, respectively, from D-xylose (in 14 steps) and L-xylose (in 11 steps). Treatment of 29a and 29b with 3,4,6-tri-O-acetyl-2-deoxy-2-phthalimido-beta-D-glucopyranosyl bromide in the presence of silver triflate and tetramethylurea, followed by removal of the protecting groups, led to the first selective syntheses of limipterin (3) and tepidopterin (5), respectively. No potential conflict of interest relevant to this article was reported.

The Japan Institute of Heterocyclic Chemistry Acta Medica Okayama 1881-0942 74 1 2007 An Efficient, One-Pot Synthesis of Fosfomycin Dialkyl Esters from (R)-2-Tosyloxypropanal 983 989 EN Tadashi Hanaya Yuichi Nakamura Hiroshi Yamamoto (R)-2-Tosyloxypropanal (4) was prepared from D-mannitol in a 7-step sequence (51% overall yield). Addition of dialkyl phosphonates to 4 in the presence of titanium isopropoxide and the subsequent treatment with DBU stereoselectively afforded, in one-pot, fosfomycin dimethyl (5a) and dibenzyl (5b) esters both in 58% isolated yield. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 1990 Synthetic Studies of Sugar Analogs Having a Phosphorus Atom in the Hemiacetal Ring EN No potential conflict of interest relevant to this article was reported.