An Efficient Synthesis of Antibiotic SF-2312 (3-Dihydroxyphosphoryl-1,5-dihydroxy-2-pyrrolidone)

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

First Synthesis of Asperopterin A, an Isoxanthopterin Glycoside from Aspergillus Oryzae

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)

First Synthesis of a Representative, Natural Pterin Glycoside: 2’-O-(α-D-Glucopyranosyl)biopterin

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

An Efficient, One-Pot Synthesis of Fosfomycin Dialkyl Esters from (R)-2-Tosyloxypropanal

(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

First Synthesis of a Natural Isoxanthopterin Glycoside, Asperopterin-A

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

First Synthesis of Biopterin α-D-Glucoside

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

Synthetic studies on pterin glycosides: the first synthesis of 2′-O-(α-d-glucopyranosyl)biopterin

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

Improved syntheses of D-ribo- and 2-deoxy-D-ribofuranose phospho sugars from methyl β-D-ribopyranoside

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)

Efficient total syntheses of natural pterin glycosides: limipterin and tepidopterin

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

Synthesis of 6-Hydroxymethylpterin α- and β-D-Glucosides

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