Novel Preparation of a 2′-O-Acetyl-1′-O-(4-methoxybenzyl)-l-biopterin Derivative, a Versatile Precursor for a Selective Synthesis of l-Biopterin Glycosides

Abstract

P r e p a r a t i o n o f a 2 ¢ -O -A c e t y l -1 ¢ -O -( 4 -m e t h o x y b e n z y l ) -L -b i o p t e r i n D e r i v a t i v e Abstract: L-Rhamnose was converted, over a 13-step-sequence, into 2¢-O-acetyl-N 2 -(N,N-dimethylaminomethylene)-1¢-O-(4-methoxybenzyl)-3-[2-(4-nitrophenyl)ethyl]-L-biopterin, an appropriately protected precursor of 1¢-O-and 2¢-O-monoglycosyl-L-biopterin.Thus, the first selective synthesis of these L-biopterin glycosides was accomplished by treatment of the precursor with either DDQ or sodium methoxide, then with tetra-O-benzoyl-a-D-glucopyranosyl bromide in the presence of silver triflate and tetramethylurea, followed by removal of the remaining protecting groups.

Synthesis of biopterin and related pterin glycosides

“…A marked improvement has been made to establish an efficient synthetic protocol to achieve completely regioselective 2′‐ O ‐glycosylation using a suitably 1′‐ O ‐protected (with p ‐methoxybenzyl (PMB)) biopterin derivative ( 10 ) as a key glycosyl acceptor (35, 36) (Scheme a). From a retrosynthetic analysis outlined in Scheme a compound 10 was thought best to be prepared by the condensation of 2,5,6‐triamino‐4‐hydroxypyrimidine ( 11 ) with 3‐ O ‐protected L ‐ erythro ‐pentos‐2‐ulose ( 12 ), which in turn would be derived from D ‐xylose via 3‐ O ‐protected 5‐deoxy‐ L ‐arabinose 13 involving C‐4 inversion and then C‐5 deoxygenation.…”

“…An efficient glycosylation is shown in Scheme for the condensation of 10 with tetra‐ O ‐benzoyl‐α‐ D ‐glucopyranosyl bromide ( 8 ) in the presence of silver triflate and tetramethylurea (TMU) in dichloromethane, affording the 2′‐ O ‐β‐ D ‐glucopyranosyl derivative 18 as sole product in 75% yield. Removal of the protecting groups of 18 was carried out by the successive treatment with 2,3‐dichloro‐5,6‐dicyano‐ p ‐benzoquinone (DDQ) (to cleave the PMB group), sodium methoxide (to cleave the benzoyl groups), aqueous ammonia (to cleave the N , N ‐dimethylaminomethylene group), and 1,8‐diazabicyclo[5.4.0]undec‐7‐ene (DBU) (to cleave the NPE group) to give 2′‐ O ‐(β‐ D ‐glucopyranosyl)biopterin ( 1e ), the anomeric isomer of natural pterin glycoside 1b (34, 35).…”

First Synthesis of Biopterin α-D-Glucoside

“…In a previous paper, 14 we developed an efficient synthetic protocol for the pterin 2'-O-glycosides by way of the key intermediate, In the present study, we therefore have undertaken to prepare an efficient glycosyl donor leading the preponderant production of pterin α-glycosides. We now describe the first synthesis of the representative, natural pterin glycoside, 2'-O-(α-D-glucopyranosyl)biopterin (2).…”

“…Hydrolysis of 12 in 70% acetic acid afforded methyl 2,3-di-O-PMB-1-thio-β-D-glucopyranoside (13), which was then treated with acetic anhydride and pyridine to give the desired 4,6-di-O-acetyl derivative (14). While glycosylation of 6 with 4.0 mol equiv.…”

First Synthesis of a Natural Neopterin Glycoside: 3'-O-(β-D-Glucopyranosyluronic acid)neopterin

“…By contrast, the functional roles of pterin glycosides have remaind obscure, though some inhibitory activities against tyrosinase were reported for biopterin D-glucoside (2) (23). Despite a considerable interest from the viewpoint of their biological activities and functions as well as the structural proof of hitherto reported natural products, attempts at preparation of natural pterin glycosides have so far scarcely been made, except for our synthetic studies on biopterin and ciliapterin glycosides (24)(25)(26)(27)(28)(29)(30)(31). We describe herein an efficient synthesis of 3'-O-(β-D-glucopyranosyluronic acid)neopterin (6) as the first synthetic example of a natural neopterin glycoside.…”