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

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-α-d-glucopyranosyl bromide in the presence of silver triflate and tetramethylurea, followed by removal of the remaining protecting groups.

Key words

l-biopterin glycosides - limipterin - glycosylations - ­pteridine - protecting groups

References and Notes

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16

When acidic hydrolysis of methyl 2,3-O-isopropylidene-4-O-PMB-α-l-rhamnopyranoside was attempted to obtain 4-O-PMB-l-rhamnose(8), removal of the PMB group preferentially took place rather than hydrolysis of methyl glycoside. Therefore we employed 1-propenyl glycoside, which is cleavable under weaker acidic conditions.

19

A similar condensation of non-protected 5-deoxy-l-erythro-pentos-2-ulose with the same pyrimidine derivative has been reported to provide an 8:2 mixture of 6- and 7-substituted pterins in a relatively low yield (37%; ref. 18).

20

Selected NMR data for 14a: ¹H (600 MHz, CDCl₃): δ = 1.23 (3 H, d, J _{2 ′,3 ′} = 6.6 Hz, H-3′), 4.77 (1 H, d, J _{1 ′,2 ′} = 4.4 Hz, H-1′), 5.36 (1 H, qd, H-2′), 8.96 (1 H, s, H-7). ¹³C (151 MHz, CDCl₃): δ = 15.92 (C-3′), 71.76 (C-2′), 82.21 (C-1′), 128.36 (C-4a), 149.88 (C-7), 150.71 (C-6), 153.63 (C-8a), 157.55 (C-2), 161.83 (C-4).
Selected NMR data for 14b: ¹H (600 MHz, CDCl₃): δ = 1.22 (3 H, d, J _{2 ′,3 ′} = 6.6 Hz, H-3′), 4.66 (1 H, d, J _{1 ′,2 ′} = 4.2 Hz, H-1′), 5.37 (1 H, qd, H-2′), 8.78 (1 H, s, H-6). ¹³C (151 MHz, CDCl₃): δ = 15.61 (C-3′), 71.94 (C-2′), 82.26 (C-1′), 129.29 (C-4a), 159.98 (C-7), 140.92 (C-6), 153.17 (C-8a), 157.88 (C-2), 161.83 (C-4).

22

Use of SnCl₄ as an activator resulted in the formation of diol 4 by cleavage of PMB group instead of glycosylation.

24

General Procedure for Glycosylation of 15.
To a solution of 15 (56 mg, 0.10 mmol), glycosyl bromide (0.30 mmol) and TMU (0.012 mL, 0.10 mmol) in dry CH₂Cl₂ (1.0 mL) was added silver triflate (56 mg, 0.22 mmol). The mixture was stirred at r.t. for 3 h, diluted with CHCl₃, and filtered through Celite^®. The filtrate was washed with aq NaHCO₃, dried (MgSO₄), and evaporated in vacuo. The residue was purified by column chromatography to give the 2′-O-glucopyranosyl-l-biopterin derivative.