PUROMYCIN. SYNTHETIC STUDIES. V. 6-Dimethylamino-9-(2'-Acetamino-Β-D-Glucopyranosyl)purine

Abstract

Puromycin has been shown to be a derivative of 6-dimethylamino-9-(3'aminoribosyl)purine (1). In a previous paper (2) a method was described for the glycosidation of 6-dimethylaminopurine on the 9-position via the 2-methylmercapto derivative. Since a search of the literature revealed no example of the glycosidation of a purine with an amino sugar, it would be necessary to solve this problem before a total synthesis of the antibiotic could be effected. The proper blocking group and activation for the coupling of n-glucosamine, as a model amino sugar, with a purine has now been successfully completed.A derivative of n-glucosamine (I) suitable for variation of the N-blocking group is 1,3,4,6-tetraacetyl-2-amino-/3-n-glucopyranose (II) prepared by the elegant method of Bergmann and Zervas (3). This derivative was then N-blocked by acetyl (IV), phthalyl (VI), or carbobenzoxy. The introduction of the phthalyl blocking group by the standard method of direct fusion of the base, II, with phthalic anhydride was unpromising. This difficulty was circumvented by treatment of the base, II, with phthalic anhydride in boiling chloroform which formed the crystalline phthalamic acid, III, in 85 % yield. The ring closure to the phthalimido derivative, VI, did not proceed readily with boiling acetyl chloride. A new and milder method for cyclization of phthalamic acids was devised. Treatment of the phthalamic acid, III, in chloroform with triethylamine and ethyl chlorocarbonate at 0°g ave a mixed anhydride (4) which cyclized at room temperature in 2 hours to the desired phthalimido derivative, VI, in 74-81 % yield.2By proper modification of the literature procedure (5), the conversion of n-glucosamine /3-pentaacetate (IV) to a-bromoaceto-n-glucosamine (Va) was increased from 42 to 55 %. Attempts to condense this bromo sugar derivative with the chloromercury salt of 2-methylmercapto-6-dimethylaminopurine (2) in boiling xylene, toluene, or benzene did not lead to any of the nucleoside derivative (Villa), but decomposition of the bromo sugar took place with consequent formation of the free purine base. Similar results were obtained with the crystalline l-bromo-2-phthalimido-3,4,6-triacetyl-D-glucopyranoside (IXa). Since the bromo phthalylglucosamine, IXa, obviously decomposes at its m.p. of 120°and a-bromoaceto-n-glucosamine (Va) has no definite m.p., but gradually decomposes, the difficulties in the coupling reaction were attributed to the instability

Selenosugars are key and urinary metabolites for selenium excretion within the required to low-toxic range

“…1). 1␣-Chlorogalactosamine tetraacetate (3) (18,19) in Fig. 1 was synthesized from D-galactosamine hydrochloride (1) through the pentaacetate (2) with 47 and 70% yields, respectively, and then reacted with sodium methylselenolate, generated in situ through the reduction of dimethyldiselenide, in acetonitrile at room temperature for 1 h to give the 1␤-methylseleno derivative (4) in a 73% yield as a crystalline material (m.p.…”

Synthesis of an Ursolic Acid Saponin with N‐Acetylglucosamine‐containing Trisaccharide Residue

“…The key trisaccharide donor 13 was prepared as shown in Scheme 1. Starting from 1,3,4,6-tetra-O-acetyl-2-deoxy-2-phthalimido-β-D-glucopyranose (2), 11 compound 3 was obtained as a pure β-anomer (J 1,2 ＝8.8 Hz) by reacting 2 with p-MeO-C 6 H 4 OH under the promotion of BF 3 •Et 2 O in 81.9% yield. After removal of acetyl groups in 3, 6-OH was protected selectively by Tr group 12 and then 3,4-OHs were protected by acetyl groups in situ to produce compound 5 quantitatively.…”

Recent trends in the synthesis of O-glycosides of 2-amino-2-deoxysugars

“…Their preparation, activation, N-deprotection and model glycosidations will be discussed hereafter. 354 Six years later, Akiya and Osawa utilized the latter in glycosylations of simple alcohols and obtained the desired b-glycosides in high yields. 355 Hence in 1976, Lemieux et al proposed the use of 2-phthalimido glycopyranosyl halides for the development of a generally useful preparation of 2-amino-2-deoxy oligosaccharides.…”