Untersuchungen zur Darstellung von Desoxyzucker‐Steroidglycosiden

Abstract

In stereoselektiven Reaktionen lassen sich die Glycale 1, 2 und 8 mit Cholesterin sowie Digitoxigenin nach dem N-Iodsuccinimid-Verfahren zu den 2-Desoxy-2-iod-a-glycosiden 3, 4 , s und 9 kondensieren. Bei den langsamen Umsetzungen treten die direkten N-Iodsuccinimidaddukte wie z.B. 6 als Nebenprodukte auf. In Butanon reagiert 11 nur teilweise zu den erwarteten Glycosiden 12 bzw. 13, bevorzugt bilden sich die Hex-2-enopyranoside 17 bzw. Studies on the Synthesis of Stereoid Glycosides of Deoxy Sugars')The 2-deoxy-2-iodo-a-glycosides 3, 4, 5, and 9 are obtained stereoselectively by condensation of cholesterin and digitoxigenin with the glycals 1, 2, and 8 in the presence of Niodosuccinimidc. In a concommitant side reaction thc formation of the direct N-iodosuccinimide adducts like e. g. 6 is observed. Similar trcatmcnt of 11 in butanone only partially leads to the expected glycosides 12 or 13 but rather to the formation of the hex-2-enopyranosides 17 or 18. The latter can also be obtained by a Ferrier rearrangement and their structures are assured by spectroscopy and by hydrogenation (to 20). Following hydrogenolytic deiodination the cardenolide glycosides 10, 14, and 15 are obtained. Acid-catalyzed glycosylation of triacetyldigitoxose 21 with digitoxigenin yields the a-and 0-anomers 10 and 25 in a maximum yield of 50% and a ratio of approximately 2: 3. At elevated temperatures the relative amount of the 0-component 25 incrcascs with, however, heavily decreasing yields. Glycosylation of acetobromodigitoxose 22 using various silver salt promoters similarly gives approximately 50% yield and a ratio of a: 0 = 2: 3.Herzglycoside zahlen in Europa nach wie vor zu dcn haufigst eingesetzten Therapeutica in Fallen von Herzinsufizienz. Abgesehen von gewissen chemischen Modifikationen erfolgt die Isolierung nahezu ausschliel3lich aus pflanzlichcn Extrakten. Die cardiotonische Wirkung geht vom Aglycon aus, wahrend der Saccharidanteil die pharmakokinetischen Eigenschaften wie Resorption und Abklingquote steuert *I. Den erwiinschten positiv inotropen sowie negativ chronotropen Effekten der Herzglycosidc stehen als Nachteil unter anderem ihre recht 0 VCH Verlagsgesellschaft mbH, D-6940 Weinheim, 1985

Methods for 2-Deoxyglycoside Synthesis

“…For example, silver silicate was developed by Paulsen and co-workers for β-selective couplings. 55 , 56 While Thiem and co-workers found that this catalyst was not effective in their studies on the synthesis of digitoxin, 57 Binkley and co-workers found that it was useful for the construction of β-linked olivose sugars commonly found in the anthracycline antitumor antibiotics. 58 , 59 Interestingly, selectivity in these couplings appeared to be dependent on the acceptor.…”

“…Heterogeneous silver catalysts can offer advantages in these reactions in terms of both product purification and selectivity of the glycosylation reaction. For example, silver silicate was developed by Paulsen and co-workers for β-selective couplings. , While Thiem and co-workers found that this catalyst was not effective in their studies on the synthesis of digitoxin, Binkley and co-workers found that it was useful for the construction of β-linked olivose sugars commonly found in the anthracycline antitumor antibiotics. , Interestingly, selectivity in these couplings appeared to be dependent on the acceptor. With a 4-tosyl-protected acceptor 25a , the glycosylation with an olivose bromide donor 24 produced disaccharide 26a in 84% yield with good selectivity (1:11 α:β).…”

Special Problems in Glycosylation Reactions: 2‐Deoxy Sugars

“…This leads to glycosyl succinimides which can adopt predominantly an inverted ' C d (D) chair conformation [30]. To this respect, nucleophilicity of the alcohol can be increased by a previous 0-tributylstannylation which allows better reactivity in NIS-promoted addition to glycals (excellent results are thus obtained with the axially configurated 4-hydroxy group of various L-fucose derivatives) [ 3 11.…”

Stereoselective synthesis of triterpene and steroid 2-deoxy-α-glycosides using iodonium dicollidine perchlorate

“…3 The same promoters were successfully used for the synthesis of steroid 2-deoxy-a-glycosides and oligosaccharides. 4,5 In a continuation of our studies we extended a number of biologically active triterpenes and steroid alcohols used and carried out giycosylation of methyl esters of 18a-(la), II-deoxo-(lb), and 18,19-dehydroglycyrrhetic acids (le) with di-O-acetyl-u-rhamnal (2) and acetylcholic acid methyl ester (ld) with tri-O-acetyI-t~-glucal (3) in the presence of IDCP.…”