Manfred Gerken

Darstellung Von β-D-Olivosyl(1→3)-D-olivosiden Aus Mithramycin

Abstract The benzyl glycoside 4 obtained from 2-bromo-2-deoxy-α-0-quinovosyl bromide 1, readily accessible by the dibromomethyl methyl ether reaction of 2, is deformylated to give the monohydroxy compound 5 which is used in glycosidation reactions. Treatment of 3 with dibromomethyl methyl ether results in the formation of the labile β-furanosyl bromide 7 and the cyrstalline pyranosyl bromide 8 in a ratio of 1:2, both of which are further characterized by their methyl glycosides 10 and 11, respectively. Action of dibromomethyl methyl ether at room temperature on the benzyl ether 6, conventionally prepared from 3, is shown to proceed initially to the glycosyl bromide 9. Compound 9 is cleaved to the 4-formyl-blocked pyranosyl bromide 12, and only after prolonged reaction time gives the pyranosyl halide 8. The glycosidation of the glycosyl bromide 1 with benzyl-4–0-benzyl-α-D-olivoside 13 in the presence of silver carbonate and silicate is a sluggish reaction and gives rather low yields of the β-and the α, l-...

Neue synthesen von aureolsäuretrisacchariden

Abstract The silver trifluoromethylsulfonate-promoted condensation of 4- O -benzoyl-2-bromo-2,6-dideoxy-3- O -formyl-α- d -glucopyranosyl bromide ( 4 ) and ebnzyl 4- O -benzoyl-2-bromo-2,6-dideoxy-β- d -glucopyranoside ( 5 ) yielded a disaccharide which, after ester cleavage, gave a 3′,4′-diol component ( 13 ). By N -iodosuccinimide-mediated condensation of d -mycaral monoacetate with ( 13 ), benzyl O -(4- O -acetyl-2,6-dideoxy-2-iodo-3- C -methyl-α- d altropyranosyl-(1→3)- O -2,6-dideoxy-β- d - arabino -hexopyranosyl- (1→3)-4- O -benzoyl-2,6-dideoxy-β- d - arabino -hexopyranoside ( 14 ) was obtained with complete regio- and stereo-specificity [only α- d -(1″→3′)-linkage] but moderate yield; it may be transformed into an isomer of the E-D-C-trisaccharide of mithramycin. In contrast to the α-series, the methyl-branching of benzyl 4- O -benzoyl-2,6-dideoxy-β- d - erythro -hexopyranosid-3-ulose gave the 3- C -methyl- d - arabino - and - d - ribo -glycosides with only little stereoselectivity. The glycosylation of benzyl 4- O -benzoyl-3- O -(4- O -benzoyl-2-bromo-2,6-dideoxy-β- d -glucopyranosyl)-2-bromo-2,6-dideoxy-β- d - glucopyranoside ( 14 ), selectively unprotected at the 3′ position, with 4 gave in excellent yield and stereoselectivity (β:α 10:1) preponderantly an all β- d -inked derivative. Following selective ester cleavage, reductive dehalogenation, and oxidation, the trisaccharide glycosid-ulose )( 24 ) was obtained. The methyl-branching with methyl lithium occurred stereospecifically and generated exclusively a terminal 3- C -methyl- d - arabino -hexopyranoside unit, thus yielding another E-D-C-trisaccharide of the aureolic acids, namely, benzyl O -(2,6-dideoxy-3- C -methyl-β- d - arabino -hexopyranosyl)-(1→3)- O -(2,6-dideoxy-β- d - arabino -hexopyranosyl)-(1→3)-2,6- dideoxy-β- d - arabino -hexopyranoside.

Semisynthetic β-Rhodomycins: A New Approach to the Synthesis of 4-O-Methyl-β-Rhodomycins

ABSTRACT Syntheses of 4-O-methyl-β-rhodomycins are described. Glycosylation (trimethylsilyl triflate, dichloromethane-acetone 10:1, -30 °C) of 4-O-methyl-10-O-p-nitrobenzoyl-β-rhodomycinone, obtained from β-rhodomycinone (βRMN) in a 6-step synthesis, with 1-O-tert-butyl(dimethyl)silylated derivatives of 4-O-acetyl- or 4-O-p-nitrobenzoyl-2,3,6-tri-deoxy-3-trifluoroacetylamino-β-L-arabino- and lyxo-hexopyranoses or 2,6-di-O-acetyl-2,6-dideoxy-β-L-lyxo-hexopyranose afforded 7-O-α-L-glycosyl-β-rhodomycinones. Removal of the O- and N-acyl groups with 0.1M and 1M NaOH gave the 7-O-(3-amino-2,3,6-trideoxy-α-L-arabino- and lyxo-hexopyranosyl)-4-O-methyl-β-rhodomycinones and 7-O-(2,6-dideoxy-α-L-lyxo-hexopyranosyl)-4-O-methyl-β-rhodomycinone.

Semisynthetic ∊-Isorhodomycins: Glycosylation and Modification Reactions1

Abstract The syntheses of 7-O-α-L-daunosaminyl-∊-isorhodomycinone (6) and 7-O-α-L-rhodosaminyl-∊-isorhodomycinone (7) are described. The glycosyl donors 1,4-di-O-p-nitrobenzoyl-3-N-trifluoroacetyl-α,β-L-daunosamine and 1,4-di-O-acetyl-α,β-L-rhodosamine have proven to be the most suitable for the glycosylation of ∊-isorhodomycinone (∊-iso RMN) (3), using the TMS triflate method. Deblocking (0.5 N NaOH) of the protected glycoside 4 led to the desired 7-O-glycosyl-∊-isorhodomycinones 5 and 6. The daunosaminyl glycoside 6 was methylated (CH2O, NaCNBH3) to provide the rhodosaminyl derivative 7. The photolytic demethylation of this product selectively provided the 7-O-(3′-N-methyl-α-L-daunosaminyl)-∊-isorhodomycinone (8).

Synthesis of 2′-Iodo Analogues of β-Rhodomycins1

Abstract 10-O-(R/S)Tetrahydropyranosyl-β-rhodomycinone (5a,b) was prepared via 7,9-O-phenylboronyl-β-rhodomycinone (3) from β-rhodomycinone (1). Glycosidation of 5a,b with 3,4-di-O-acetyl-1,5-anhydro-2,6-dideoxy-L-arabino-hex-1-enitol (3,4-di-O-acetyl-L-rhamnal) (6) and 3,4-di-O-acetyl-1,5-anhydro-2,6-dideoxy-L-lyxo-hex-1-enitol (3,4-di-O-acetyl-L-fucal) (7) using N-iodosuccinimide gave the corresponding 7-O-glycosyl-β-rhodomycinones 8a,b, 9a,b and 10a,b, 11a,b. After cleavage of the THP-ether and O-deacetylation 7-O-(2,6-dideoxy-2-iodo-α-L-manno-hexopyranosyl)-β-rhodomycinone (14) and 7-O-(2,6-dideoxy-2-iodo-α-L-talo-hexopyranosyl)-β-rhodomycinone (16) were obtained.

Semisynthetic 4-O-Methyl-ß-Rhodomycins: Synthesis and Structure-Activity Relationships

ABSTRACT The synthesis of 7-O-α-L-daunosaminyl-4-O-methyl-β-rhodomycinone (3) and the determination of its cytotoxic potency compared to that of the natural 7-O-α-L-dau-nosaminyl-β-rhodomycinone (4) are described. Starting with natural β-rhodomycinone (7), trimethylsilyl protecting groups were attached to the hydroxy groups at position 7 and 10, and the 4-OH group was subsequently methylated (MeI/Cs2CO3), thus providing the 4-O-methyl-7, 10-bis-O-trimethylsilyl-β-rhodomycinone (10). The two TMS groups were then deblocked to give 4-O-methyl-β-rhodomycinone (12). In a 3-stage synthesis 12 was converted into 4-O-methyl-10-O-trifiuoroacetyl-s-rhodomycinone (15) to which l, 4-bis-O-p-nitrobenzoyl-3-N-trifluoroacetyl-L-daunosamine 16 was selectively linked to afford the 7-O-α-glycoside 17. The acyl protective groups are removed by treatment with 1N NaOH to give 3.

Synthesis and Structure Elucidation of p-Methoxybenzoyl Derivatives of Rhodomycins1

Abstract It was determined that β-rhodomycin-II (rhodomycin A) (1), β-rhodomycin-I (rhodomycin B, betaclamycin T) (2) and γ-rhodomycin-I (iremycin) (3) may regioselectively be acylated at OH-4′ of the sugar (rhodosamine) moiety(ies), using a two-phase (chloroform/water) solvent system and sodium bicarbonate as a base. This report exemplarily describes the synthesis of the corresponding p-methoxybenzoate esters of 1, 2, and 3, i. e. derivatives 4–7, and highlights the structure elucidation of isomers 5a and 5b.

Photolytic N-Mono-Demethylation of Rhodosaminylanthracyclinone Type Anthracyclines1

ABSTRACT It was found that rhodosaminylanthraclinone-type anthracyclines are readily N-mono-demethylated upon irradiation with visible light, leading to 3′-N-methyl-α-L-daunosarninylanthracyclinones in good yields. The reaction is preferentially observed with rhodosaminylanthracyclinones in which OH-4′ of the sugar (rhodosamine) moiety is not further glycosylated. 3′-N-methyl-α-L-daunosaminyl anthracyclinones provide key compounds that can readily be further derivatized.