Mina A. Nashed

O-benzylated oxazoline derivatives of 2-acetamido-2-deoxy-d-glucopyranose from 1-propenyl glycosides. synthesis of the propenyl glycosides and their direct cyclization

Abstract 1-Propenyl 2-acetamido-3,4,6-tri- O -acetyl-2-deoxy-α- and β- d -glucopyranosides ( 3α , 3β ) were obtained by the successive isomerization and acetylation of the known allyl glycosides 1α and 1β . The allyl glycosides were also converted, via their benzylidene 4,6-acetals, into the 4,6-di- O -benzyl-3- O -(2-butenyl) derivatives 9α and 9β . The simultaneous decrotylation and isomerization of 9β , followed by acetylation, gave 1-propenyl 2-acetamido-3- O -acetyl-4,6-di- O -benzyl-2-deoxy-β- d -glucopyranoside ( 11 ). The 4- O -acetyl-3,6-di- O -benzyl isomer ( 18 ) of 11 was synthesized from 1β by a route involving selective, partial benzoylation, and then protection of O-4 as the 2-tetrahydropyranyl ether. As previously described, the 1-propenyl β-glycosides 3β , 11 , and 18 , and the tri- O -benzyl analog 5β , were converted in near-quantitative yield into the corresponding, substituted oxazolines by the action of mercuric chloride and mercuric oxide in boiling acetonitrile. An optimized procedure for this cyclization is given. The 1 H-n.m.r. spectra of the tri- O -acetyl ( 19 ) and the 4- O -acetyl-3,6-di- O -benzyl ( 21 ) oxazolines indicate a modified 0 S 2 , conformation for these compounds.

An improved synthesis of trehalose 6-mono and 6,6'--di-corynomycolates and related esters

A simplified synthesis of 6-mono- and 6,6-di-corynomycolate esters of alpha,alpha-trehalose, and related compounds, was achieved by coupling the (hydroxyl-protected) acids to the partially trimethylsilylated sugar in the presence of dicyclohexylcarbodiimide and 4-dimethylaminopyridine. As acid reactants, (2-RS,3-RS)-3-hydroxy-2-tetradecyloctadecanoic acid (DL-corynomycolic acid) and its 2RS,3SR diastereomer were prepared from methyl palmitate by sequential Claisen condensation, reduction, chromatographic separation, and saponification. Reaction with tert-butylchlorodimethylsilane (imidazole) gave the disubstituted ether-esters, which were converted into the required 3-tert-butyldimethylsilyl ethers by partial hydrolysis. 6-Linked monocorynomycolate was obtained in excellent yield (78%) from the reaction of the RS,SR acid with the known heptakis-O-(trimethylsilyl)trehalose, and in good yield from equimolar portions of RS,RS acid and hexakis-O-(trimethylsilyl)trehalose. An excess (2.5-molar portions) of the RS,RS acid gave the 6,6-diester (69%). The mono- and di-palmitate were similarly obtained from (Me3Si)6-trehalose. The mono (RS,RS)-(Me3Si)6-trehalose coupling product was partially resolved on a silica gel column into its RR and SS diastereomers, the former corresponding to the naturally occurring trehalose monocorynomycolate. All coupling products were deprotected to free trehalose esters by treatment first with K2CO3 in methanol, then tetrabutylammonium fluoride-trifluoracetic acid in oxolane.

O-Benzylated thio sugars. Derivatives of 2,3,6-tri-O-benzyl-1-thio-d-galactopyranose suitable for use in oligosaccharide synthesis

Abstract The 4- O -benzoyl ( 15a ) 4- O - p -nitrobenzoyl ( 15b ) derivatives of 2,3, 6-tri- O -benzyl-1-thio- d -galactopyranose were synthesized from allyl 2,6-di- O -benzyl-α- d -galactopyranoside ( 1 ). In the first stage of the synthesis the 3-position of 1 was benzylated by an indirect route, and also by the direct reaction (preferred) of benzyl bromide with the 3,4- O -dibutylstannylene intermediate 7 . The product 6 was sequentially isomerized (allyl → 1-propenyl), acylated at the 4-position, and hydrolyzed. The free sultars 11a and 11b were converted into the thio sugars by a standard sequence involving formation of the glycosyl halides 13a and 13b and the reaction of these with appropriate sulfur nucleophiles. A third derivative ( 29 ) of 2,3,6-tri- O -benzyl-1-thio- d -galactopyranose, having a 4- O -allyl protecting group, was similarly made from the corresponding normal sugar 25 . The key intermediate 22 , precursor to 25 , was prepared by two routes from methyl 2,3,6-tri- O -benzoyl-α- d -galactopyranoside (17) .

Partially benzylated oxazoline derivatives of 2-acetamido-2-deoxy-D-glucopyranose as “standardized intermediates” for oligosaccharide synthesis. preparation of disaccharides having the sequences β-D-GlcpNAc(1→x)-D-Gal and β-D-GlcpNAc(1→4)-D-GlcNAc

Abstract Three benzyl tri-O-benzyl-l-thio-β- D -galactopyranosides (5, 6, and 7) were prepared from the corresponding O-acyltri- O -benzyl- D -galactopyranosyl bromides (1a-c) via the benzylxanthates 2a-c and the fully protected benzyl thiogalactosides 3a-c. The α anomer (4) of 5 resulted from the reaction of bromide 1a with α-toluenethiol. Conditions were found for the successful coupling of O-acetyl-di-O-benzyl derivatives (8 and 13) of 2-methyl-(1,2-dideoxy-α- D -glucopyrano)-[2,1-d]-2-oxazoline to the thiogalactosides 5-7, and to a partially protected glycoside (16) or 2-acetamido-2-deoxy- D -glucose. The products were fully substituted disaccharides of 2-acetamido-2-deoxy-β- D -glucose linked 1→3 (9a), 1→6 (11a), 1→4 (14a), and 1→4 (17a), respectively. Cleavage of the single, temporary protecting group (O-acetyl) from these compounds gave partially deblocked disaccharides capable of chain extension from position 3′ (9b and 11b) or 4′ (14b and 17b).

Oligosaccharides from “standardized intermediates”. Synthesis of a branched tetrasaccharide glycoside isomeric with the blood-group B, type 2 determinant

Building block derivatives of the component monosaccharides were used to construct the tetrasaccharide glycoside 15, in which an alpha-D-Galp-(1 leads to 4)-D-Gal linkage replaces the alpha-(1 leads to 3) linkage of the human blood-group B, type 2, determinant structure. The initial coupling of 2-O-benzoyl-3,6-di-O-benzyl-4-O-(tetrahydropyran-2-yl)-alpha-D-galactopyranosyl chloride to allyl 2-acetamido-3,6-di-O-benzyl-2-deoxy-beta-D-glucopyranoside was followed by selective deprotection of the disaccharide product, either at O-4 (to give 8) or O-2 (to give 3). The conversion of 8 into 15 involved successive coupling with tetra-O-benzyl-alpha-D-galactopyranosyl bromide (8 leads to 11), O-debenzoylation at O-2 (11 leads to 12), coupling with tri-O-benzyl-alpha-L-fucopyranosyl bromide (12 leads to 14), and O-debenzylation by hydrogenolysis (14 leads to 15). Alternatively, 3 was alpha-L-fucosylated to give 6, and 6 was selectively deprotected at O-4 to give 7. However, attempts to alpha-D-galactosylate 7 were unsuccessful. The unsubstituted forms of the intermediate disaccharide (8) and trisaccharide (12) glycosides were obtained by appropriate deblocking procedures.

O-benzylated thio sugars: 2,3,4- and 2,4,6-tri-O-benzyl-1-thio-β-d-galactopyranose

Abstract The 2,3,4- (9) and 2,4,6-tribenzyl (19) ethers of 1-thio-β- d -galactopyranose were prepared from the corresponding O-benzylated normal (1-hydroxyl) sugars 4 and 15 via the sequence: normal sugar → diacetate → O-acetylglycosyl bromide → O-acetyl-glycosyl ethylxanthate → 1-thio sugar. 2,3,4-Tri-O-benzyl-α- d -galactopyranose (4) is most advantageously made from allyl 6-O-allyl-α- d -galactopyranoside (2) by a published synthesis. An improved synthesis of 2,4,6-tri-O-benzyl- d -galactopyranose (15) was devised; it involves the selective 3-O-benzoylation of allyl 2,6-di-O-benzyl-α- d -galactopyranoside (10).

A convenient preparation of 2-acetamido-2,6-dideoxy-d-glucose, some of its alkyl glycosides, and allyl 2-acetamido-2,6-dideoxy-α-d-galactopyranoside

Abstract Glycosides of 2-acetamido-2-deoxy- d -glucopyranose were treated with triphenylphosphine and N -bromosuccinimide to form the 6-bromo-6-deoxy derivatives. These, on hydrogenolysis in the presence of a palladium catalyst, yielded glycosides of 2-acetamido-2,6-dideoxy- d -glucopyranose ( N -acetyl- d -quinovosamine). When the benzyl β- d -glycoside was the starting material, the product was free N -acetyl- d -quinovosamine. The allyl 6-bromo-6-deoxy-α- and -β-glycosides, after partial benzoylation, were reduced by tributyltin hydride to allyl 2-acetamido-3- O -benzoyl-2,6-dideoxy-α- and -β- d -glucopyranoside. The α anomer was converted into allyl 2-acetamido-2,6-dideoxy-α- d -galactopyranoside (α glycoside of N -acetyl- d -fucosamine) by successive trifluoromethylsulfonylation, displacement with cesium benzoate, and O -debenzoylation.

“Standardized intermediates” for oligosaccharide synthesis. Precursors of β-linked, interior d-galactopyranose units having chain extension at position 4, or positions 4 and 2

Abstract Allyl 6- O -benzyl-3,4- O -isopropylidene-α-d-galactopyranoside (1) was used to prepare a series of 2- O -benzoyl-3,6-di- O -benzyl-α-d-galactopyranosyl halides carrying either a second benzoyl group (11, 17a) or a selectively removable, temporary protecting group (17b-d) at position 4. In one synthetic scheme, the 2-butenyl (crotyl) group was used for the transient protection of position 2, and the 2- O -benzoyl group was incorporated by selective acylation of a 2,4-diol (6) . In a more direct scheme, the 2- O -benzoyl group was introduced at the first step (1→12) . Selective benzylation of O-3 was accomplished by the action of α-bromotoluene on 3,4- O -dibutylstannylene derivatives (4 and 14) . Benzoyl, allyl, tert -butyldimethylsilyl, and tetrahydro-2-pyranyl groups, respectively, were incorporated at position 4 by derivatization of the otherwise fully substituted 1-propenyl glycoside 7 , or its precursor 15 . The fully substituted propenyl glycosides (8a-d) were converted into the 1-hydroxy compounds (9a-d) by mercuric ion-catalyzed hydrolysis, and thence directly into the chlorides (17a-d) by rection with hexamethylphosphorous triamide-carbon tetrachloride. The 2,4-di- O -benzoylated bromide 11 was made from 8a by a conventional sequence. On coupling to the 2-amino-2-deoxyglucoside 18 , it gave the disaccharide β-d-Gal p -(1→4)-d-GlcNAc in fully substituted form (19) .

Iodine as a reagent for the ready hydrolysis of prop-1-enyl glycosides, or their conversion into oxazolines

Iodine in oxolan with sutiable additives rapidly effects the hydrolysis of prop-1-enyl glycosides to free sugars, and the cyclization of prop-1-enyl β-glycosides of N-acylglucosamines to oxazolines.