Contributions to the synthesis of higher hetero-oligosaccharides and anisomycin antibiotics.
Creators: name: Wang, Sho-Nong.
Publisher: name: Université d'Ottawa / University of Ottawa
Year: 1996
Subjects: subject: Chemistry, Organic.

description: Section 1. Improvements were made in the procedures for the preparation of hexa-O-acetyllactal and of the lactosamine donors 3,6-di-O-acetyl-4-O-(2,3,4,6-tetra-O-acetyl-$ \beta$-D-galactopyranosyl)-2-deoxy-2-phthalimido-$ \beta$-D-glucopyranostl chloride, bromide, and trichloroacetimidate. In particular, introduction of halogen by means of dichloromethyl methyl ether and trimethylsilyl bromide was found to be superior to previous methods. The new disaccharide methyl 2-benzamido-4,6-O-benzylidene-2-deoxy-3-O-(2,3,4,6-tetra-O-acetyl-$ \beta$-D-galactopyranosyl)-$\alpha$-D-glucopyranoside was synthesized by the Koenigs-Knorr method and was converted, in a one-pot acetolysis reaction, into phenyl-(1,2-dideoxy-4,6-di-O-acetyl-3-O-(2,3,4,6-tetra-O-acetyl-$\beta$-D-galactopyranosyl)-$ \alpha$-D-glucopyrano) (2$\sp\prime,1\sp \prime$:4,5) -2-oxazolinium acetate, a new donor of the lacto-N-biosyl unit in glycosylations. Furthermore, it was discovered that trimethylsilyl triflate-promoted transfer of a 3-O-benzylated D-galactose 1-acetate to OH-3 of a partially blocked methyl N-benzoylglucosaminide led not only to formation of the expected disaccharide linkage but at the same time converted the acceptor glycoside into an oxazoline, thus producing a new lacto-N-biose donor having a temporarily blocked 3$\sp\prime$-position, which should be useful for the design of block syntheses of higher heterosaccharides. Peracetylated 2-azido-2-deoxylactose and the corresponding 1,3,6,2$\sp\prime,6\sp\prime$-pentaacetate (a new lactosamine acceptor equivalent) were synthesized from hexaacetyllactal by the azidonitration method, and a number of other lactosamine and lactose acceptors having unprotected OH-3$\sp\prime$ and OH-4$\sp\prime$ groups were prepared by established procedures. Methyl 4,6-di-O-acetyl-2-benzamido-2-deoxy-3-O-(2,4,6-tri-O-benzoyl-3-O-benzyl-$\beta$-D-galactopyranosyl)-$ \alpha$-D-glucopyranoside was synthesized, to be used as a lacto-N-biose acceptor after deprotection of O-3$\sp\prime.$ Three similarly substituted methyl glycosides of 3-$\beta$-D-galactopyranosyl-D-glucose ("isolactose") were prepared by condensations of various D-galactopyranosyl bromides with methyl 2-O-benzoyl-4,6-O-benzylidene-$ \alpha$-D-glucopyranoside in order to obtain molecules that may serve as "isolactose" acceptors after deprotection at O-3$\sp\prime.$ Observations concerning the stability of benzyl ethers in these reactions were recorded. Treatment of 1,3,4,6-tetra-O-acetyl-2-deoxy-2-phthalimido-$\beta$-D-glucopyranose with tributyltin benzyloxide in the presence of stannic chloride did not lead to the expected benzyl glycoside but gave in high yield a new disaccharidic coupling product, i.e., 2,2$\sp\prime$-dideoxy-2,2$\sp\prime$-diphthalimido-$ \beta,\beta$-trehalose hexaacetate, and a minor product which is possibly its $\alpha,\beta$-anomer. Section 2. 1-Amino-1-deoxy-D-xylitol hydrochloride was sequentially N-carbobenzyloxylated and isopropylidenated. The 1-benzyloxycarbonylamido-1-deoxy-2,3:4,5-di-O-isopropylidene-D-xylitol so obtained was subjected to partial hydrolysis for removal of the 4,5-acetonide, followed by periodate glycol cleavage to give 4-benzyloxycarbonylamido-2,3-O-isopropylidene-L-erythrose. This aldehydo sugar was reacted with p-methoxyphenylnitromethane to furnish 5-benzyloxycarbonylamido-3,4-O-isopropylidene-1-(4-methox yphenyl)-1-nitropentane-2,3,4-triol. Its 2-acetate was subjected to dehydroacetoxylation, giving the corresponding nitroalkene, 5-benzyloxycarbonylamido-3,4-O-isopropylidene-1-(4-methoxyphenyl)-1-nitro-1-pentene-3,4-diol. Deacetonation then gave the corresponding free diol. Attempts to effect cyclizing Michael addition in these nitroalkenes, to construct the 2-(p-methoxybenzyl)-substituted pyrrolidine-3,4-diol structure of anisomycin have so far been unsuccessful.