Roderick Hanna

Convenient syntheses of L-digitoxose, L-cymarose, and L-ristosamine

Methyl 2,3-O-benzylidene-6-deoxy-4-O-(2-methoxyethoxymethyl)-α-L-mannopyranoside (10) and the 4-O-(methoxymethyl) analogue (11) reacted with butyl-lithium to give the 4-O-substituted methyl 2,6-dideoxy-α-L-erythro- hexopyranosid-3-uloses (12) and (13), respectively. Appropriate transformations on these keto-sugars afforded practical syntheses of 2,6-dideoxy-L-ribo-hexopyranose (L-digitoxose)(15), its 3-O-methyl analogue (17)(L-cymarose), and 3-acetamido-2,3,6-trideoxy-L-ribo-hexose (N-acetyl-L-ristosamine).A slight amendment to one of the sugar residues in published structures of the orthosomycin antibiotics flambamycin and avilamycins is indicated.

Higher-carbon sugars. Part 2. The synthesis of some decitols via the osmylation of unsaturated precursors

Sharpless epoxidation of (E)-8,9-dideoxy-1,2 : 3,4 : 6,7-tri-O-isopropylidene-α-D-threo-D-galacto-dec-8-enopyranose (3) with di-isopropyl L-(+)-tartrate as the chiral auxiliary furnished a mixture of 8,9anhydro-1,2 : 3,4 : 6,7-tri-O-isopropylidene-β-L-galacto-D-galacto-decopyranose (10)(isolated in 63% yield) and the α-D-ido-galacto isomer (11) in the ratio ∼5 : 1. Base-catalysed hydrolysis of the epoxy alcohol (10) gave, via preferential ring-opening of the Payne-rearrangement product (12), 1,2 : 3,4 : 6,7-tri -O-isopropylidene-α-D-altro-D-galacto-decopyranose (8), which yielded Daltro-D-galacto-decitol (13) following acidic hydrolysis and reduction of the resulting decose. The epoxy alcohol (11) was the principal product obtained on Sharpless epoxidation of the decenopyranose (3) with di-isopropyl D-(–)-tartrate as the chiral auxiliary, and was similarly transformed into L-gluco-D-galacto-decitol (L-galacto-D-gulo-decitol)(16). The same strategy was also used in the synthesis of D-gluco-D-galacto-decitol (L-galacto-L-gulo-decitol)(1) and L-altro-D-galacto-decitol (25) from (E)-8,9-dideoxy-1,2 : 3,4 : 6,7-tri-O-isopropylidene-β-L-threo-D-galacto-dec-8-enopyranose (18).

Higher-carbon sugars. Part 1. The synthesis of some octose sugars via the osmylation of unsaturated precursors

Titanium-catalysed asymmetric epoxidation of (E)-6,7-dideoxy-1,2:3,4-di-O-isopropylidene-α-D-galacto-oct-6-enopyranose (1) with di-isopropyl L-(+)-tartrate afforded 6,7-anhydro-1,2:3,4-di-O-isopropylidene-β-L-threo-D-galacto-octopyranose (4), which was identified by its conversion on basic hydrolysis into 1,2:3,4-di-O-isopropylidene-α-D-erythro-D-galacto-octopyranose (6)via preferential ring-opening of the Payne-rearrangement product (5) at the terminal position. Oxidation of (1) with m-chloroperbenzoic acid gave principally the isomeric epoxy alcohol (8), which basic hydrolysis similarly transformed into 1,2:3,4-di-O-isopropylidene-β-L-erythro-D-galacto-octopyranose (10). The latter sequence of reactions also yielded 1,2:3,4-di-O-isopropylidene-α-D-threo-D-galacto-octopyranose (3) from (Z)-6,7-dideoxy-1,2:3,4-di-O-isopropylidene-α-D-galacto-oct-6-enopyranose (12). D-erythro-D-galacto-Octitol (7), L-erythro-D-galacto-octitol (11), and D-threo-D-galacto-octitol (16) are accessible from the protected octoses (6), (10), and (3), respectively.

Branched-chain sugars. Part 16. The synthesis of a derivative of 3-amino-2,3,6-trideoxy-3-C-methyl-L-xylo-hexopyranose, the novel branched-chain amino sugar of antibiotic A35512B

Methyl 2,6-dideoxy-4-O-methoxymethyl-α-L-erythro-hexopyranosid-3-ulose (1) reacted with potassium cyanide under equilibrating conditions to give methyl 3-C-cyano-2,6-dideoxy-4-O-methoxymethyl-α-L-arabino-hexopyranoside (11). The mesylate (12) derived from this cyanohydrin was converted by established procedures, although not without difficulty, into methyl 3-acetamido-2,3,6-trideoxy-4-O-methoxymethyl-3-C-methyl-α-L-ribo-hexopyranoside (17), which was then converted in a straightforward manner into methyl 3-acetamido-2,3,6-trideoxy-3-C-methyl-α-L-ribo-hexopyranoside (20). Inversion of the configuration at C-4 of the latter compound, by means of an oxidation–reduction sequence, yielded methyl 3-acetamido-2,3,6-trideoxy-3-C-methyl-α-L-xylo-hexopyranoside (22), a derivative of the novel branched-chain amino sugar found in antibiotic A35512B.