US4024333A
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Synthesis of daunosamine hydrochloride from a D-mannose starting material
Assignee: United States Department of Health and Human Services
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Filing: 1976-06-22
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Granted: 1977-05-17
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Expires: 1996-06-22
Abstract
Abstract A method for synthesizing daunosamine hydrochloride from methyl α-D-mannopyranoside. The major features of the preparative route involve the formation of a 2-deoxy-3-keto intermediate, whose oxime is reduced with high stereoselectivity to the D-ribo-3-amino compound, followed by a stereospecific step late in the sequence to introduce the terminal C-methyl group with inversion at C-5, to generate the required L-lyxo stereochemistry. The synthesis procedure affords daunosamine hydrochloride in 40% overall yield, with no chromatographic procedures for isolation being required in any of the steps.
Inventors
- 👤 Derek Horton
- 👤 Wolfgang F. Weckerle
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-28 22:08
CPC Classifications
C; C07; C07H; C07H5/00; C07H5/04; C07H5/06; C07H15/00; C07H15/02; C07H15/04
Claims Analysis
Total Claims: 6
Claim 1
Independent Claim
160 words
A method for the synthesis of daunosamine hydrochloride from methyl α-D-mannopyranoside, which comprises the steps of: a. benzylidenting said methyl α-D-mannopyranoside to the 2,3:4,6-dibenzylidene acetal with α,α-dimethoxytoluene; b. converting said 2,3:4,6-dibenzylidene acetal into the 4,6-O-benzylidene-2-deoxy-3-keto compound with butyllithium; c. oximating the 3-keto group to the 3-oxime group with hydroxylamine; d. reducing said 3-oxime group to the 3-amino group with lithium aluminum hydride; e. acetylating said 3-amino group to the 3-acetamido group with acetic anhydride and recovering from the reaction mixture the 4,6-O-benzylidene-D-ribo-3-acetamido compound; f. converting said 4,6-O-benzylidene-D-ribo-3-acetamido compound into the 4-O-benzoyl-6-bromo-6-deoxy compound with N-bromosuccinimide; g. dehydrobrominating said 4-O-benzoyl-6-bromo compound to the 4-O-benzoyl-5,6-unsaturated compound with silver fluoride; h. debenzoylating said 4-O-benzoyl-5,6-unsaturated compound to the 4-hydroxy-5,6-unsaturated compound by catalytic transesterification with sodium methoxide; i. stereospecifically hydrogenating said 4-hydroxy-5,6-unsaturated compound in the presence of palladium-on-barium sulfate to give methyl N-acetyl-β-daunosaminide; j. N-deacylating said methyl N-acetyl-β-daunosaminide with aqueous barium hydroxide; and k. hydrolyzing the N-deacylated compound with aqueous hydrochloric acid to give daunosamine hydrochloride.
Claim 2
Independent Claim
160 words
A method for the synthesis of daunosamine hydrochloride from methyl α-D-mannopyranoside, which comprises the steps of: a. benzylidenting said methyl α-D-mannopyranoside to the 2,3:4,6-dibenzylidene acetal with α,α-dimethoxytoluene; b. converting said 2,3:4,6-dibenzylidene acetal into the 4,6-O-benzylidene-2-deoxy-3-keto compound with butyllithium; c. oximating the 3-keto group to the 3-oxime group with hydroxylamine; d. reducing said 3-oxime group to the 3-amino group with lithium aluminum hydride; e. acetylating said 3-amino group to the 3-acetamido group with acetic anhydride and recovering from the reaction mixture the 4,6-O-benzylidene-D-ribo-3-acetamido compound; f. converting said 4,6-O-benzylidene-D-ribo-3-acetamido compound into the 4-O-benzoyl-6-bromo-6-deoxy compound with N-bromosuccinimide; g. dehydrobrominating said 4-O-benzoyl-6-bromo compound to the 4-O-benzoyl-5,6-unsaturated compound with silver fluoride; h. debenzoylating said 4-O-benzoyl-5,6-unsaturated compound to the 4-hydroxy-5,6-unsaturated compound by catalytic transesterification with sodium methoxide; i. stereospecifically hydrogenating said 4-hydroxy-5,6-unsaturated compound in the presence of palladium-on-barium sulfate to give methyl N-acetyl-β-daunosaminide; j. N-deacylating said methyl N-acetyl-β-daunosaminide with aqueous barium hydroxide; and k. hydrolyzing the N-deacylated compound with aqueous hydrochloric acid to give daunosamine hydrochloride.
Claim 3
Dependent Claim
51 words
The method of claim 1, wherein said 4,6-O-benzylidene-D-ribo-3-acetamido compound is recovered from said reaction mixture in step (e) by mixing said reaction mixture with toluene to thereby precipitate the D-arabino diastereoisomer of said 4,6-O-benzylidene-D-ribo-3-acetamido compound, separating the precipitate from said reaction mixture, and evaporating the mother liquor of said reaction mixture.
Claim 4
Dependent Claim
24 words
The method of claim 2, wherein the mixing of said reaction mixture with toluene is carried out at a temperature of about 0° C.
Claim 5
Dependent Claim
43 words
The method of claim 1, wherein the conversion of said 2,3:4,6-dibenzylidene acetal into said 4,6-O-benzylidene-2-deoxy-3-keto compound in step (b) is carried out at a temperature below -30° C, and the molar ratio of said butyllithium to said 2,3:4,6-dibenzylidene acetal is at least 2:1.
Claim 6
Dependent Claim
24 words
The method of claim 4, wherein said temperature is within the range of from -30° to -55° C, and said molar ratio is 2.2:1.
References Cited (Backward Citations)
No citation records indexed.
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