Alanosine

合成路线:The reaction of methyl 2-acetamido-3-chloropropionate (IX) with hydroxylamine followed by hydrolysis with concentrated HCl gives D,L-2-amino-3-hydroxyaminopropionic acid (VIII),which is benzoylated with benzoyl chloride in aqueous 10% NaOH yielding D,L-2-benzoylamino-3-(N-benzoyl-N-hydroxyamino)propionic acid (X).The resolution of (X) into optical isomers by treatment with cinchonine in ethanol,followed by treatment with 20% HCl at 100 C affords L-2-amino-3-hydroxyaminopropionic acid (L)-(VIII),which is nitrosated with NaNO2 and HCl.Racemic alanosine can be obtained by nitrosation of D,L-2-amino-3-hydroxyaminopropionic acid (VIII) obtained before.

参考文献标题:
文献作者:
参考来源:US 3823186


合成路线:Ethyl 2,3-dibromopropionate (I) is condensed with N-tosyl-O-benzylhydroxylamine (A) by means of NaOEt in ethanol to give after a treatment with ammonia,propionic acid (II),which is detosylated by treatment with phenol and 36% HBr- yielding D,L-2-amino-3-(benzyloxyamino)propionic acid (III).The benzoylation of (III) with N-benzoyloxysuccinimide (B) by means of Triton B - in methanol affords D,L-2-benzoylamino-3-benzyloxyaminopropionic acid (IV),which is resolved into its optical isomers by treatment with aniline (C) and papain in 0.5M NaOH - 0.5M citric acid and L-cysteine hydrochloride; L-2-benzoylamino-3-benzyloxyaminopropionanilide (L)-(V) was isolated.The benzoylation of (L)-(V) with benzoyl chloride (D) in pyridine affords L-2-benzoylamino-3-(N-benzoyl-N-benzyloxyamino)propionanilide (L)-(VI),which is debenzylated by hydrogenation with H2 over Pd/C in methanol giving L-2-benzoylamino-3-(N-benzoyl-N-hydroxyamino)propionanilide (L)-(VII).The protecting groups of (L)-(VII) are eliminated by treatment with 6M HCl at 90-5 C yielding L-2-amino-3-hydroxyaminopropionic acid (L)-(VIII),which is finally nitrosated with NaNO2 and HCl.

参考文献标题:Synthesis of alanosine
文献作者:Yoshikazu,I.; et al.
参考来源:Bull Chem Soc Jpn 1973,461847-50


合成路线:The reaction of methyl 2-acetamido-3-chloropropionate (IX) with hydroxylamine followed by hydrolysis with concentrated HCl gives D,L-2-amino-3-hydroxyaminopropionic acid (VIII),which is benzoylated with benzoyl chloride in aqueous 10% NaOH yielding D,L-2-benzoylamino-3-(N-benzoyl-N-hydroxyamino)propionic acid (X).The resolution of (X) into optical isomers by treatment with cinchonine in ethanol,followed by treatment with 20% HCl at 100 C affords L-2-amino-3-hydroxyaminopropionic acid (L)-(VIII),which is nitrosated with NaNO2 and HCl.Racemic alanosine can be obtained by nitrosation of D,L-2-amino-3-hydroxyaminopropionic acid (VIII) obtained before.

参考文献标题:Synthesis of homolog of the antibiotic alanosine
文献作者:Lancini,G.C.; et al.
参考来源:Farmaco 1969,24(2),169-178


合成路线:Ethyl 2,3-dibromopropionate (I) is condensed with N-tosyl-O-benzylhydroxylamine (A) by means of NaOEt in ethanol to give after a treatment with ammonia,propionic acid (II),which is detosylated by treatment with phenol and 36% HBr- yielding D,L-2-amino-3-(benzyloxyamino)propionic acid (III).The benzoylation of (III) with N-benzoyloxysuccinimide (B) by means of Triton B - in methanol affords D,L-2-benzoylamino-3-benzyloxyaminopropionic acid (IV),which is resolved into its optical isomers by treatment with aniline (C) and papain in 0.5M NaOH - 0.5M citric acid and L-cysteine hydrochloride; L-2-benzoylamino-3-benzyloxyaminopropionanilide (L)-(V) was isolated.The benzoylation of (L)-(V) with benzoyl chloride (D) in pyridine affords L-2-benzoylamino-3-(N-benzoyl-N-benzyloxyamino)propionanilide (L)-(VI),which is debenzylated by hydrogenation with H2 over Pd/C in methanol giving L-2-benzoylamino-3-(N-benzoyl-N-hydroxyamino)propionanilide (L)-(VII).The protecting groups of (L)-(VII) are eliminated by treatment with 6M HCl at 90-5 C yielding L-2-amino-3-hydroxyaminopropionic acid (L)-(VIII),which is finally nitrosated with NaNO2 and HCl.

合成路线:The reaction of methyl 2-acetamido-3-chloropropionate (IX) with hydroxylamine followed by hydrolysis with concentrated HCl gives D,L-2-amino-3-hydroxyaminopropionic acid (VIII),which is benzoylated with benzoyl chloride in aqueous 10% NaOH yielding D,L-2-benzoylamino-3-(N-benzoyl-N-hydroxyamino)propionic acid (X).The resolution of (X) into optical isomers by treatment with cinchonine in ethanol,followed by treatment with 20% HCl at 100 C affords L-2-amino-3-hydroxyaminopropionic acid (L)-(VIII),which is nitrosated with NaNO2 and HCl.Racemic alanosine can be obtained by nitrosation of D,L-2-amino-3-hydroxyaminopropionic acid (VIII) obtained before.
参考文献标题:Alanosine
文献作者:Serradell,M.N.; Casta馿r,J.; Cabanillas,F.; Blancafort,P.
参考来源:Drugs Fut 1979,4(7),469