H2NJAph p+ - American Chemical Society


Aug 15, 1989 - erythro - and threo -L-&Hydroxyornithine from an Improved Vinylglycine ..... benzene (500 mL) was added cupric acetate monohydrate (2.2...
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J. Org. Chem. 1991,56, 728-731

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Stereochemical Correlation of Proclavaminic Acid and Syntheses of erythro - and threo -L-&Hydroxyornithinefrom an Improved Vinylglycine Synthon Walter J. Krol, Shi-shan Mao, Diana L. Steele, and Craig A. Townsend* Department of Chemistry, The Johns Hopkins University, Baltimore, Maryland 21218

Received August 15, 1989 The Hanessian method to prepare the N-Cbz-L-vinylglycine methyl ester has been improved to obtain reproducibility an alternately protected version of this useful synthon in optically pure, crystalline form. A nitrone cycloaddition route has been developed to synthesizeerythro- and threo-L-&hydroxyornithhehaving stereoisomeric purities of >99%. A parallel route described recently, proceeding from Hanessian’s methyl vinylglycinate,gives these oxidatively modified a-aminoacids in inferior enantiomeric excess owing to partial racemization that occurs in the oxidative decarboxylation to the protected vinylglycines themselves. The intermediate isomlidhe generated in the present synthesis was separately converted to proclavaminic acid, a key intermediate in the biosynthesis of the /3-lactamaseinhibitor clavulanic acid, and ita absolute configuration was established as bthreo by unambiguous correlation to L-glutamic acid. L-Ornithine (1) has been established to be one of two fundamental building blocks drawn from primary metabolism in Streptomyces clavuligerus to construct the plactamase inhibitor clavulanic acid (2).l The oxidation state at C-2 of the latter suggested that &hydroxyornithine (3) might be an intermediate in the biosynthetic pathway.

H

2

N

v

~

~

2

I

COOH

0 Ph

+

R

H

N

p

-

COOR

COOR

I

8

9 1

COOH

COOH

3

2

1

Scheme I

0 c

C b z H N V C O O H C b * H N 1COOMe /VS,Me

0

COOMe

COOH

4

5

6

Based upon the separate observations of Doyle2 and 13 Ganem,3 racemic erythro- and threo-[5-14C]-/3-hydroxyornithine, 12 and 13, respectively, were prepared as shown l1 in Scheme I where [14C]formaldehydeprovided a ready O-NnPh source of radiolabel. Unfortunately, attempted incorpoR”m!!+ ration of these oxidatively modified amino acids under whole-cell conditions that had been used successfully COOBn COOBn earlier’ failed to show uptake of the labeled material (