(R)-tert-butoxycarbonylamino-fluorenylmethoxycarbonyl-glycine from (S)-benzyloxycarbonyl-serine or from papain resolution of the corresponding amide or methyl ester

Michal Sypniewski, B. Penke, Lajos Simon, Jean Rivier

Research output: Contribution to journalArticle

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Abstract

The enantiospecific synthesis of (R)-Boc-(Fmoc)-aminoglycine 7 was achieved. (S)-Cbz-serine 1 was reacted with diphenylphosphoryl azide in the presence of triethylamine to yield cyclic(S) carbamate 2. The ring nitrogen of 2 was protected with a Boc group. (3). The cyclic carbamate of 3 was hydrolyzed with benzyltrimethylammonium hydroxide to yield the (R)-enantiomer of alcohol 4. The oxidation of 4 with pyridinium dichromate yielded the enantiomerically pure (97% ee) (R)-Boc-(Cbz)-aminoglycine 5, which was converted to 7 with retention, of optical purity. Similarly, starting from (S)-Boc-serine 9, cyclic (S) carbamate 10 was obtained. The ring nitrogen of 10 was protected with a Cbz group (11) with retention of configuration. The cyclic carbamate of 11 was base hydrolyzed to yield 12, the (S)-enantiomer alcohol. Independently, Boc-(Fmoc)-aminoglycine amide 13 and Boc-(Fmoc)-aminoglycine methyl ester. 14 were resolved using papain. The stereochemistry of the isolated acid was determined to be (R) by coelution on HPLC of its deriyative with Marfey's reagent and that of an authentic sample (7) obtained by enantiospecific synthesis.

Original languageEnglish
Pages (from-to)6595-6600
Number of pages6
JournalJournal of Organic Chemistry
Volume65
Issue number20
DOIs
Publication statusPublished - Oct 6 2000

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Papain
Carbamates
Amides
Glycine
Esters
Enantiomers
Nitrogen
Alcohols
Stereochemistry
Serine
Oxidation
Acids
benzyloxycarbonylserine
tert-butoxycarbonylamino-fluorenylmethoxycarbonylacetic acid

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

(R)-tert-butoxycarbonylamino-fluorenylmethoxycarbonyl-glycine from (S)-benzyloxycarbonyl-serine or from papain resolution of the corresponding amide or methyl ester. / Sypniewski, Michal; Penke, B.; Simon, Lajos; Rivier, Jean.

In: Journal of Organic Chemistry, Vol. 65, No. 20, 06.10.2000, p. 6595-6600.

Research output: Contribution to journalArticle

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abstract = "The enantiospecific synthesis of (R)-Boc-(Fmoc)-aminoglycine 7 was achieved. (S)-Cbz-serine 1 was reacted with diphenylphosphoryl azide in the presence of triethylamine to yield cyclic(S) carbamate 2. The ring nitrogen of 2 was protected with a Boc group. (3). The cyclic carbamate of 3 was hydrolyzed with benzyltrimethylammonium hydroxide to yield the (R)-enantiomer of alcohol 4. The oxidation of 4 with pyridinium dichromate yielded the enantiomerically pure (97{\%} ee) (R)-Boc-(Cbz)-aminoglycine 5, which was converted to 7 with retention, of optical purity. Similarly, starting from (S)-Boc-serine 9, cyclic (S) carbamate 10 was obtained. The ring nitrogen of 10 was protected with a Cbz group (11) with retention of configuration. The cyclic carbamate of 11 was base hydrolyzed to yield 12, the (S)-enantiomer alcohol. Independently, Boc-(Fmoc)-aminoglycine amide 13 and Boc-(Fmoc)-aminoglycine methyl ester. 14 were resolved using papain. The stereochemistry of the isolated acid was determined to be (R) by coelution on HPLC of its deriyative with Marfey's reagent and that of an authentic sample (7) obtained by enantiospecific synthesis.",
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N2 - The enantiospecific synthesis of (R)-Boc-(Fmoc)-aminoglycine 7 was achieved. (S)-Cbz-serine 1 was reacted with diphenylphosphoryl azide in the presence of triethylamine to yield cyclic(S) carbamate 2. The ring nitrogen of 2 was protected with a Boc group. (3). The cyclic carbamate of 3 was hydrolyzed with benzyltrimethylammonium hydroxide to yield the (R)-enantiomer of alcohol 4. The oxidation of 4 with pyridinium dichromate yielded the enantiomerically pure (97% ee) (R)-Boc-(Cbz)-aminoglycine 5, which was converted to 7 with retention, of optical purity. Similarly, starting from (S)-Boc-serine 9, cyclic (S) carbamate 10 was obtained. The ring nitrogen of 10 was protected with a Cbz group (11) with retention of configuration. The cyclic carbamate of 11 was base hydrolyzed to yield 12, the (S)-enantiomer alcohol. Independently, Boc-(Fmoc)-aminoglycine amide 13 and Boc-(Fmoc)-aminoglycine methyl ester. 14 were resolved using papain. The stereochemistry of the isolated acid was determined to be (R) by coelution on HPLC of its deriyative with Marfey's reagent and that of an authentic sample (7) obtained by enantiospecific synthesis.

AB - The enantiospecific synthesis of (R)-Boc-(Fmoc)-aminoglycine 7 was achieved. (S)-Cbz-serine 1 was reacted with diphenylphosphoryl azide in the presence of triethylamine to yield cyclic(S) carbamate 2. The ring nitrogen of 2 was protected with a Boc group. (3). The cyclic carbamate of 3 was hydrolyzed with benzyltrimethylammonium hydroxide to yield the (R)-enantiomer of alcohol 4. The oxidation of 4 with pyridinium dichromate yielded the enantiomerically pure (97% ee) (R)-Boc-(Cbz)-aminoglycine 5, which was converted to 7 with retention, of optical purity. Similarly, starting from (S)-Boc-serine 9, cyclic (S) carbamate 10 was obtained. The ring nitrogen of 10 was protected with a Cbz group (11) with retention of configuration. The cyclic carbamate of 11 was base hydrolyzed to yield 12, the (S)-enantiomer alcohol. Independently, Boc-(Fmoc)-aminoglycine amide 13 and Boc-(Fmoc)-aminoglycine methyl ester. 14 were resolved using papain. The stereochemistry of the isolated acid was determined to be (R) by coelution on HPLC of its deriyative with Marfey's reagent and that of an authentic sample (7) obtained by enantiospecific synthesis.

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