(R)-tert-Butoxycarbonylamino-fluorenylmethoxycarbonyl-glycine from (S)-benzyloxycarbonyl-serine or from papain resolution of the corresponding amide or methyl ester.
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 derivative with Marfey's reagent and that of an authentic sample (7) obtained by enantiospecific synthesis.
Sypniewski
M
M
Clayton Foundation Laboratories for Peptide Biology, The Salk Institute, La Jolla, California 92037, USA.
Penke
B
B
Simon
L
L
Rivier
J
J
D000577:Amides / Q000737:chemistry; D004952:Esters / Q000737:chemistry; D005998:Glycine / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D006868:Hydrolysis; D010206:Papain / Q000737:chemistry*; D012694:Serine / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D013237:Stereoisomerism
D000577:Amides; D004952:Esters; C416068:tert-butoxycarbonylamino-fluorenylmethoxycarbonylacetic acid; C416067:benzyloxycarbonylserine; D012694:Serine; D010206:Papain; D005998:Glycine