A convenient synthesis of 2S, 3S‐[3‐2H]‐serine and 2S, 3R‐[2, 3‐2H2]‐serine

Lawrence Slieker, Stephen Benkovic

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Both 2S, 3R‐[2, 3‐2H2]‐serine 5 and 2S, 3S‐[3‐2H]‐serine 6 have been prepared from (E)‐methyl‐[2, 3.‐2H2]‐acrylate and (Z)‐ethyl‐[3‐2H]‐acrylate, respectively. The acrylate esters were converted to a mixture of isomeric bromohydrins by treatment with N‐bromoacetamide. The ratio of 2‐bromo‐3‐hydroxy species to the 2‐hydroxy‐3‐bromo isomer was approximately 3:1. Conversion to the corresponding azido alcohols by treatment with NaN3 followed by catalytic reduction over Pd gave the alkyl esters of serine and isoserine. Purification and hydrolysis yielded serine in typically 20–25% yield from methyl or ethyl acrylate. Resolution was accomplished enzymatically by hog kidney acylase I treatment of the N‐acetyl derivative. Absolute configuration was determined by 1H NMR and the ratio of proton intensity in the diastereotopic positions at C–3 were measured to be HS/HR = 11 for 5 and HR/HS = 4.4 for 6.

Original languageEnglish (US)
Pages (from-to)647-657
Number of pages11
JournalJournal of Labelled Compounds and Radiopharmaceuticals
Volume19
Issue number5
DOIs
StatePublished - Jan 1 1982

Fingerprint

Serine
HS 6
Esters
Sodium Azide
Isomers
Purification
Protons
Hydrolysis
Alcohols
Nuclear magnetic resonance
Derivatives
Kidney
ethyl acrylate
acrylic acid

All Science Journal Classification (ASJC) codes

  • Analytical Chemistry
  • Biochemistry
  • Radiology Nuclear Medicine and imaging
  • Drug Discovery
  • Spectroscopy
  • Organic Chemistry

Cite this

@article{1f5f7ffd6f4946359486bc378586e68e,
title = "A convenient synthesis of 2S, 3S‐[3‐2H]‐serine and 2S, 3R‐[2, 3‐2H2]‐serine",
abstract = "Both 2S, 3R‐[2, 3‐2H2]‐serine 5 and 2S, 3S‐[3‐2H]‐serine 6 have been prepared from (E)‐methyl‐[2, 3.‐2H2]‐acrylate and (Z)‐ethyl‐[3‐2H]‐acrylate, respectively. The acrylate esters were converted to a mixture of isomeric bromohydrins by treatment with N‐bromoacetamide. The ratio of 2‐bromo‐3‐hydroxy species to the 2‐hydroxy‐3‐bromo isomer was approximately 3:1. Conversion to the corresponding azido alcohols by treatment with NaN3 followed by catalytic reduction over Pd gave the alkyl esters of serine and isoserine. Purification and hydrolysis yielded serine in typically 20–25{\%} yield from methyl or ethyl acrylate. Resolution was accomplished enzymatically by hog kidney acylase I treatment of the N‐acetyl derivative. Absolute configuration was determined by 1H NMR and the ratio of proton intensity in the diastereotopic positions at C–3 were measured to be HS/HR = 11 for 5 and HR/HS = 4.4 for 6.",
author = "Lawrence Slieker and Stephen Benkovic",
year = "1982",
month = "1",
day = "1",
doi = "10.1002/jlcr.2580190505",
language = "English (US)",
volume = "19",
pages = "647--657",
journal = "Journal of Labelled Compounds and Radiopharmaceuticals",
issn = "0362-4803",
publisher = "John Wiley and Sons Ltd",
number = "5",

}

A convenient synthesis of 2S, 3S‐[3‐2H]‐serine and 2S, 3R‐[2, 3‐2H2]‐serine. / Slieker, Lawrence; Benkovic, Stephen.

In: Journal of Labelled Compounds and Radiopharmaceuticals, Vol. 19, No. 5, 01.01.1982, p. 647-657.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A convenient synthesis of 2S, 3S‐[3‐2H]‐serine and 2S, 3R‐[2, 3‐2H2]‐serine

AU - Slieker, Lawrence

AU - Benkovic, Stephen

PY - 1982/1/1

Y1 - 1982/1/1

N2 - Both 2S, 3R‐[2, 3‐2H2]‐serine 5 and 2S, 3S‐[3‐2H]‐serine 6 have been prepared from (E)‐methyl‐[2, 3.‐2H2]‐acrylate and (Z)‐ethyl‐[3‐2H]‐acrylate, respectively. The acrylate esters were converted to a mixture of isomeric bromohydrins by treatment with N‐bromoacetamide. The ratio of 2‐bromo‐3‐hydroxy species to the 2‐hydroxy‐3‐bromo isomer was approximately 3:1. Conversion to the corresponding azido alcohols by treatment with NaN3 followed by catalytic reduction over Pd gave the alkyl esters of serine and isoserine. Purification and hydrolysis yielded serine in typically 20–25% yield from methyl or ethyl acrylate. Resolution was accomplished enzymatically by hog kidney acylase I treatment of the N‐acetyl derivative. Absolute configuration was determined by 1H NMR and the ratio of proton intensity in the diastereotopic positions at C–3 were measured to be HS/HR = 11 for 5 and HR/HS = 4.4 for 6.

AB - Both 2S, 3R‐[2, 3‐2H2]‐serine 5 and 2S, 3S‐[3‐2H]‐serine 6 have been prepared from (E)‐methyl‐[2, 3.‐2H2]‐acrylate and (Z)‐ethyl‐[3‐2H]‐acrylate, respectively. The acrylate esters were converted to a mixture of isomeric bromohydrins by treatment with N‐bromoacetamide. The ratio of 2‐bromo‐3‐hydroxy species to the 2‐hydroxy‐3‐bromo isomer was approximately 3:1. Conversion to the corresponding azido alcohols by treatment with NaN3 followed by catalytic reduction over Pd gave the alkyl esters of serine and isoserine. Purification and hydrolysis yielded serine in typically 20–25% yield from methyl or ethyl acrylate. Resolution was accomplished enzymatically by hog kidney acylase I treatment of the N‐acetyl derivative. Absolute configuration was determined by 1H NMR and the ratio of proton intensity in the diastereotopic positions at C–3 were measured to be HS/HR = 11 for 5 and HR/HS = 4.4 for 6.

UR - http://www.scopus.com/inward/record.url?scp=0019905570&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0019905570&partnerID=8YFLogxK

U2 - 10.1002/jlcr.2580190505

DO - 10.1002/jlcr.2580190505

M3 - Article

AN - SCOPUS:0019905570

VL - 19

SP - 647

EP - 657

JO - Journal of Labelled Compounds and Radiopharmaceuticals

JF - Journal of Labelled Compounds and Radiopharmaceuticals

SN - 0362-4803

IS - 5

ER -