Synthesis of [3,3‐D2]4‐hydroxy‐1‐(3‐pyridyl)‐1‐butanone, an internal standard for analysis of tobacco‐specific nitrosamine hemoglobin and DNA adducts

Jyh‐Ming ‐M Lin, Shantu Amin, Sharon E. Murphy, Jerome J. Solomon, Stephen S. Hecht

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

The synthesis of [3,3‐D2]4‐hydroxy‐1‐(3‐pyridyl)‐1‐butanone ([3,3‐D2]HPB), an internal standard for the analysis of hemoglobin and DNA adducts of tobacco‐specific nitrosamines, is reported. 3‐Pyridine carboxaldehyde was converted to 2‐(3‐pyridyl)‐1, 3‐dithiane. This was condensed with 2‐(2‐bromoethyl)‐1, 3‐dioxalane to yield 2‐[2‐(3‐pyridyl)‐1, 3‐dithiane]ethyl‐1, 3‐dioxalane. Selective hydroylsis of the aldehyde protecting group produced 4‐(1, 3‐dithian‐2‐yl)‐4‐(3‐pyridyl)‐butanal, which was then labeled with deuterium adjacent to the aldehyde carbonyl group. Reduction with LiAlH4 produced the corresponding alcohol. Removal of the dithianyl protecting group required protection of the alcohol as its t–butyldimethylsilyl ether. Treatment with AgNO3/N‐chlorosuccinimide in aqueous CH3CN produced [3,3‐D2]HPB.

Original languageEnglish (US)
Pages (from-to)285-292
Number of pages8
JournalJournal of Labelled Compounds and Radiopharmaceuticals
Volume33
Issue number4
DOIs
StatePublished - Apr 1993

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Nitrosamines
DNA Adducts
Aldehydes
Hemoglobins
Alcohols
Deuterium
Ether
butyraldehyde
lithium aluminum hydride

All Science Journal Classification (ASJC) codes

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

Cite this

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title = "Synthesis of [3,3‐D2]4‐hydroxy‐1‐(3‐pyridyl)‐1‐butanone, an internal standard for analysis of tobacco‐specific nitrosamine hemoglobin and DNA adducts",
abstract = "The synthesis of [3,3‐D2]4‐hydroxy‐1‐(3‐pyridyl)‐1‐butanone ([3,3‐D2]HPB), an internal standard for the analysis of hemoglobin and DNA adducts of tobacco‐specific nitrosamines, is reported. 3‐Pyridine carboxaldehyde was converted to 2‐(3‐pyridyl)‐1, 3‐dithiane. This was condensed with 2‐(2‐bromoethyl)‐1, 3‐dioxalane to yield 2‐[2‐(3‐pyridyl)‐1, 3‐dithiane]ethyl‐1, 3‐dioxalane. Selective hydroylsis of the aldehyde protecting group produced 4‐(1, 3‐dithian‐2‐yl)‐4‐(3‐pyridyl)‐butanal, which was then labeled with deuterium adjacent to the aldehyde carbonyl group. Reduction with LiAlH4 produced the corresponding alcohol. Removal of the dithianyl protecting group required protection of the alcohol as its t–butyldimethylsilyl ether. Treatment with AgNO3/N‐chlorosuccinimide in aqueous CH3CN produced [3,3‐D2]HPB.",
author = "Lin, {Jyh‐Ming ‐M} and Shantu Amin and Murphy, {Sharon E.} and Solomon, {Jerome J.} and Hecht, {Stephen S.}",
year = "1993",
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T1 - Synthesis of [3,3‐D2]4‐hydroxy‐1‐(3‐pyridyl)‐1‐butanone, an internal standard for analysis of tobacco‐specific nitrosamine hemoglobin and DNA adducts

AU - Lin, Jyh‐Ming ‐M

AU - Amin, Shantu

AU - Murphy, Sharon E.

AU - Solomon, Jerome J.

AU - Hecht, Stephen S.

PY - 1993/4

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N2 - The synthesis of [3,3‐D2]4‐hydroxy‐1‐(3‐pyridyl)‐1‐butanone ([3,3‐D2]HPB), an internal standard for the analysis of hemoglobin and DNA adducts of tobacco‐specific nitrosamines, is reported. 3‐Pyridine carboxaldehyde was converted to 2‐(3‐pyridyl)‐1, 3‐dithiane. This was condensed with 2‐(2‐bromoethyl)‐1, 3‐dioxalane to yield 2‐[2‐(3‐pyridyl)‐1, 3‐dithiane]ethyl‐1, 3‐dioxalane. Selective hydroylsis of the aldehyde protecting group produced 4‐(1, 3‐dithian‐2‐yl)‐4‐(3‐pyridyl)‐butanal, which was then labeled with deuterium adjacent to the aldehyde carbonyl group. Reduction with LiAlH4 produced the corresponding alcohol. Removal of the dithianyl protecting group required protection of the alcohol as its t–butyldimethylsilyl ether. Treatment with AgNO3/N‐chlorosuccinimide in aqueous CH3CN produced [3,3‐D2]HPB.

AB - The synthesis of [3,3‐D2]4‐hydroxy‐1‐(3‐pyridyl)‐1‐butanone ([3,3‐D2]HPB), an internal standard for the analysis of hemoglobin and DNA adducts of tobacco‐specific nitrosamines, is reported. 3‐Pyridine carboxaldehyde was converted to 2‐(3‐pyridyl)‐1, 3‐dithiane. This was condensed with 2‐(2‐bromoethyl)‐1, 3‐dioxalane to yield 2‐[2‐(3‐pyridyl)‐1, 3‐dithiane]ethyl‐1, 3‐dioxalane. Selective hydroylsis of the aldehyde protecting group produced 4‐(1, 3‐dithian‐2‐yl)‐4‐(3‐pyridyl)‐butanal, which was then labeled with deuterium adjacent to the aldehyde carbonyl group. Reduction with LiAlH4 produced the corresponding alcohol. Removal of the dithianyl protecting group required protection of the alcohol as its t–butyldimethylsilyl ether. Treatment with AgNO3/N‐chlorosuccinimide in aqueous CH3CN produced [3,3‐D2]HPB.

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