Diastereoisomers of formaldehyde derivatives of tetrahydrofolic acid and tetrahydroaminopterin

Susan Band Horwitz, G. Kwok, L. Wilson, R. L. Kisliuk

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Previous work on the diethylaminoethylcellulose chromatography of CH2O derivatives of tetrahydrofolic acid leading to the isolation of diastereoisomers, designated as 5,10-methylene derivatives, was repeated using formaldehyde-14C. The isolated material contained 0.7-0.8 mole of formaldehyde/mole of tetrahydrofolate rather than 1 required for the 5,10-methylene structure. This finding was verified by chemical determination of CH2O on the isolated material. Comparable experiments with CH2O derivatives of tetrahydroaminopterin yielded 0.7 mole of CH2O/mole of tetrahydropteridine. These results suggest that the compounds designated as diastereoisomers of 5,10-methylenetetrahydrofolate are actually complexes which contain 4 molecules of tetrahydropteridine and 3 molecules of formaldehyde. The diastereoisomer complex of CH2O and tetrahydroaminopterin corresponding chromatographically to the diastereoisomer complex of CH2O and tetrahydrofolate, which is biologically active, was more inhibitory to the growth of Pediococcus cerevisiae and Streptococcus faecalis than that corresponding to the biologically inactive diastereoisomer complex of formaldehyde and tetrahydrofolate. When the diastereoisomer complexes of tetrahydroaminopterin were combined a synergistic effect on growth inhibition was obtained. Each diastereoisomer complex inhibited mouse tumor dihydrofolate reductase to the same extent. Neither diastereoisomer complex showed significant inhibition of Escherichia coli thymidylate synthetase.

Original languageEnglish (US)
Pages (from-to)49-51
Number of pages3
JournalJournal of Medicinal Chemistry
Volume12
Issue number1
StatePublished - 1968
Externally publishedYes

Fingerprint

Formaldehyde
Derivatives
Pediococcus
Thymidylate Synthase
Tetrahydrofolate Dehydrogenase
Molecules
Enterococcus faecalis
Growth
Chromatography
Escherichia coli
Tumors
5,6,7,8-tetrahydrofolic acid
Neoplasms
Experiments
5,6,7,8-tetrahydropteridine

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Diastereoisomers of formaldehyde derivatives of tetrahydrofolic acid and tetrahydroaminopterin. / Band Horwitz, Susan; Kwok, G.; Wilson, L.; Kisliuk, R. L.

In: Journal of Medicinal Chemistry, Vol. 12, No. 1, 1968, p. 49-51.

Research output: Contribution to journalArticle

@article{341662fe232d450b83f25eb4262a2410,
title = "Diastereoisomers of formaldehyde derivatives of tetrahydrofolic acid and tetrahydroaminopterin",
abstract = "Previous work on the diethylaminoethylcellulose chromatography of CH2O derivatives of tetrahydrofolic acid leading to the isolation of diastereoisomers, designated as 5,10-methylene derivatives, was repeated using formaldehyde-14C. The isolated material contained 0.7-0.8 mole of formaldehyde/mole of tetrahydrofolate rather than 1 required for the 5,10-methylene structure. This finding was verified by chemical determination of CH2O on the isolated material. Comparable experiments with CH2O derivatives of tetrahydroaminopterin yielded 0.7 mole of CH2O/mole of tetrahydropteridine. These results suggest that the compounds designated as diastereoisomers of 5,10-methylenetetrahydrofolate are actually complexes which contain 4 molecules of tetrahydropteridine and 3 molecules of formaldehyde. The diastereoisomer complex of CH2O and tetrahydroaminopterin corresponding chromatographically to the diastereoisomer complex of CH2O and tetrahydrofolate, which is biologically active, was more inhibitory to the growth of Pediococcus cerevisiae and Streptococcus faecalis than that corresponding to the biologically inactive diastereoisomer complex of formaldehyde and tetrahydrofolate. When the diastereoisomer complexes of tetrahydroaminopterin were combined a synergistic effect on growth inhibition was obtained. Each diastereoisomer complex inhibited mouse tumor dihydrofolate reductase to the same extent. Neither diastereoisomer complex showed significant inhibition of Escherichia coli thymidylate synthetase.",
author = "{Band Horwitz}, Susan and G. Kwok and L. Wilson and Kisliuk, {R. L.}",
year = "1968",
language = "English (US)",
volume = "12",
pages = "49--51",
journal = "Journal of Medicinal Chemistry",
issn = "0022-2623",
publisher = "American Chemical Society",
number = "1",

}

TY - JOUR

T1 - Diastereoisomers of formaldehyde derivatives of tetrahydrofolic acid and tetrahydroaminopterin

AU - Band Horwitz, Susan

AU - Kwok, G.

AU - Wilson, L.

AU - Kisliuk, R. L.

PY - 1968

Y1 - 1968

N2 - Previous work on the diethylaminoethylcellulose chromatography of CH2O derivatives of tetrahydrofolic acid leading to the isolation of diastereoisomers, designated as 5,10-methylene derivatives, was repeated using formaldehyde-14C. The isolated material contained 0.7-0.8 mole of formaldehyde/mole of tetrahydrofolate rather than 1 required for the 5,10-methylene structure. This finding was verified by chemical determination of CH2O on the isolated material. Comparable experiments with CH2O derivatives of tetrahydroaminopterin yielded 0.7 mole of CH2O/mole of tetrahydropteridine. These results suggest that the compounds designated as diastereoisomers of 5,10-methylenetetrahydrofolate are actually complexes which contain 4 molecules of tetrahydropteridine and 3 molecules of formaldehyde. The diastereoisomer complex of CH2O and tetrahydroaminopterin corresponding chromatographically to the diastereoisomer complex of CH2O and tetrahydrofolate, which is biologically active, was more inhibitory to the growth of Pediococcus cerevisiae and Streptococcus faecalis than that corresponding to the biologically inactive diastereoisomer complex of formaldehyde and tetrahydrofolate. When the diastereoisomer complexes of tetrahydroaminopterin were combined a synergistic effect on growth inhibition was obtained. Each diastereoisomer complex inhibited mouse tumor dihydrofolate reductase to the same extent. Neither diastereoisomer complex showed significant inhibition of Escherichia coli thymidylate synthetase.

AB - Previous work on the diethylaminoethylcellulose chromatography of CH2O derivatives of tetrahydrofolic acid leading to the isolation of diastereoisomers, designated as 5,10-methylene derivatives, was repeated using formaldehyde-14C. The isolated material contained 0.7-0.8 mole of formaldehyde/mole of tetrahydrofolate rather than 1 required for the 5,10-methylene structure. This finding was verified by chemical determination of CH2O on the isolated material. Comparable experiments with CH2O derivatives of tetrahydroaminopterin yielded 0.7 mole of CH2O/mole of tetrahydropteridine. These results suggest that the compounds designated as diastereoisomers of 5,10-methylenetetrahydrofolate are actually complexes which contain 4 molecules of tetrahydropteridine and 3 molecules of formaldehyde. The diastereoisomer complex of CH2O and tetrahydroaminopterin corresponding chromatographically to the diastereoisomer complex of CH2O and tetrahydrofolate, which is biologically active, was more inhibitory to the growth of Pediococcus cerevisiae and Streptococcus faecalis than that corresponding to the biologically inactive diastereoisomer complex of formaldehyde and tetrahydrofolate. When the diastereoisomer complexes of tetrahydroaminopterin were combined a synergistic effect on growth inhibition was obtained. Each diastereoisomer complex inhibited mouse tumor dihydrofolate reductase to the same extent. Neither diastereoisomer complex showed significant inhibition of Escherichia coli thymidylate synthetase.

UR - http://www.scopus.com/inward/record.url?scp=0014440883&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0014440883&partnerID=8YFLogxK

M3 - Article

C2 - 4883936

AN - SCOPUS:0014440883

VL - 12

SP - 49

EP - 51

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

SN - 0022-2623

IS - 1

ER -