Synthesis of a putative ddhCTP metabolite ddhC-homocysteine

James M. Wood; Joshua N. Buckler; Steven C. Almo; Gary B. Evans; Tyler L. Grove; Lawrence D. Harris

doi:10.1016/j.tetlet.2023.154423

Synthesis of a putative ddhCTP metabolite ddhC-homocysteine

James M. Wood, Joshua N. Buckler, Steven C. Almo, Gary B. Evans, Tyler L. Grove, Lawrence D. Harris

Biochemistry

Research output: Contribution to journal › Article › peer-review

Abstract

A concise synthesis of 3′,4′-didehydro-3′,5′-dideoxycytidine-5′-S-L-homocysteine (ddhC-homocys) is reported. The synthesis confirms the identity of a metabolite previously observed in the urine of malaria-infected mice, which is likely derived from the endogenous antiviral nucleotide analogue 3′,4′-didehydro-3′-deoxycytidine triphosphate (ddhCTP). Additionally, a simple strategy for incorporation of heavy-atom labelling into the ddhC scaffold is described, which will enable investigation of the metabolic fate of ddhCTP in cells.

Original language	English (US)
Article number	154423
Journal	Tetrahedron Letters
Volume	119
DOIs	https://doi.org/10.1016/j.tetlet.2023.154423
State	Published - Apr 12 2023

Keywords

Metabolites
Nucleoside synthesis
ddh-homocys
ddhCTP

ASJC Scopus subject areas

Biochemistry
Drug Discovery
Organic Chemistry

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.tetlet.2023.154423

Cite this

@article{e5df9df261614dd1bc371d6c966666f9,

title = "Synthesis of a putative ddhCTP metabolite ddhC-homocysteine",

abstract = "A concise synthesis of 3′,4′-didehydro-3′,5′-dideoxycytidine-5′-S-L-homocysteine (ddhC-homocys) is reported. The synthesis confirms the identity of a metabolite previously observed in the urine of malaria-infected mice, which is likely derived from the endogenous antiviral nucleotide analogue 3′,4′-didehydro-3′-deoxycytidine triphosphate (ddhCTP). Additionally, a simple strategy for incorporation of heavy-atom labelling into the ddhC scaffold is described, which will enable investigation of the metabolic fate of ddhCTP in cells.",

keywords = "Metabolites, Nucleoside synthesis, ddh-homocys, ddhCTP",

author = "Wood, {James M.} and Buckler, {Joshua N.} and Almo, {Steven C.} and Evans, {Gary B.} and Grove, {Tyler L.} and Harris, {Lawrence D.}",

note = "Publisher Copyright: {\textcopyright} 2023 Elsevier Ltd",

year = "2023",

month = apr,

day = "12",

doi = "10.1016/j.tetlet.2023.154423",

language = "English (US)",

volume = "119",

journal = "Tetrahedron Letters",

issn = "0040-4039",

publisher = "Elsevier Limited",

}

TY - JOUR

T1 - Synthesis of a putative ddhCTP metabolite ddhC-homocysteine

AU - Wood, James M.

AU - Buckler, Joshua N.

AU - Almo, Steven C.

AU - Evans, Gary B.

AU - Grove, Tyler L.

AU - Harris, Lawrence D.

PY - 2023/4/12

Y1 - 2023/4/12

N2 - A concise synthesis of 3′,4′-didehydro-3′,5′-dideoxycytidine-5′-S-L-homocysteine (ddhC-homocys) is reported. The synthesis confirms the identity of a metabolite previously observed in the urine of malaria-infected mice, which is likely derived from the endogenous antiviral nucleotide analogue 3′,4′-didehydro-3′-deoxycytidine triphosphate (ddhCTP). Additionally, a simple strategy for incorporation of heavy-atom labelling into the ddhC scaffold is described, which will enable investigation of the metabolic fate of ddhCTP in cells.

AB - A concise synthesis of 3′,4′-didehydro-3′,5′-dideoxycytidine-5′-S-L-homocysteine (ddhC-homocys) is reported. The synthesis confirms the identity of a metabolite previously observed in the urine of malaria-infected mice, which is likely derived from the endogenous antiviral nucleotide analogue 3′,4′-didehydro-3′-deoxycytidine triphosphate (ddhCTP). Additionally, a simple strategy for incorporation of heavy-atom labelling into the ddhC scaffold is described, which will enable investigation of the metabolic fate of ddhCTP in cells.

KW - Metabolites

KW - Nucleoside synthesis

KW - ddh-homocys

KW - ddhCTP

UR - http://www.scopus.com/inward/record.url?scp=85149737521&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85149737521&partnerID=8YFLogxK

U2 - 10.1016/j.tetlet.2023.154423

DO - 10.1016/j.tetlet.2023.154423

M3 - Article

AN - SCOPUS:85149737521

SN - 0040-4039

VL - 119

JO - Tetrahedron Letters

JF - Tetrahedron Letters

M1 - 154423

ER -

Synthesis of a putative ddhCTP metabolite ddhC-homocysteine

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this