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Synthesis of 3′‐Thioamido‐Modified 3′‐Deoxythymidine 5′‐Triphosphates by Regioselective Thionation and Their Use as Chain Terminators in DNA Sequencing
Author(s) -
Wojczewski Christian,
Schwarzer Karin,
Engels Joachim W.
Publication year - 2000
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/1522-2675(20000607)83:6<1268::aid-hlca1268>3.0.co;2-s
Subject(s) - chemistry , reagent , thioamide , thymidine , regioselectivity , stereochemistry , pyridine , dna , combinatorial chemistry , organic chemistry , biochemistry , catalysis
The thioamide derivatives 3′‐deoxy‐5′‐ O ‐(4,4′‐dimethoxytrityl)‐3′‐[(2‐methyl‐1‐thioxopropyl)amino]thymidine ( 4a ) and 3′‐deoxy‐5′‐ O ‐(4,4′‐dimethoxytrityl)‐3′‐{{6‐{[(9 H ‐(fluoren‐9‐ylmethoxy)carbonyl]amino}‐1‐thioxohexyl}amino}thymidine ( 4b ) were synthesized by regioselective thionation of the corresponding amides 3a and 3b with 2,4‐bis(4‐methoxyphenyl)‐1,3,2,4‐dithiadiphosphetane 2,4‐disulfide ( Lawesson 's reagent). The addition of exact amounts of pyridine to the reaction mixture proved to be essential for an efficient transformation. The thioamides were converted into the corresponding 5′‐triphosphates 6a and 6b . Compound 6a was chosen for DNA sequencing experiments, and 6b was further labelled with fluorescein (→ 8 ).