An approach towards the synthesis of oligomers containing a N-2-hydroxyethyl-aminomethylphosphonate backbone: A novel PNA analogues

Tetrahedron Letters

Volumn 37, Issue 43, 1996, Pages 7857-7860

  Van Der Laan, Alexander C ^a   Strömberg, Roger ^b   Van Boom, Jacques H ^a   Kuyl Yeheskiely, Esther ^a   Efimov, Vladimir A ^c   Chakhmakhcheva, Oksana G ^c  

^a LEIDEN UNIVERSITY   (Netherlands)

^b KAROLINSKA INSTITUTE   (Sweden)

^c SHEMYAKIN OVCHINNIKOV INSTITUTE OF BIOORGANIC CHEMISTRY   (Russian Federation)

Author keywords

[No Author keywords available]

Indexed keywords

NUCLEOSIDE DERIVATIVE; OLIGONUCLEOTIDE;

ARTICLE; DRUG SYNTHESIS; REACTION ANALYSIS; TECHNIQUE;

EID: 0002912512     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/0040-4039(96)01750-9     Document Type: Article

References (16)

1. 1. a) Milligan, J.F.; Matteucci, M.D.; Martin, J.C. J. Med. Chem. 1993, 36, 1923-1937.
2. b) Hunziker, J.; Leumann, C. in "Modern Synthetic Methods 1995", Ernst, B.; Leumann, E. Eds., Verlag Helv. Chim. Acta, Basel, p. 331-417 and references cited therein.
3. 2. a) Nielsen, P.E.; Egholm, M.; Berg, R.H.; Buchardt, O. Science 1991, 254, 1497-1500.
4. b) Egholm, M.; Nielsen, P.E.; Buchardt, O.; Berg, R.H. J. Am. Chem. Soc. 1992, 114, 9677-9678.
5. 3. a) Bergmann, F.; Bannwarth, W.; Tam, S. Tetrahedron Lett. 1995, 36, 6823-6826.
6. b) Egholm, M.; Buchardt, O.; Nielsen, P.E.; Berg, R.H. J. Am. Chem. Soc. 1992, 114, 1895-1897.
7. 4. Szabo, T.; Kers, A.; Stawinski, J. Nucl. Acids Res. 1995, 23, 893-900.
8. 5. Efimov, V.A.; Buryakova, A.A.; Dubey, I.Y.; Polushin, N.N.; Chakhmakhcheva, O.G.; Ovchinnikov, Y.A. Nucl. Acids Res. 1986, 14, 6526-6540.
9. 6. Compound 2 was readily prepared by tritylation of commercially available N-(hydroxyethyl)phtalimide with DMT-Cl (1.1 eq) in pyridine and subsequent treatment of the tritylated product with hydrazine (2.0 eq) in 80% overall yield.
10. 7. De Lombaert, S.; Erion, M.D.; Tan, J.; Blachard, L.; El-Chehabi, L.; Ghai, R.D.; Sakane, Y.; Berry, C.; Trapani, A.I. J. Med. Chem. 1994, 37, 498-511.
11. 8. Meltzer, P.C.; Liang, A.Y.; Matasudaira, P. J. Org. Chem. 1995, 60, 4305-4308.
12. 3, MOPM), 96.4 (C-5), 119.7 (CH, Ph).
13. 2 (15 mL) and precipitated from diethyl ether (200 mL). The precipitate was collected by centrifugation and dried in vacuo to give 7a (or 7b).
14. 2O (95/5, v/v, 10 mL) for 30 min to give 1a (or 1b).
15. 12. The solid-support synthesis was carried out on a Pharmacia Gene Assembler using preloaded 5-O-DMT-dT-succinyl-CPG (loading 35 μmole/g, purchased from Millipore) as support.
16. 13. FPLC analysis was carried out on a Pharmacia mono-Q HR 5/5 column (anion exchange). Gradient elution was performed at 20°C by building up a gradient starting with buffer A (0.01 M NaOH, pH = 12) and applying buffer B (0.01 M NaOH, 1.2 M NaCl, pH = 12.0) at a flow rate of 2.0 mL/min.