Alkynylamino-nucleotides
First Claim
Patent Images
1. An alkynylamino-nucleotide having the structure:
-
space="preserve" listing-type="equation">Nuc--C.tbd.C--R.sub.1 --NR.sub.2 R.sub.3whereinR1 is a diradical moiety of 1-20 atoms,R2 and R3 are, independently, H, C1 -C4 alkyl or a protecting group, and Nuc is R4 -Het having the structure ##STR16## Z is H or NH2, and R4 is ##STR17## wherein R5 is H, PO3 H2, P2 O6 H3, P3 O9 H4 or salts thereof, and(i) when R7 ═
R8 ═
H, then R6 ═
H, OH, F, N3 or NH2 ;
or(ii) when R7 ═
H and R8 ═
OH, then R6 ═
H or OH;
or(iii) when R7 ═
OH and R8 ═
H, then R6 ═
OH.
3 Assignments
0 Petitions
Accused Products
Abstract
Alkynylamino-nucleotides and labeled alkynylamino-nucleotides useful, for example, as chain terminating substrates for DNA sequencing are provided along with several key intermediates and processes for their preparation.
445 Citations
12 Claims
-
1. An alkynylamino-nucleotide having the structure:
-
space="preserve" listing-type="equation">Nuc--C.tbd.C--R.sub.1 --NR.sub.2 R.sub.3wherein R1 is a diradical moiety of 1-20 atoms, R2 and R3 are, independently, H, C1 -C4 alkyl or a protecting group, and Nuc is R4 -Het having the structure ##STR16## Z is H or NH2, and R4 is ##STR17## wherein R5 is H, PO3 H2, P2 O6 H3, P3 O9 H4 or salts thereof, and (i) when R7 ═
R8 ═
H, then R6 ═
H, OH, F, N3 or NH2 ;
or(ii) when R7 ═
H and R8 ═
OH, then R6 ═
H or OH;
or(iii) when R7 ═
OH and R8 ═
H, then R6 ═
OH. - View Dependent Claims (2, 3, 4, 5)
-
-
6. A labeled alkynylamino-nucleotide having the structure:
-
space="preserve" listing-type="equation">Nuc--C.tbd.C--R.sub.1 --NR.sub.2 R.sub.3wherein R1 is a diradical moiety of 1-20 atoms. R2 is H, C1 -C4 alkyl or a protecting group, and Nuc is R4 -Het having the structure ##STR18## Z is H or NH2, and R4 is ##STR19## wherein R5 is H, PO3 H2, P2 O6 H3, P3 O9 H4 or (i) when R7 ═
R8 ═
H, then R6 ═
H, OH, R, N3 or NH2 ;
or(ii) when R7 ═
H and R8 ═
OH, then R6 ═
H or OH;
or(iii) when R7 ═
OH and R8 ═
H, then R6 ═
OH,and RR3 is a reporter group. - View Dependent Claims (7)
-
-
8. A process for preparing 2-thioalkoxy-6-alkoxy-7-iodo-7-deazapurines wherein 2-thioalkoxy-7-deazapurines are reacted with N-iodosuccinimide for the regioselective introduction of iodine at the 7-position and obtaining the 7-iodo regioisomer.
-
9. A process of preparing 7-(3-amino-1-propynyl)2'"'"',3'"'"'-dideoxyguanosine 5'"'"'-triphosphate comprising the steps of:
-
(A) reacting 6-methoxy-2-methylthio-7-deazapurine with 1-chloro-2-deoxy-3,5-di-O-p-toluoyl-α
-D-ribofuranose in presence of sodium hydride;(B) hydrolyzing the ester product 9 of step (A) under basic condition to diol 10; (C) protecting the 5-OH position in diol 10 with a trityl group; (D) removing the 3-OH group by reducing an intermediate thionocarbonate with a tin hydride reducing agent; (E) treating the dideoxydeazapurine 12 resulting from step (D) with N-iodosuccinimide to form the 7-iodo derivative 13; (F) reacting compound 13 with sodium thiocresolate in hexamethylphosphoramide to form the 7-deazapurin-6-one 14; (G) treating compound 14 successively with meta-chloroperoxybenzoic acid and ammonia to obtain the 7-deazaguanosine 15; (H) coupling N-propargyltrifluoroacetamide to the deprotected 7-iodo compound 16 to obtain 7-(3-trifluoroacetamido-1-propynyl)-2'"'"',3'"'"'-dideoxy-7-deazaguanosine; and (I) reacting the product of step (H) sequentially with phosphorous oxychloride and pyrophosphate to convert it to the 5'"'"'-triphosphate followed by deprotection.
-
-
10. A process for preparing 6-chloro-7-iodo-7-deazapurines wherein 6-chloro-7-deazapurines are reacted with iodine monochloride for the regioselective introduction of iodine at the 7-position and obtaining the 7-iodo regioisomer.
-
11. An improved method for preparing alkynylaminonucleotides by coupling iodo-nucleotides having an iodine atom attached to a carbon atom within the heterocyclic base with terminal alkynyl amines using a bis(triphenylphosphine)palladium dichloride/cuprous iodide catalyst, the improvement comprising the use of a tetrakis(triphenylphosphine)palladium(O)/cuprous iodide catalyst.
-
12. 7-Iodo-nucleotides having the structure:
- ##STR20## Z is H or NH2, and R4 is ##STR21## wherein R5 is H, PO3 H2, P2 O6 H3, P3 O9 H4 or salts thereof, and
(i) when R7 ═
R8 ═
H, then R6 ═
H, OH, R, N3 or NH2 ;
or(ii) when R7 ═
H and R8 ═
OH, then R6 ═
H or OH;
or(iii) when R.sub. ═
OH and R8 ═
H, then R6 ═
OH.
- ##STR20## Z is H or NH2, and R4 is ##STR21## wherein R5 is H, PO3 H2, P2 O6 H3, P3 O9 H4 or salts thereof, and
Specification