| 主权项 |
1. A method of preparing a compound of the formulacomprising
(i) attaching a conjugation component of the formulawherein R2 is R2a or Rap,
to a solid supportto form a compound of the formula (ii) when R2 is R2ap, convertingand
(iii) contactingwith a conjugation component of the formulawherein R3 is R3a, R3ap, hydrogen, a detectable label or an oligo;
to formwherein:is a solid support material;are independently an oligo;
R1a and R1b are complementary conjugation functionalities and L1 is conjugate linker, and R1a, R1b, and L1 are (a) R1a is azido, R1b is —C≡C—R23,or
(b) R1a is —NHR23, R1b is carboxy, and L1 is —NR23C(═O)—, or (c) R1a is carboxy, R1b is —NHR23, and L1 is —C(═O)NR23—, or (d) R1a is —NHR23, R1b is halo, and L1 is —NR23—, or (e) R1a is —O—P(═O)(OH)(X), R1b is hydroxy, and L1 is —O—P(═O)(OH)—O—, or (f) R1a is —O—P(═O)(OH)(X), R1b is —NHR23, and L1 is —O—P(═O)(OH)—NR23—, or (g) R1a is —O—P(═O)(OH)(X), R1b is thio, and L1 is —O—P(═O)(OH)—S—, or (h) R1a is halo, R1b is thio, and L1 is —S—, or (i) R1a isR1b is thio, and L1 isor
(j) R1a is —C≡C—R23, R1b is azido, and L1 isor
(k) R1a is halo, R1b is —NHR23, and L1 is —NR23—, or (l) R1a is hydroxy, R1b is —O—P(═O)(OH)(X), and L1 is —O—P(═O)(OH)—O—, or (m) R1a is —NHR23, R1b is —O—P(═O)(OH)(X), and L1 is —NR23—P(═O)(OH)—O—, or (n) R1a is thio, R1b is —O—P(═O)(OH)(X), and L1 is —S—P(═O)(OH)—O—, or (o) R1a is —O—P(═O)(OH)SH, R1b is —X, and L1 is —O—P(═O)(OH)—S—, or (p) R1a is —X, R1b is —O—P(═O)(OH)SH, and L1 is —S—P(═O)(OH)—O—, or (q) R1a is —(CR25R2s)sC(═O)OR23, R1b is —NHR23, L1 is —(CR25R25)sC(═O)NR23—, or (r) R1a is —NHR23, R1b is —(CR25R25)sC(═O)OR23, L1 is —NR23C(═O)—(CR25R25), or (s) R1a is thio, R1b is halo, and L1 is —S—, or (t) R1a is thio, R1b isand L1 is (u) R1a is —SH, R1b is —O—P(═O)(OH)(O—(CH2)n—SH) and L1 is —S—S—(CH2)—O—P(OH)(═O)—O—; R2a and R2b are complementary conjugation functionalities and L2 is conjugate linker, and R2ap, R2a, R2b, and L2 are (a′) R2ap is halo, R2a is azido, R2b is —C≡C—R23, and L2 isor
(b′) R2ap is —NR23Pr, R2a is —NHR23, R2b is carboxy, and L2 is —NR23C(═O)—, or (c′) R2ap is carboxy ester, R2a is carboxy, R2b is —NHR23, and L2 is —C(═O)NR23—, or (d′) R2ap is —NR23Pr, R2a is —NHR23, R2b is halo, and L2 is —NR23—, or (e′) R2ap is —OH, phosphate or phosphate ester, R2a is —O—P(═O)(OH)(X), R2b is hydroxy, and L2 is —O—P(═O)(OH)—O—, or (f) R2ap is —OH, phosphate or phosphate ester, R2a is —O—P(═O)(OH)(X), R2b is —NHR23, and L2 is —O—P(═O)(OH)—NR23—, or (g′) R2ap is —OH, phosphate or phosphate ester, R2a is —O—P(═O)(OH)(X), R2b is thio, and L2 is —O—P(═O)(OH)—S—, or (h′) R2a is —X, R2b is thio, and L2 is —S—, or (i′) R2a isR2b is thio, and L2 isor
(j′) R2a is —C≡C—R23, R2b is azido, and L2 isor
(k′) R2a is halo, R2b is —NHR23, and L2 is —NR23—, or (l′) R2a is hydroxy, R2b is —O—P(═O)(OH)(X), and L2 is —O—P(═O)(OH)—O—, or (m′) R2a is —NHR23, R2b is —O—P(═O)(OH)(X), and L2 is —NR23—P(═O)(OH)—O—, or (n′) R2a is thio, R2b is —O—P(═O)(OH)(X), and L2 is —S—P(═O)(OH)—O—, or (o′) R2ap is —O—P(═O)(OH)SR24, R2a is —O—P(═O)(OH)SH, R2b is —X, and L2 is —O—P(═O)(OH)—S—, or (p′) R2a is —X, R2b is —O—P(═O)(OH)SH, and L2 is —S—P(═O)(OH)—O—, or (q′) R2a is —(CR25R25)sC(═O)OR23, R2b is —NHR23, L2 is —(CR25R25)C(═O)NR23—, or (r′) R1a is —NHR23, R2b is —(CR25R25)sC(═O)OR23, L2 is —NR23C(═O)—(CR25R25)s—, or (s′) R2a is thio, R2b is halo, and L2 is —S—, or (t′) R2a is thio, R2b isand L2 isor
(u′) R2a is —SH, R2b is —O—P(═O)(OH)(O—(CH2)n—SH) and L2 is —S—S—(CH2)n—O—P(OH)(═O)—O—; X is selected from chlorine, bromine, fluorine, tosylate, mesylate, triflate, or dimethoxy triflate, n is 1, 2, 3, 4, 5, or 6; R23 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, cycloalkynyl, substituted cycloalkynyl, heteroaryl, substituted heteroaryl, heterocyclic, and substituted heterocyclic; Pr is an amino protecting group; R24 is trityl or benzyl; R25 is hydrogen or C1-6 alkyl; n is 1, 2, 3, 4, 5, or 6; s is an integer of greater than 1; R3ap is selected from the group consisting of halo, —OH, —NR23Pr, —O—P(═O)(OH)SR24, carboxy ester, phosphate and phosphate ester; and R3a is selected from the group consisting of azido, —C≡C—R23, —NHR23, carboxy, halo, hydroxy, —C(═O)OR23, —O—P(═O)(OH)SH and —O—P(═O)(OH)Br; provided that R2 does not react with R1a or R1b, and R3 does not react with R2a or R2b; - - - - - represents the point of connection to the part of the solid support-bound conjugated molecule that is closer toand represents the point of connection to the part of the solid support-bound conjugated molecule that is further away from |
