Patent ID: 6084082
Filing Date: 2000-07-04
Classification: C07D,C07F

Abstract:
A method for preparing a .beta.-lactamtide comprising:a) providing a .beta.-lactam having a functional group, a protected hydroxyl group, and a hydroxyl group covalently bonded thereto;said functional group is a nucleobase, furthermore, said functional group can be optionally substituted with one or more additional functional groups selected from hydrogen, hydroxyl, alkyl, substituted alkyl, alkaryl or aralkyl, F, Cl, Br, CN, CF.sub.3, OCF.sub.3, OCN, O-alkyl, S-alkyl, N-alkyl, O-alkenyl, S-alkenyl, N-alkenyl, SOCH.sub.3, SO.sub.2 CH.sub.3, ONO.sub.2, NO.sub.2, N.sub.3, NH.sub.2, heterocycloalkyl, heterocycloalkaryl, aminoalkylamino, polyalkylamino or substituted silyl, an RNA cleaving group, or a reporter ligand;b) attaching said .beta.-lactam to a solid support via said hydroxyl group;c) treating said protected hydroxyl group with a deprotecting reagent to give a free hydroxyl group;d) reacting said free hydroxyl group with a .beta.-lactamtide having an activated phosphite group, a functional group as defined above, and a protected hydroxyl group thereon to form a phosphite triester;e) oxidizing said phosphite triester to a phosphate triester or to a phosphorothioate;wherein said functional group attached to said .beta.-lactam and said functional group attached to said .beta.-lactamtide are each optionally attached using a tether of formula (CR.sub.6 R.sub.7).sub.x where R.sub.6 and R.sub.7 are independently selected from the group consisting of hydrogen. (C.sub.2 -C.sub.6)alkyl aryl, aralkyl, heteroaryl hydroxy, (C.sub.1 -C.sub.6)alkoxvy (C.sub.1 -C.sub.6)alkylthio, NR.sub.3 R.sub.4 and SR.sub.5, where each of R.sub.3 and R.sub.4 is independently selected from the group consisting of hydrogen, (C.sub.1 -C.sub.4)alkyl, alkoxy, or alkylthio-substituted (C.sub.1 -C.sub.4) alkyl, alkoxy, alkylthio and amino; and R.sub.5 is hydrogen, (C.sub.1 -C.sub.6)alkyl hydroxy-, alkoxy-, or alkylthio- substituted (C.sub.1 -C.sub.6)alkyl, or R.sub.6 and R.sub.7 taken together complete an alicyclic system, and where .sub.x is an integer from 1 to 10, and can be 0 only when said functional group is not hydrogen or hydroxyl.