Compositions and methods for phosphoramidite and oligonucleotide synthesis
AssigneeWave Life Sciences Ltd.
InventorsDavid Charles Donnell Butler, Pachamuthu Kandasamy, Subramanian Marappan, Ik-Hyeon Paik, Jayakanthan Kumarasamy, Gopal Reddy Bommineni
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Abstract
The present disclosure, among other things, provides technologies for oligonucleotide synthesis. In some embodiments, the present disclosure provides phosphoramidites and methods for synthesis thereof. In some embodiments, provided methods provides higher yields and/or purities. In some embodiments, provided methods remove byproducts without contact with an aqueous solution.
Claims21
-33. (canceled)
A method for preparing a phosphoramidite, comprising contacting a nucleoside with a silylating reagent in a solution and contacting the solution with a phosphorochloridite, wherein:
- the nucleoside has the structure of formula I-a or a salt thereof:
- the phosphorochloridite has the structure of formula I-b or a salt thereof;
- the phosphoramidite has the structure of formula I:
- BA is
- wherein R is hydrogen or optionally substituted C1-6 aliphatic;
- SU is
- R5s is R′ or —OR′;
- R2s is —H, —F, —CN, —N3, —NO, —NO2, —O—(C1-10 alkyl), or —O-(optionally substituted C1-6 alkylene)-OR′, or R2s is L connecting C2 with C1, C2, C3, C4 or C5, wherein L is —O—CH2— wherein the —CH2— is optionally substituted;
- each R′ is independently —R, —C(O)R, —CO2R, or —SO2R, or:
- two or more R′ are taken together with their intervening atoms to form an optionally substituted monocyclic, bicyclic or polycyclic, saturated, partially unsaturated, or aryl 3-30 membered ring having, in addition to the intervening atoms, 0-10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus and silicon;
- and
- each R is independently hydrogen, or an optionally substituted group selected from C1-30 aliphatic, C1-30 heteroaliphatic having 1-10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus and silicon, C6-30 aryl, a 5-30 membered heteroaryl ring having 1-10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus and silicon, and a 3-30 membered heterocyclic ring having 1-10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus and silicon.
Dependencies are inferred from the claim text.