Provided herein are ionizable lipids represented by the Formula (I): or a pharmaceutically acceptable salt thereof, wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.1′, R.sup.2′, R.sup.3′, R.sup.4′, R.sup.5′, R.sup.6′, m, and n are as defined herein. Also provided herein are lipid nanoparticle (LNP) compositions comprising an ionizable lipid of the invention and a capsid-free, non-viral vector (e.g., ceDNA). These LNPs can be used to deliver a capsid-free, non-viral DNA vector to a target site of interest (e.g., cell, tissue, organ, and the like).

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Compounds having cytotoxic and/or anti-mitotic activity are disclosed. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed. Also disclosed are compositions having the structure: (T)-(L)-(D), wherein (T) is a targeting moiety, (L) is an optional linker, and (D) is a compound having cytotoxic and/or anti-mitotic activity.

Described herein is a precursor compound of formula (I) releasing 2-acetyl-1-pyrroline and a method to release 2-acetyl-1-pyrroline from the precursor compound of formula (I)

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in the form of any one of its stereoisomers, tautomers, salts or as a mixture thereof, where R.sup.1 represents a hydrogen atom or a C.sub.1 to C.sub.10 hydrocarbon group optionally including one to three heteroatoms; X represents an amino acid, a peptide or a OR.sup.2 wherein R.sup.2 represents a hydrogen atom or a C.sub.1 to C.sub.20 hydrocarbon group optionally including one to three heteroatoms and n is 0 when the dotted line represents a single bond or n is 1 when the dotted line represents no bond.

Described herein is a precursor compound of formula (I) releasing 2-acetyl-1-pyrroline and a method to release 2-acetyl-1-pyrroline from the precursor compound of formula (I)

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in the form of any one of its stereoisomers, tautomers, salts or as a mixture thereof, where R.sup.1 represents a hydrogen atom or a C.sub.1 to C.sub.10 hydrocarbon group optionally including one to three heteroatoms; X represents an amino acid, a peptide or a OR.sup.2 wherein R.sup.2 represents a hydrogen atom or a C.sub.1 to C.sub.20 hydrocarbon group optionally including one to three heteroatoms and n is 0 when the dotted line represents a single bond or n is 1 when the dotted line represents no bond.

The disclosure provides processes for synthesizing Compound I, and pharmaceutically acceptable salts thereof. ##STR00001##

The disclosure provides processes for synthesizing Compound I, and pharmaceutically acceptable salts thereof. ##STR00001##

The present disclosure, among other things, provides technologies for synthesis, including reagents and methods for stereoselective synthesis. In some embodiments, the present disclosure provides compounds useful as chiral auxiliaries. In some embodiments, the present disclosure provides reagents and methods for oligonucleotide synthesis. In some embodiments, the present disclosure provides reagents and methods for chirally controlled preparation of oligonucleotides. In some embodiments, technologies of the present disclosure are particularly useful for constructing challenging internucleotidic linkages, providing high yields and stereoselectivity.

The present disclosure, among other things, provides technologies for synthesis, including reagents and methods for stereoselective synthesis. In some embodiments, the present disclosure provides compounds useful as chiral auxiliaries. In some embodiments, the present disclosure provides reagents and methods for oligonucleotide synthesis. In some embodiments, the present disclosure provides reagents and methods for chirally controlled preparation of oligonucleotides. In some embodiments, technologies of the present disclosure are particularly useful for constructing challenging internucleotidic linkages, providing high yields and stereoselectivity.

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Compounds of formula (I), formula (II), or formula (III) and their use with a neurological or psychiatric disorder, mediated by Kv11.1-3.1 containing potassium channels, including schizophrenia, are disclosed.

The invention provides heterocyclic compounds with quaternary centers and methods of preparing compounds. Methods include the method for the preparation of a compound of Formula (II):

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comprising treating a compound of Formula (I):

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with a transition metal catalyst and under alkylation conditions as valence and stability permit.