The present invention relates to a process for in situ the preparation of mixtures of chelating agents by catalyzed reactions of diethanolamine derivatives with maleic acid and then with 2-halocarboxylic acid, to mixtures of chelating agents and methods using such chelating agents.

The disclosure features novel lipids and compositions involving the same. Nanoparticle compositions include a novel lipid as well as additional lipids such as phospholipids, structural lipids, and PEG lipids. Nanoparticle compositions further including therapeutic and/or prophylactics such as RNA are useful in the delivery of therapeutic and/or prophylactics to mammalian cells or organs to, for example, regulate polypeptide, protein, or gene expression.

The disclosure features novel lipids and compositions involving the same. Nanoparticle compositions include a novel lipid as well as additional lipids such as phospholipids, structural lipids, and PEG lipids. Nanoparticle compositions further including therapeutic and/or prophylactics such as RNA are useful in the delivery of therapeutic and/or prophylactics to mammalian cells or organs to, for example, regulate polypeptide, protein, or gene expression.

The present invention provides an oxa-spirodiphosphine ligand having a structure of general Formula (I) below:

##STR00001##

wherein in general Formula (I), R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are the same, and are alkyl, alkoxy, aryl, aryloxy, or hydrogen, in which R.sup.1, R.sup.2, R.sup.3 and R.sup.4 may or may not form a ring, any two of them may form a ring, or a polycyclic ring may be formed between two pairs of them; R.sup.5 and R.sup.6 is alkyl, aryl, or hydrogen; and R.sup.7 and R.sup.8 is alkyl, benzyl, or aryl. The present invention also provides a method for asymmetric hydrogenation of α,β-unsaturated carboxylic acids. A complex of the oxa-spirodiphosphine ligand with ruthenium shows excellent activity and enantioselectivity in the asymmetric hydrogenation of various α,β-unsaturated carboxylic acids, with which a chiral carboxylic acid product can be obtained with an enantioselectivity up to 99%.

The present invention provides an oxa-spirodiphosphine ligand having a structure of general Formula (I) below:

##STR00001##

wherein in general Formula (I), R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are the same, and are alkyl, alkoxy, aryl, aryloxy, or hydrogen, in which R.sup.1, R.sup.2, R.sup.3 and R.sup.4 may or may not form a ring, any two of them may form a ring, or a polycyclic ring may be formed between two pairs of them; R.sup.5 and R.sup.6 is alkyl, aryl, or hydrogen; and R.sup.7 and R.sup.8 is alkyl, benzyl, or aryl. The present invention also provides a method for asymmetric hydrogenation of α,β-unsaturated carboxylic acids. A complex of the oxa-spirodiphosphine ligand with ruthenium shows excellent activity and enantioselectivity in the asymmetric hydrogenation of various α,β-unsaturated carboxylic acids, with which a chiral carboxylic acid product can be obtained with an enantioselectivity up to 99%.

The present disclosure is directed synthetic methods for the preparation of 4-valyloxybutyric acid. The synthetic methods described herein employ a diverse array of protecting group strategies and reaction conditions. Additionally, the present disclosure is directed to compounds useful as synthetic intermediates in the preparation of 4-valyloxybutyric acid.

The present disclosure is directed synthetic methods for the preparation of 4-valyloxybutyric acid. The synthetic methods described herein employ a diverse array of protecting group strategies and reaction conditions. Additionally, the present disclosure is directed to compounds useful as synthetic intermediates in the preparation of 4-valyloxybutyric acid.

The present disclosure is directed synthetic methods for the preparation of 4-valyloxybutyric acid. The synthetic methods described herein employ a diverse array of protecting group strategies and reaction conditions. Additionally, the present disclosure is directed to compounds useful as synthetic intermediates in the preparation of 4-valyloxybutyric acid.

A method for site-selective deuteration of amino acids using a protein system having an aminotransferase (e.g., DsaD) and/or a small partner protein (e.g., DsaE). A non-deuterated amino acid is contacted with deuterium and an aminotransferase or a combination of an aminotransferase and a partner protein, to yield a Cα-deuterated or a Cα- and Cβ-deuterated amino acid. Cβ-deuterated amino acids can be accessed by contacting a Cα- and Cβ-deuterated amino acid with non-deuterium hydrogen and an aminotransferase to wash out the deuterium at the Ca carbon atom by the non-deuterium hydrogen.

A method for site-selective deuteration of amino acids using a protein system having an aminotransferase (e.g., DsaD) and/or a small partner protein (e.g., DsaE). A non-deuterated amino acid is contacted with deuterium and an aminotransferase or a combination of an aminotransferase and a partner protein, to yield a Cα-deuterated or a Cα- and Cβ-deuterated amino acid. Cβ-deuterated amino acids can be accessed by contacting a Cα- and Cβ-deuterated amino acid with non-deuterium hydrogen and an aminotransferase to wash out the deuterium at the Ca carbon atom by the non-deuterium hydrogen.