It has been found that the membrane permeability of peptide compounds can be improved by making at least one of amino acids constituting the peptide compound be an amino acid having a side chain capable of forming an intramolecular hydrogen bond.

This invention provides illudin derivatives, intermediates, preparation methods, pharmaceutical compositions and uses thereof. Specific examples include novel synthetic routes to prepare illudin derivatives and an illudin derivative having a positive optical rotation, which has therapeutic value.

The field of new compounds and synthesis methods thereof are related, and particularly to a structure of a steric hindrance adjustable weak base light stabilizer and a preparation method and application thereof. According to the innovative light stabilizer, a steric hindrance thereof is adjusted by establishing substituent generating the steric hindrance around nitrogen atoms; moreover, an electronegativity of the nitrogen atom can be influenced by adjusting a distance of a polar group, so that an alkalinity or a nucleophilicity of the nitrogen atom is adjusted. A desired effect is obtained by adjusting a steric hindrance and a nucleophilic property or an alkalinity where the nitrogen atom is located, so that an application range of the innovative light stabilizer is widened, and the innovative light stabilizer is suitable for PC, polyester, PVC and other slightly acidic or certain electrophilic polymer materials to serve as a light stability protecting aid.

Novel lipids, compositions, and methods of using the novel lipids and compositions are disclosed. Three-component lipid nanoparticle compositions comprising the novel lipids or other types of lipids, and methods of using the three-component lipid nanoparticle compositions are disclosed. Three-component lipid nanoparticle compositions contain a steroidal or structural lipid-containing component, a PEGylated lipid-containing component, a cationic or ionizable lipid-containing component, and are free of phospholipids. Pharmaceutical formulations including the three-component lipid nanoparticle compositions and further including therapeutic and/or prophylactics such as mRNA are useful in the delivery of therapeutic and/or prophylactics to mammalian cells or organs.

Novel lipids, compositions, and methods of using the novel lipids and compositions are disclosed. Three-component lipid nanoparticle compositions comprising the novel lipids or other types of lipids, and methods of using the three-component lipid nanoparticle compositions are disclosed. Three-component lipid nanoparticle compositions contain a steroidal or structural lipid-containing component, a PEGylated lipid-containing component, a cationic or ionizable lipid-containing component, and are free of phospholipids. Pharmaceutical formulations including the three-component lipid nanoparticle compositions and further including therapeutic and/or prophylactics such as mRNA are useful in the delivery of therapeutic and/or prophylactics to mammalian cells or organs.

This invention provides illudin derivatives, intermediates, preparation methods, pharmaceutical compositions and uses thereof. Specific examples include novel synthetic routes to prepare illudin derivatives and an illudin derivative having a positive optical rotation, which has therapeutic value.

New regulator compounds for a novel polymerization process for vinyl monomers, which yields polymers with improved control over composition and nearly full to full conservation of architectural integrity up to high conversion. The regulator compounds are defined by according to anyone of the Formulas 1A, 1B, 1C, 1D, 1E, 1F, 1G, 1H and 1I: ##STR00001## wherein R.sup.1 stands for an optionally substituted secondary or tertiary alkyl or secondary or tertiary aralkyl; Z.sup.1 stands for CN or a carboxylic acid ester of formula C(O)OR.sup.21; Z.sup.2 may be chosen from the group of CN, carboxylic acid, salts of carboxylic acids, carboxylic acid ester, carboxylic acid amides, (hetero)aryl, alkenyl and halogen; R.sup.2, R.sup.3, R.sup.4 and R.sup.5 are each independently chosen from the group of H, alkyl, aralkyl, (hetero)aryl, CN and carboxylic acid ester of formula C(O)OR.sup.22; R.sup.7 stands for a primary alkyl or primary aralkyl, CN or hydrogen; Y stands for a bridging group and n is 2, 3, 4, 5 or 6; in case R.sup.1 stands for tertiary alkyl or tertiary aralkyl, R.sup.6 stands for a primary alkyl or primary aralkyl, CN or a carboxylic acid ester of formula C(O)OR.sup.26; in case R.sup.1 stands for a secondary alkyl or secondary aralkyl, R.sup.6 stands for a primary or secondary alkyl or primary or secondary aralkyl, CN, a carboxylic acid ester of formula C(O)OR.sup.26 or a phosphonic acid ester of formula P(O)(OR.sup.27).sub.2, a (hetero)aryl or an alkenyl; R.sup.21, R.sup.22, R.sup.26 and R.sup.27 each independently stand for alkyl or aralkyl having from 1-30 carbon atoms, optionally containing heteroatoms.

New regulator compounds for a novel polymerization process for vinyl monomers, which yields polymers with improved control over composition and nearly full to full conservation of architectural integrity up to high conversion. The regulator compounds are defined by according to anyone of the Formulas 1A, 1B, 1C, 1D, 1E, 1F, 1G, 1H and 1I: ##STR00001## wherein R.sup.1 stands for an optionally substituted secondary or tertiary alkyl or secondary or tertiary aralkyl; Z.sup.1 stands for CN or a carboxylic acid ester of formula C(O)OR.sup.21; Z.sup.2 may be chosen from the group of CN, carboxylic acid, salts of carboxylic acids, carboxylic acid ester, carboxylic acid amides, (hetero)aryl, alkenyl and halogen; R.sup.2, R.sup.3, R.sup.4 and R.sup.5 are each independently chosen from the group of H, alkyl, aralkyl, (hetero)aryl, CN and carboxylic acid ester of formula C(O)OR.sup.22; R.sup.7 stands for a primary alkyl or primary aralkyl, CN or hydrogen; Y stands for a bridging group and n is 2, 3, 4, 5 or 6; in case R.sup.1 stands for tertiary alkyl or tertiary aralkyl, R.sup.6 stands for a primary alkyl or primary aralkyl, CN or a carboxylic acid ester of formula C(O)OR.sup.26; in case R.sup.1 stands for a secondary alkyl or secondary aralkyl, R.sup.6 stands for a primary or secondary alkyl or primary or secondary aralkyl, CN, a carboxylic acid ester of formula C(O)OR.sup.26 or a phosphonic acid ester of formula P(O)(OR.sup.27).sub.2, a (hetero)aryl or an alkenyl; R.sup.21, R.sup.22, R.sup.26 and R.sup.27 each independently stand for alkyl or aralkyl having from 1-30 carbon atoms, optionally containing heteroatoms.

The present invention provides lipids and lipid nanoparticle formulations comprising these lipids, alone or in combination with other lipids. These lipid nanoparticles may be formulated with nucleic acids to facilitate their intracellular delivery both in vitro and for therapeutic applications. The present invention also provides methods of chemical synthesis of these lipids, lipid nanoparticle preparation and formulation with nucleic acids.

New regulator compounds for a novel polymerization process for vinyl monomers, which yields polymers with improved control over composition and nearly full to full conservation of architectural integrity up to high conversion. The regulator compounds are defined by according to anyone of the Formulas 1A, 1B, 1C, 1D, 1E, 1F, 1G, 1H and 1I:

##STR00001## wherein R.sup.1 stands for an optionally substituted secondary or tertiary alkyl or secondary or tertiary aralkyl; Z.sup.1 stands for CN or a carboxylic acid ester of formula C(O)OR.sup.21; Z.sup.2 may be chosen from the group of CN, carboxylic acid, salts of carboxylic acids, carboxylic acid ester, carboxylic acid amides, (hetero)aryl, alkenyl and halogen; R.sup.2, R.sup.3, R.sup.4 and R.sup.5 are each independently chosen from the group of H, alkyl, aralkyl, (hetero)aryl, CN and carboxylic acid ester of formula C(O)OR.sup.22; R.sup.7 stands for a primary alkyl or primary aralkyl, CN or hydrogen; Y stands for a bridging group and n is 2, 3, 4, 5 or 6; in case R.sup.1 stands for tertiary alkyl or tertiary aralkyl, R.sup.6 stands for a primary alkyl or primary aralkyl, CN or a carboxylic acid ester of formula C(O)OR.sup.26; in case R.sup.1 stands for a secondary alkyl or secondary aralkyl, R.sup.6 stands for a primary or secondary alkyl or primary or secondary aralkyl, CN, a carboxylic acid ester of formula C(O)OR.sup.26 or a phosphonic acid ester of formula P(O)(OR.sup.27).sub.2, a (hetero)aryl or an alkenyl; R.sup.21, R.sup.22, R.sup.26 and R.sup.27 each independently stand for alkyl or aralkyl having from 1-30 carbon atoms, optionally containing heteroatoms.