Abstract: Provided herein are methods for preparing ketone-containing organic molecules. The methods are based on novel iron/copper-mediated (“Fe/Cu-mediated”) coupling reactions. The Fe/Cu-mediated coupling reaction can be used in the preparation of complex molecules, such as halichondrins and analogs thereof. In particular, the Fe/Cu-mediated ketolization reactions described herein are useful in the preparation of intermediates en route to halichondrins.

Abstract: The present invention provides novel Compound (1) having tumor vascular remodeling effect and/or anti-CAF (Cancer Associated Fibroblasts) activity, or a pharmaceutically acceptable salt thereof, optionally in a pharmaceutically acceptable and medical uses thereof.

Abstract: The present invention provides unified synthesis of the CI-CI 9 building blocks of halichondrins and analogs thereof using selective coupling of poly-halogenated nucleophiles in chromium-mediated coupling reactions. The present invention also provides a practical and efficient synthesis of C20-C38 building blocks of halichondrins and analogs thereof. Also provided herein are general methods of selective activation and coupling of poly-halogenated analogs with an aldehyde. The provided coupling reactions are selective for halo-enone and halo-acetylenic ketal over vinyl halide and halide attached to a sp hydridized carbon. The provided efficient selective coupling reactions can allow easy access to the CI-CI 9 building blocks and C20-C38 building blocks of halichondrins and analogs thereof with limited or no purification or separation of the intermediates.

Abstract: The present invention provides halichondrin analogs, such as compounds of Formula (I). The compounds may bind to microtubule sites, thereby inhibiting microtubule dynamics. Also provided are methods of synthesis, pharmaceutical compositions, kits, methods of treatment, and uses that involve the compounds for treatment of a proliferative disease (e.g., cancer). Compounds of the present invention are particularly useful for the treatment of metastatic breast cancer, non-small cell lung cancer, prostate cancer, and sarcoma. The included methods of synthesis are useful for the preparation of compounds of Formula (I)-(III) along with naturally occurring halicondrins (e.g., halichondrin B & C, norhalichondrin A, B, & C, and homohalichondrin A, B, & C). Also included are methods for interconverting between the halichondrins, norhalichondrins, and homohalichondrins and their unnatural epimers at the C38 ketal stereocenter through the use of an acid-mediated equilibration.

Abstract: The present invention provides unified synthesis of the C1-C19 building blocks of halichondrins and analogs thereof using selective coupling of poly-halogenated nucleophiles in chromium-mediated coupling reactions. The present invention also provides a practical and efficient synthesis of C20-C38 building blocks of halichondrins and analogs thereof. Also provided herein are general methods of selective activation and coupling of poly-halogenated analogs with an aldehyde. The provided coupling reactions are selective for halo-enone and halo-acetylenic ketal over vinyl halide and halide attached to a sp hybridized carbon. The provided efficient selective coupling reactions can allow easy access to the C1-C19 building blocks and C20-C38 building blocks of halichondrins and analogs thereof with limited or no purification or separation of the intermediates.

Abstract: Provided herein are palladium-mediated coupling reactions useful in the preparation of ketone-containing organic molecules. The provided methods can be used for the preparation of natural products and pharmaceutical agents, including Eribulin, halichondrins, and analogs thereof. The present invention also provides novel halichondrin analogs which can be prepared via the palladium-mediated coupling reactions. The novel halichondrin analogs can be used in the prevention and/or treatment of diseases or conditions (e.g., proliferative diseases such as cancer).

Abstract: Provided herein are palladium-mediated coupling reactions useful in the preparation of ketone-containing organic molecules. The provided methods can be used for the preparation of natural products and pharmaceutical agents, including Eribulin, halichondrins, and analogs thereof. The present invention also provides novel halichondrin analogs which can be prepared via the palladium-mediated coupling reactions. The novel halichondrin analogs can be used in the prevention and/or treatment of diseases or conditions (e.g., proliferative diseases such as cancer).

Abstract: The present invention provides unified synthesis of the CI-CI 9 building blocks of halichondrins and analogs thereof using selective coupling of poly-halogenated nucleophiles in chromium-mediated coupling reactions. The present invention also provides a practical and efficient synthesis of C20-C38 building blocks of halichondrins and analogs thereof. Also provided herein are general methods of selective activation and coupling of poly-halogenated analogs with an aldehyde. The provided coupling reactions are selective for halo-enone and halo-acetylenic ketal over vinyl halide and halide attached to a sp hydridized carbon. The provided efficient selective coupling reactions can allow easy access to the CI-CI 9 building blocks and C20-C38 building blocks of halichondrins and analogs thereof with limited or no purification or separation of the intermediates.

Abstract: The present invention provides unified synthesis of the CI-CI 9 building blocks of halichondrins and analogs theoreof using selective coupling of poly-halogenated nucleophiles in chromium-mediated coupling reactions. The present invention also provides a practical and efficient synthesis of C20-C38 building blocks of halichondrins and analogs thereof. Also provided herein are general methods of selective activation and coupling of poly-halogenated analogs with an aldehyde. The provided coupling reactions are selective for halo-enone and halo-acetylenic ketal over vinyl halide and halide attached to a sp hydridized carbon. The provided efficient selective coupling reactions can allow easy access to the CI-CI 9 building blocks and C20-C38 building blocks of halichondrins and analogs thereof with limited or no purification or separation of the intermediates.

Abstract: Provided herein are palladium-mediated coupling reactions useful in the preparation of ketone-containing organic molecules. The provided methods can be used for the preparation of natural products and pharmaceutical agents, including Eribulin, halichondrins, and analogs thereof. The present invention also provides novel halichondrin analogs which can be prepared via the palladium-mediated coupling reactions. The novel halichondrin analogs can be used in the prevention and/or treatment of diseases or conditions (e.g., proliferative diseases such as cancer).

Abstract: The present invention provides novel Compound (1) having tumor vascular remodeling effect and/or anti-CAF (Cancer Associated Fibroblasts) activity, or a pharmaceutically acceptable salt thereof, optionally in a pharmaceutically acceptable carrier, and a medical uses thereof.

Abstract: The present invention provides halichondrin analogs, such as compounds of Formula (I). The compounds may bind to microtubule sites, thereby inhibiting microtubule dynamics. Also provided are methods of synthesis, pharmaceutical compositions, kits, methods of treatment, and uses that involve the compounds for treatment of a proliferative disease (e.g., cancer). Compounds of the present invention are particularly useful for the treatment of metastatic breast cancer, non-small cell lung cancer, prostate cancer, and sarcoma. The included methods of synthesis are useful for the preparation of compounds of Formula (I)-(III) along with naturally occurring halicondrins (e.g., halichondrin B & C, norhalichondrin A, B, & C, and homohalichondrin A, B, & C). Also included are methods for interconverting between the halichondrins, norhalichondrins, and homohalichondrins and their unnatural epimers at the C38 ketal stereocenter through the use of an acid-mediated equilibration.

Abstract: Novel chemical compounds that can be used to synthesize halichondrin B and norhalichondrin B, and related derivatives. The total synthesis of halichondrin B and norhalichondrin B is also disclosed.

Abstract: Enterobactin analogs prepared from scyllo-inositol mono-orthoformate and having the following formula: ##STR1## wherein each X.sub.1, X.sub.2 and X.sub.3, independently, is H, C.sub.1-20 alkyl, phenyl, naphthyl, C.sub.7-20 aralkyl, or C.sub.7-20 alkaryl; Y is H, C.sub.1-20 alkyl, phenyl, naphthyl; C.sub.7-20 aralkyl, C.sub.7-20 alkaryl; --(C.sub.p H.sub.2p)--CH.sub.2 OH, --(C.sub.p H.sub.2p)--COOH or its salt, --(C.sub.p H.sub.2p)--NR.sub.1.R.sub.2 or its salt, or --(C.sub.p H.sub.2p)--N.sup.+ R.sub.1.R.sub.2.R.sub.3 ; in which p is 1-20 and each R.sub.1, R.sub.2 and R.sub.3, independently, is H or C.sub.1-5 alkyl; and m, n and o, independently, is 1-6; or the enantiomer thereof.

Abstract: Novel chemical compounds that can be used to synthesize halichondrin B and norhalichondrin B, and related derivatives, are described. The synthesis of halichondrin B and norhalichondrin B from these compounds also is described.

Abstract: A new compound of the formula ##STR1## wherein R.sup.1 is a hydrogen atom, a hydroxyl group or an alkoxyl group of 1-4 carbon atoms and R.sup.2 is an ethyl group or acetyl group is now provided, which is an intermediate compound useful for synthesis of antitumor anthracyclines. This new anthracycline is produced by cyclization of a new compound of the formula ##STR2## wherein R.sup.1 is as defined above and TMS denotes a trimethylsilyl group, followed by decarboxylation of the cyclization product.

Abstract: A compound of the formula ##STR1## wherein R.sub.1 is lower alkyl, aryloxy(lower)alkyl or ar(lower)alkyl,R.sub.2 is lower alkyl,Coor.sub.3 is esterified carboxy selected from lower alkoxycarbonyl and ar(lower)alkoxycarbonyl,X is halogen selected from bromine and chlorine, andX' is hydrogen or halogen selected from bromine and chlorine,Said aryl and said ar each constituting phenyl, tolyl or xylyl, and a method of making it are disclosed.