Methods and uses for enhancing or restoring the antitumor response, such as the antitumor immune mediated by immune checkpoint inhibitors, in cancer patients, are described. These methods are based on the administration of castalagin or analogs thereof, and are particularly useful for the treatment of tumors resistant to immunotherapy such as immune checkpoint inhibitor therapy. The castalagin or analog thereof may be administered in any suitable form, for example in a crude plant or fruit extract such as a Myrciaria dubia extract, or in a pharmaceutical composition

The present invention provides methods for the synthesis of ketones involving a Ni/Zr-mediated coupling reaction. The Ni/Zr-mediated ketolization reactions can be used in the synthesis of halichondrins (e.g., halichondrin A, B, C; homohalichondrin A, B, C; norhalichondrin A, B, C), and analogs thereof. Therefore, the present invention also provides synthetic methods useful for the synthesis of halichondrins, and analogs thereof. Also provided herein are compounds (i.e., intermediates) useful in the synthesis of halichondrins, and analogs thereof. In particular, the present invention provides methods and compounds useful in the synthesis of compound of Formula (H3-A):

##STR00001##

The present invention provides methods for the synthesis of ketones involving a Ni/Zr-mediated coupling reaction. The Ni/Zr-mediated ketolization reactions can be used in the synthesis of halichondrins (e.g., halichondrin A, B, C; homohalichondrin A, B, C; norhalichondrin A, B, C), and analogs thereof. Therefore, the present invention also provides synthetic methods useful for the synthesis of halichondrins, and analogs thereof. Also provided herein are compounds (i.e., intermediates) useful in the synthesis of halichondrins, and analogs thereof. In particular, the present invention provides methods and compounds useful in the synthesis of compound of Formula (H3-A):

##STR00001##

Provided is a compound of Chemical Formula 1: ##STR00001##
and an organic light emitting device comprising the same.

Provided is a compound of Chemical Formula 1: ##STR00001##
and an organic light emitting device comprising the same.

The present disclosure relates to a drug conjugate of an Eribulin derivative, a preparation method therefor and an application thereof in medicine. Specifically, provided is an antibody-drug conjugate, which contains an Eribulin derivative drug portion. The present disclosure further relates to a method for treating cancer by administering the antibody-drug conjugate provided herein.

A compound of Formula I:

##STR00001##

wherein: X.sup.1-X.sup.8 are each independently C or N, wherein two adjacent X.sup.1-X.sup.8 are carbon-fused to a structure of Formula II:

##STR00002## X.sup.9-X.sup.12 are each independently C or N; A.sup.1, A.sup.2, and A.sup.3 are each independently selected from the group consisting of O, S, Se, N, NR, CR, CRR′, SiR, SiRR′, GeR, and GeRR′, with at least one of A.sup.1 and A.sup.2 being N or NR; each occurrence of is independently a single bond or a double bond, wherein one occurrence of is a single bond and one occurrence of is a double bond; each of R.sup.A, R.sup.B, and R.sup.C independently represents zero, mono, or up to a maximum allowed substitution to its associated ring; each of occurrence R, R′, R.sup.A, R.sup.B, and R.sup.C is independently a hydrogen or a substituent selected from the group consisting of Formula III, Formula IV, Formula V, Formula VI, Formula VII, Formula VIII, Formula IX, deuterium, halogen, alkyl, cycloalkyl, heteroalkyl, heterocycloalkyl, arylalkyl, alkoxy, aryloxy, amino, silyl, boryl, alkenyl, cycloalkenyl, heteroalkenyl, alkynyl, aryl, heteroaryl, acyl, carboxylic acid, ether, ester, nitrile, isonitrile, sulfanyl, sulfinyl, sulfonyl, phosphino, and combinations thereof, with at least one of R, R′, R.sup.A, R.sup.B, and R.sup.C comprising a group of Formula III, Formula IV, Formula V, Formula VI, Formula VII, Formula VIII, or Formula IX:

##STR00003## ##STR00004## each occurrence of Y.sup.1, Y.sup.2, and Y.sup.3 is independently absent, O, S, Se, NR, CRR′, SiRR′, or GeRR′; each occurrence of Ar.sup.1, and Ar.sup.2 is independently an optionally substituted aryl group or an optionally substituted heteroaryl group, wherein Ar.sup.1 and Ar.sup.2 are optionally joined or fused together to form a ring; each occurrence of X.sup.13-X.sup.20 is independently C or N, with the proviso that at least one of X.sup.13-X.sup.20 is N; each occurrence of A.sup.4 is selected from the group consisting of O, S, Se, NR, CRR′, SiRR′, and GeRR′; each occurrence of R.sup.X independently represents zero, mono, or up to a maximum allowed substitution to its associated ring; eac

A compound of Formula I:

##STR00001##

wherein: X.sup.1-X.sup.8 are each independently C or N, wherein two adjacent X.sup.1-X.sup.8 are carbon-fused to a structure of Formula II:

##STR00002## X.sup.9-X.sup.12 are each independently C or N; A.sup.1, A.sup.2, and A.sup.3 are each independently selected from the group consisting of O, S, Se, N, NR, CR, CRR′, SiR, SiRR′, GeR, and GeRR′, with at least one of A.sup.1 and A.sup.2 being N or NR; each occurrence of is independently a single bond or a double bond, wherein one occurrence of is a single bond and one occurrence of is a double bond; each of R.sup.A, R.sup.B, and R.sup.C independently represents zero, mono, or up to a maximum allowed substitution to its associated ring; each of occurrence R, R′, R.sup.A, R.sup.B, and R.sup.C is independently a hydrogen or a substituent selected from the group consisting of Formula III, Formula IV, Formula V, Formula VI, Formula VII, Formula VIII, Formula IX, deuterium, halogen, alkyl, cycloalkyl, heteroalkyl, heterocycloalkyl, arylalkyl, alkoxy, aryloxy, amino, silyl, boryl, alkenyl, cycloalkenyl, heteroalkenyl, alkynyl, aryl, heteroaryl, acyl, carboxylic acid, ether, ester, nitrile, isonitrile, sulfanyl, sulfinyl, sulfonyl, phosphino, and combinations thereof, with at least one of R, R′, R.sup.A, R.sup.B, and R.sup.C comprising a group of Formula III, Formula IV, Formula V, Formula VI, Formula VII, Formula VIII, or Formula IX:

##STR00003## ##STR00004## each occurrence of Y.sup.1, Y.sup.2, and Y.sup.3 is independently absent, O, S, Se, NR, CRR′, SiRR′, or GeRR′; each occurrence of Ar.sup.1, and Ar.sup.2 is independently an optionally substituted aryl group or an optionally substituted heteroaryl group, wherein Ar.sup.1 and Ar.sup.2 are optionally joined or fused together to form a ring; each occurrence of X.sup.13-X.sup.20 is independently C or N, with the proviso that at least one of X.sup.13-X.sup.20 is N; each occurrence of A.sup.4 is selected from the group consisting of O, S, Se, NR, CRR′, SiRR′, and GeRR′; each occurrence of R.sup.X independently represents zero, mono, or up to a maximum allowed substitution to its associated ring; eac

Disclosed is a compound of formula 1, or a pharmaceutically acceptable salt thereof, where R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.7′, R.sup.8, R.sup.9, R.sup.10, R.sup.11, R.sup.12 and R.sup.13 are as disclosed herein. Also, disclosed is a process for the preparation of the compound of formula 1, or a pharmaceutically acceptable salt thereof, and intermediates used therein. The compound of formula 1 can be used in the preparation of halichondrin analogs, such as Eribulin; and a process for its preparation from the compound of formula 1 is also disclosed. ##STR00001##

Disclosed is a compound of formula 1, or a pharmaceutically acceptable salt thereof, where R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.7′, R.sup.8, R.sup.9, R.sup.10, R.sup.11, R.sup.12 and R.sup.13 are as disclosed herein. Also, disclosed is a process for the preparation of the compound of formula 1, or a pharmaceutically acceptable salt thereof, and intermediates used therein. The compound of formula 1 can be used in the preparation of halichondrin analogs, such as Eribulin; and a process for its preparation from the compound of formula 1 is also disclosed. ##STR00001##