The invention relates to a method for the preparation of cyclic compounds in the metathesis of olefins from acyclic dienes comprising terminal and/or non-terminal C═C double bonds; the invention also relates to the use of homogeneous ruthenium complexes and homogeneous ruthenium complexes deposited on a solid support as catalysts and/or pre-catalysts for the preparation of cyclic olefins in olefin metathesis reactions.

Pharmaceutical compositions of the invention comprise functionalized lactone derivatives having a disease-modifying action in the treatment of diseases associated with dysregulation of 5-hydroxytryptamine receptor 7 activity.

Pharmaceutical compositions of the invention comprise functionalized lactone derivatives having a disease-modifying action in the treatment of diseases associated with dysregulation of 5-hydroxytryptamine receptor 7 activity.

Provided herein are the K-Ras inhibitors of the formulae: ##STR00001##
Also provided are compositions comprising thereof for treating cancer.

The present disclosure provides compositions and methods for metathesizing a first alkenyl or alkynyl group with a second alkenyl or alkynyl group, the composition comprising a ruthenium metathesis catalyst and a photoredox catalyst that is activated by visible light.

Disclosed are an intermediate of Eribulin and a preparation method therefor. In particular, disclosed are compounds as represented by formula II, formula III and formula V and a preparation method therefor. Ar is C.sub.1-10 alkyl substituted, alkyloxy substituted or unsubstituted aryl; R.sup.1 and R.sup.2 is an acetal protecting group or a thioacetal protecting group; R.sup.3 is hydrogen or a hydroxyl protecting group; and X is halogen or a leaving group. The preparation method therefor has the advantages of mild reaction conditions, high selectivity, easy purification, low synthesis cost and the like, being suitable for large scale production. ##STR00001##

Disclosed are an intermediate of Eribulin and a preparation method therefor. In particular, disclosed are compounds as represented by formula II, formula III and formula V and a preparation method therefor. Ar is C.sub.1-10 alkyl substituted, alkyloxy substituted or unsubstituted aryl; R.sup.1 and R.sup.2 is an acetal protecting group or a thioacetal protecting group; R.sup.3 is hydrogen or a hydroxyl protecting group; and X is halogen or a leaving group. The preparation method therefor has the advantages of mild reaction conditions, high selectivity, easy purification, low synthesis cost and the like, being suitable for large scale production. ##STR00001##

The invention provides methods for the synthesis of eribulin or a pharmaceutically acceptable salt thereof (e.g., eribulin mesylate) through a macrocyclization strategy. The macrocyclization strategy of the present invention involves subjecting a non-macrocyclic intermediate to a carbon-carbon bond-forming reaction (e.g., an olefination reaction (e.g., Homer-Wadsworth-Emmons olefination), Dieckmann reaction, catalytic Ring-Closing Olefin Metathesis, or Nozaki-Hiyama-Kishi reaction) to afford a macrocyclic intermediate. The invention also provides compounds useful as intermediates in the synthesis of eribulin or a pharmaceutically acceptable salt thereof and methods for preparing the same.

The invention provides methods for the synthesis of eribulin or a pharmaceutically acceptable salt thereof (e.g., eribulin mesylate) through a macrocyclization strategy. The macrocyclization strategy of the present invention involves subjecting a non-macrocyclic intermediate to a carbon-carbon bond-forming reaction (e.g., an olefination reaction (e.g., Homer-Wadsworth-Emmons olefination), Dieckmann reaction, catalytic Ring-Closing Olefin Metathesis, or Nozaki-Hiyama-Kishi reaction) to afford a macrocyclic intermediate. The invention also provides compounds useful as intermediates in the synthesis of eribulin or a pharmaceutically acceptable salt thereof and methods for preparing the same.

The invention provides methods utilizing Prins reaction in the preparation of compounds that may be useful as intermediates in the synthesis of halichondrin macrolides and analogs thereof. The invention also provides compounds that may be useful as intermediates in the synthesis of a halichondrin macrolides and methods for preparing the same.