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., Horner-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., Horner-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.

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.

Chromophores with large hyperpolarizabilities, films with electro-optic activity comprising the chromophores, and electro-optic devices comprising the chromophores are disclosed.

Chromophores with large hyperpolarizabilities, films with electro-optic activity comprising the chromophores, and electro-optic devices comprising the chromophores are disclosed.

The present invention pertains generally to the field of therapeutic compounds. More specifically the present invention pertains to certain 2-amino-N-(amino-oxo-aryl-λ.sup.6-sulfanylidene)acetamide compounds (referred to herein as ANASIA compounds) that, inter alia, inhibit (e.g., selectively inhibit) bacterial aminoacyl-tRNA synthetase (aaRS) (e.g., bacterial leucyl-tRNA synthetase, LeuRS). The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit (e.g., selectively inhibit) bacterial aminoacyl-tRNA synthetase; to treat disorders that are ameliorated by the inhibition (e.g., selective inhibition) of bacterial aminoacyl-tRNA synthetase; to treat bacterial infections; etc.

##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##

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##

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.