Arylfluorosulfate compounds derived from anticancer drugs are disclosed herein, which exhibit improved anti-cancer cell proliferation activities compared to their phenolic drug precursors. Among these compounds, the fluorosulfate derivative of fulvestrant showed significantly enhanced activity to down-regulate estrogen receptor (ER) expression in ER.sup.+ breast cancer cell line MCF-7, and oral availability in vivo; the fluorosulfate derivative of combretastatin A4 exhibited a 70-fold increase in potency in the drug resistant colon cancer cell line HT-29; and the fluorosulfate derivative of ABT-751 showed enhanced activity relative to ABT-751.

Disclosed herein are compounds of formula ArN(SO.sub.2F).sub.2, wherein Ar is selected from an optionally substituted aryl, an optionally substituted five-membered heteroaryl, or an optionally substituted six-membered heteroaryl. Also disclosed are methods of synthesizing the above compounds by reacting a compound of formula ArNHR.sub.9 with MN(SO.sub.2F).sub.2.

Disclosed herein are compounds of formula ArN(SO.sub.2F).sub.2, wherein Ar is selected from an optionally substituted aryl, an optionally substituted five-membered heteroaryl, or an optionally substituted six-membered heteroaryl. Also disclosed are methods of synthesizing the above compounds by reacting a compound of formula ArNHR.sub.9 with MN(SO.sub.2F).sub.2.

This application describes a compound represented by Formula (I):

Y?Z?X.sup.1S(O)(X.sup.2)F).sub.m].sub.n(I)

wherein: Y is a biologically active organic core group comprising one or more of an aryl group, a heteroaryl aryl group, a nonaromatic hydrocarbyl group, and a nonaromatic heterocyclic group, to which Z is covalently bonded; n is 1, 2, 3, 4 or 5; m is 1 or 2; Z is O, NR, or N; X.sup.1 is a covalent bond or CH.sub.2CH.sub.2, X.sup.2 is O or NR; and R comprises H or a substituted or unsubstituted group selected from an aryl group, a heteroaryl aryl group, a nonaromatic hydrocarbyl group, and a nonaromatic heterocyclic group. Methods of preparing the compounds, methods of using the compounds, and pharmaceutical compositions comprising the compounds are described as well.

This application describes a compound represented by Formula (I):

Y?Z?X.sup.1S(O)(X.sup.2)F).sub.m].sub.n(I)

wherein: Y is a biologically active organic core group comprising one or more of an aryl group, a heteroaryl aryl group, a nonaromatic hydrocarbyl group, and a nonaromatic heterocyclic group, to which Z is covalently bonded; n is 1, 2, 3, 4 or 5; m is 1 or 2; Z is O, NR, or N; X.sup.1 is a covalent bond or CH.sub.2CH.sub.2, X.sup.2 is O or NR; and R comprises H or a substituted or unsubstituted group selected from an aryl group, a heteroaryl aryl group, a nonaromatic hydrocarbyl group, and a nonaromatic heterocyclic group. Methods of preparing the compounds, methods of using the compounds, and pharmaceutical compositions comprising the compounds are described as well.

Provided herein are inter alia, unnatural amino acids based on fluorosulfonyloxybenzoyl-L-lysine FSK, proteins comprising unnatural amino acids, nanobodies comprising unnatural amino acids based on fluorosulfate-L-tyrosine FSY, meta-FSY and FFY within CDR1, CDR2, or CDR3, biomolecule conjugates, and methods of making the proteins and biomolecule conjugates.

Provided herein are inter alia, unnatural amino acids based on fluorosulfonyloxybenzoyl-L-lysine FSK, proteins comprising unnatural amino acids, nanobodies comprising unnatural amino acids based on fluorosulfate-L-tyrosine FSY, meta-FSY and FFY within CDR1, CDR2, or CDR3, biomolecule conjugates, and methods of making the proteins and biomolecule conjugates.

This application describes a compound represented by Formula (I): (I) wherein: Y is a biologically active organic core group comprising one or more of an aryl group, a heteroaryl aryl group, a nonaromatic hydrocarbyl group, and a nonaromatic heterocyclic group, to which Z is covalently bonded; n is 1, 2, 3, 4 or 5; m is 1 or 2; Z is O, NR, or N; X.sup.1 is a covalent bond or CH.sub.2CH.sub.2, X.sup.2 is O or NR; and R comprises H or a substituted or unsubstituted group selected from an aryl group, a heteroaryl aryl group, a nonaromatic hydrocarbyl group, and a nonaromatic heterocyclic group. Methods of preparing the compounds, methods of using the compounds, and pharmaceutical compositions comprising the compounds are described as well.

This application describes a compound represented by Formula (I): (I) wherein: Y is a biologically active organic core group comprising one or more of an aryl group, a heteroaryl aryl group, a nonaromatic hydrocarbyl group, and a nonaromatic heterocyclic group, to which Z is covalently bonded; n is 1, 2, 3, 4 or 5; m is 1 or 2; Z is O, NR, or N; X.sup.1 is a covalent bond or CH.sub.2CH.sub.2, X.sup.2 is O or NR; and R comprises H or a substituted or unsubstituted group selected from an aryl group, a heteroaryl aryl group, a nonaromatic hydrocarbyl group, and a nonaromatic heterocyclic group. Methods of preparing the compounds, methods of using the compounds, and pharmaceutical compositions comprising the compounds are described as well.

In one aspect, there is provided a method of coupling an aromatic compound having a fluorosulfonate substituent to an alkyne. In another aspect, there is provided a method of coupling an aromatic compound having a hydroxyl substituent to an alkyne in a one-pot reaction.