# US 2016/0257707 A1 · Taccalonolide microtubule stabilizers

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- Number: US 2016/0257707 A1
- Document ID: US20160257707A1
- Status: Published application
- Kind: A1
- Application number: 15/153,470
- Filed: 2016-05-12
- Published: 2016-09-08
- Earliest claimed: 2011-06-06
- Assignees: Board of Regents, The University of Texas System
- Applicants: The Board of Regents of the University of Texas System
- Inventors: Susan L. MOOBERRY; Jiangnan PENG; April L. RISINGER; Jing LI
- Web page: https://patentgrep.com/patent/US20160257707A1

## CPC

- C07J 71/001: {Oxiranes}
- A61K 31/585: containing lactone rings, e.g. oxandrolone, bufalin
- A61K 36/894: Dioscoreaceae (Yam family)
- A61P 35/00: Antineoplastic agents
- C07D 493/08: Bridged systems
- C07J 71/0005: {Oxygen-containing hetero ring}
- C07J: STEROIDS (seco-steroids C07C)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)

## Abstract

The invention provides epoxytaccalonolide microtubule stabilizers and their use as anti-proliferative microtubule stabilizing agents.

## Claims

### Claim 1

A compound of the formula:
wherein:
R1 is hydrogen, amino, cyano, azido, halo, hydroxy, oxo, alkyl(C≦12), alkenyl(C≦12), alkoxy(C≦12), acyl(C≦12), acyloxy(C≦12), alkylamino(C≦12), dialkylamino(C≦12), amido(C≦12), alkylthio(C≦12), aryl(C≦12), aralkyl(C≦12), heterocycloalkyl(C≦12), or substituted versions thereof;
R2 is hydrogen, amino, cyano, azido, halo, hydroxy, oxo, alkyl(C≦12), alkenyl(C≦12), alkoxy(C≦12), acyl(C≦12), acyloxy(C≦12), alkylamino(C≦12), dialkylamino(C≦12), amido(C≦12), alkylthio(C≦12), aryl(C≦12), aralkyl(C≦12), heterocycloalkyl(C≦12), or substituted versions thereof, or R2 is taken together with R3 to form an epoxide at C-2/C-3;
R3 is hydrogen, amino, cyano, azido, halo, hydroxy, oxo, alkyl(C≦12), alkenyl(C≦12), alkoxy(C≦12), acyl(C≦12), acyloxy(C≦12), alkylamino(C≦12), dialkylamino(C≦12), amido(C≦12), alkylthio(C≦12), aryl(C≦12), aralkyl(C≦12), heterocycloalkyl(C≦12), and substituted versions thereof, or R3 is taken together with R2 as defined above;
R5 is absent, hydrogen, amino, cyano, azido, halo, hydroxy, alkyl(C≦12), alkenyl(C≦12), alkoxy(C≦12), acyl(C≦12), acyloxy(C≦12), alkylamino(C≦12), dialkylamino(C≦12), amido(C≦12), alkylthio(C≦12), aryl(C≦12), aralkyl(C≦12), heterocycloalkyl(C≦12), or substituted versions thereof;
R6 is hydrogen, amino, cyano, azido, halo, hydroxy, alkyl(C≦12), alkenyl(C≦12), alkoxy(C≦12), acyl(C≦12), acyloxy(C≦12), alkylamino(C≦12), dialkylamino(C≦12), amido(C≦12), alkylthio(C≦12), aryl(C≦12), aralkyl(C≦12), heterocycloalkyl(C≦12), or substituted versions thereof, or oxo if R6′ is not present, or R6 is taken together with R7 to form an epoxide at C-6/C-7;
R6′ when present is hydrogen, amino, cyano, azido, halo, hydroxy, alkenyl(C≦12), alkoxy(C≦12), acyl(C≦12), acyloxy(C≦12), alkylamino(C≦12), dialkylamino(C≦12), amido(C≦12), alkylthio(C≦12), aryl(C≦12), aralkyl(C≦12), heterocycloalkyl(C≦12), or substituted versions thereof;
R7 is hydrogen, amino, cyano, azido, halo, hydroxy, alkyl(C≦12), alkenyl(C≦12), alkoxy(C≦12), acyl(C≦12), acyloxy(C≦12), alkylamino(C≦12), dialkylamino(C≦12), amido(C≦12), alkylthio(C≦12), aryl(C≦12), aralkyl(C≦12), heterocycloalkyl(C≦12), or substituted versions thereof, or oxo if R7′ is not present, or R7 is taken together with R6 as defined above;
R7′ when present is hydrogen, amino, cyano, azido, halo, hydroxy, alkenyl(C≦12), alkoxy(C≦12), acyl(C≦12), acyloxy(C≦12), alkylamino(C≦12), dialkylamino(C≦12), amido(C≦12), alkylthio(C≦12), aryl(C≦12), aralkyl(C≦12), heterocycloalkyl(C≦12), or substituted versions thereof;
R11 is hydrogen, amino, cyano, azido, halo, hydroxy, alkyl(C≦12), alkenyl(C≦12), alkoxy(C≦12), acyl(C≦12), acyloxy(C≦12), alkylamino(C≦12), dialkylamino(C≦12), amido(C≦12), alkylthio(C≦12), aryl(C≦12), aralkyl(C≦12), heterocycloalkyl(C≦12), or substituted versions thereof;
R12 is hydrogen, amino, cyano, azido, halo, hydroxy, alkyl(C≦12), alkenyl(C≦12), alkoxy(C≦12), acyl(C≦12), acyloxy(C≦12), alkylamino(C≦12), dialkylamino(C≦12), amido(C≦12), alkylthio(C≦12), aryl(C≦12), aralkyl(C≦12), heterocycloalkyl(C≦12), or substituted versions thereof;
R15 is hydrogen, amino, cyano, azido, halo, hydroxy, oxo, alkyl(C≦12), alkenyl(C≦12), alkoxy(C≦12), acyl(C≦12), acyloxy(C≦12), alkylamino(C≦12), dialkylamino(C≦12), amido(C≦12), alkylthio(C≦12), aryl(C≦12), aralkyl(C≦12), heterocycloalkyl(C≦12), or substituted versions thereof;
R20 is hydrogen, amino, cyano, azido, halo, hydroxy, hydroperoxy, alkenyl(C≦12), alkoxy(C≦12), acyl(C≦12), acyloxy(C≦12), alkylamino(C≦12), dialkylamino(C≦12), amido(C≦12), alkylthio(C≦12), aryl(C≦12), aralkyl(C≦12), heterocycloalkyl(C≦12), or substituted versions thereof,
R21 is hydrogen, amino, cyano, azido, halo, hydroxy, alkyl(C≦12), alkenyl(C≦12), alkoxy(C≦12), acyl(C≦12), acyloxy(C≦12), alkylamino(C≦12), dialkylamino(C≦12), amido(C≦12), alkylthio(C≦12), aryl(C≦12), aralkyl(C≦12), heterocycloalkyl(C≦12), or substituted versions thereof,
R25 is hydrogen, amino, cyano, azido, halo, hydroxy, alkyl(C≦12), alkenyl(C≦12), alkoxy(C≦12), acyl(C≦12), acyloxy(C≦12), alkylamino(C≦12), dialkylamino(C≦12), amido(C≦12), alkylthio(C≦12), aryl(C≦12), aralkyl(C≦12), heterocycloalkyl(C≦12), or substituted versions thereof,
R26 is hydrogen, amino, cyano, azido, halo, hydroxy, alkyl(C≦12), alkenyl(C≦12), alkoxy(C≦12), acyl(C≦12), acyloxy(C≦12), alkylamino(C≦12), dialkylamino(C≦12), amido(C≦12), alkylthio(C≦12), aryl(C≦12), aralkyl(C≦12), heterocycloalkyl(C≦12), or substituted versions thereof, or oxo if R26′ is not present;
R26′ when present is hydrogen, amino, cyano, azido, halo, hydroxy, alkenyl(C≦12), alkoxy(C≦12), acyl(C≦12), acyloxy(C≦12), alkylamino(C≦12), dialkylamino(C≦12), amido(C≦12), alkylthio(C≦12), aryl(C≦12), aralkyl(C≦12), heterocycloalkyl(C≦12), or substituted versions thereof;
R27 is hydrogen, amino, cyano, azido, halo, hydroxy, alkyl(C≦12), alkenyl(C≦12), alkoxy(C≦12), acyl(C≦12), acyloxy(C≦12), alkylamino(C≦12), dialkylamino(C≦12), amido(C≦12), alkylthio(C≦12), aryl(C≦12), aralkyl(C≦12), heterocycloalkyl(C≦12), or substituted versions thereof; and
X is O, NR′ or CR′2, wherein each R′ is independently hydrogen or alkyl(C≦6);
or a pharmaceutically acceptable salt thereof,
wherein the —O— bridging C-22 and C-23 is optionally replaced with a double bond between C-22 and C-23;
provided, however, that Formula I does not include the compound wherein R1 is acetoxy, R2 taken together with R3 forms an epoxide at C-2/C-3; R5 is hydrogen, R6 is oxo and R6′ is not present, R7 is hydroxy and R7′ is hydrogen, each of R11, R12 and R15 are acetoxy, one of R20 or R21 is methyl and the other is hydrogen, R25 is OH, R26 is oxo and R26′ is not present, R27 is methyl, and X is O.

### Claim 2 (depends on 1)

The compound of claim 1, wherein:
R1 is hydroxy, alkoxy(C≦12) or acyloxy(C≦12);
R2 is hydroxy, halogen, alkoxy(C≦12) or acyloxy(C≦12), or R2 is taken together with R3 to form an epoxide at C-2/C-3;
R3 is hydroxy, halogen, alkoxy(C≦12) or acyloxy(C≦12), or R2 is taken together with R3 as defined above;
R5 is hydrogen, hydroxy, amino, alkoxy(C≦9), alkylamino(C≦6), or dialkylamino(C≦12);
R6 is hydrogen, hydroxy, alkoxy(C≦8), acyloxy(C≦8), amide(C≦12), alkylamino(C≦12), dialkylamino(C≦12), or oxo;
R6′ when present is hydrogen, hydroxy, alkoxy(C≦8), acyloxy(C≦8), amide(C≦12), alkylamino(C≦12) or dialkylamino(C≦12),
R7 is hydrogen, hydroxy, alkoxy(C≦8), acyloxy(C≦8), or oxo if R7′ is not present;
R7′ when present is hydrogen, hydroxy, alkoxy(C≦8), or acyloxy(C≦8);
R11 is hydrogen, hydroxy, alkoxy(C≦8), or acyloxy(C≦8);
R12 is hydrogen, hydroxy, alkoxy(C≦8), or acyloxy(C≦8);
R15 is hydrogen, hydroxy, alkoxy(C≦8) or acyloxy(C≦8);
R20 is hydrogen, methyl, hydroxy, hydroperoxy, alkoxy(C≦8) or acyloxy(C≦8);
R21 is hydrogen or methyl;
R25 is hydrogen, hydroxy, alkoxy(C≦8) or acyloxy(C≦8);
R26 is hydrogen, hydroxy, alkoxy(C≦8) or oxo if R26′ is not present;
R26′ when present is hydrogen, hydroxy or alkoxy(C≦8);
R27 is hydrogen or alkyl(C≦6); and
X is O, NR′ or CR′2, wherein each R′ is independently hydrogen or alkyl(C≦6);
or a pharmaceutically acceptable salt thereof.

### Claim 3 (depends on 1)

The compound of claim 1, wherein, R1 is acyloxy(C≦12), acetyloxy, isobutyrate, isovalerate, alkoxy, or hydroxy.

### Claim 4 (depends on 1)

The compound of claim 1, wherein one or both of R2 and/or R3 are acyloxy(C≦12), or R2 and R3, taken together, form an epoxide at C-2/C-3.

### Claim 5 (depends on 1)

The compound of claim 1, wherein R5 is hydrogen, hydroxy, alkoxy, acyloxy, or R5 is absent.

### Claim 6 (depends on 1)

The compound of claim 1, wherein R6 is oxo, hydroxy, acyloxy(C≦12), alkylamino(C≦12) or dialkylamino(C≦12), or R6 and R7, taken together, form an epoxide at C-6/C-7.

### Claim 7 (depends on 1)

The compound of claim 1, wherein R7 is acyloxy(C≦12), acetyloxy, hydroxy, alkoxy or oxo.

### Claim 8 (depends on 1)

The compound of claim 1, wherein R15 is hydroxy, alkoxy, hydrogen, oxo, acyloxy(C≦12), or acetyloxy.

### Claim 9 (depends on 1)

The compound of claim 1, wherein X is O or NR′.

### Claim 10 (depends on 1)

The compound of claim 1, wherein said compound has the structure:
wherein, unless otherwise indicated in the following table:
R2 and R3 taken together form an epoxide,
R6 is oxo, and R6′ is not present,
R12 is —OAc,
R20 is methyl,
R21 is hydrogen,
R25 is hydroxy,
R26 is oxo, and R26′ is not present,
R27 is methyl,
X is O, and
Compound
R1
R5
R7
R7′
R11
R15
Other
Taccalonolide AJ
—OAc
—H
—OH
—H
—OAc
—OH
Epoxytaccalonolide V
—OAc
—OH
—OAc
—H
—OAc
—OAc
R12 = —OH
Epoxytaccalonolide H
—OAc
—H
═O
Abs.
—OAc
—OAc
Epoxytaccalonolide
—OAc
Abs.
═O
Abs.
—OAc
—OAc
R6 = —OH,
AD
5,6Δ double
bond
Epoxytaccalonolide
—OAc
—H
—OH
—OH
—OAc
—OAc
AE
Epoxytaccalonolide
—OAc
—H
—OH
Abs.
—OAc
—OAc
7,8Δ double
H2
bond
Epoxy-TA-NaBH4-
—OAc
—H
—OH
—H
—OAc
—OH
R6 = —OAc,
12
R6′ = —H
Epoxy-TA-NaBH4-
—OAc
—H
—OH
—H
—OAc
—OH
R6 = —OH,
10
R6′ = —H
Epoxy-TB-Ac-16
—OAc
—H
—OAc
—H
—OAc
—OH
R25 = —OAc
Epoxytaccalonolide D
—OAc
—H
—OAc
—H
—OAc
—OH
Epoxytaccalonolide E
—OAc
—H
—OH
—H
—H
—OAc
Epoxytaccalonolide F
—OAc
—H
—OH
—H
—OH
—OAc
Epoxytaccalonolide L
—OAc
—H
—OH
—H
—OC(O)CH2OH
—OAc
Epoxytaccalonolide N
—OAc
—H
—OH
—H
—H
—OH
Epoxytaccalonolide G
—OAc
—OH
—OH
—H
—H
—H
Epoxytaccalonolide R
—OAc
—OH
—OAc
—H
—H
—OAc
Epoxytaccalonolide S
isobutyrate
—H
—OH
—H
—H
—OAc
Epoxytaccalonolide T
3-methyl
—OH
—OAc
—H
—H
—OAc
butanoate
Epoxytaccalonolide U
—OH
—OH
—OAc
—H
—H
—OAc
Epoxytaccalonolide Z
—OAc
—OH
—OH
—H
—OAc
—OAc
Epoxytaccalonolide
—OAc
—OH
—OAc
—H
—OAc
—OAc
AA
Epoxytaccalonolide
—OAc
—OH
—OH
—H
—OAc
—OH
AB
Epoxytaccalonolide
3-methyl
—OH
—OH
—H
—H
—OAc
AG
butanoate
Epoxytaccalonolide
3-methyl
—H
—OH
—H
—H
—OAc
AH
butanoate
Epoxytaccalonolide
3-methyl
—H
—OH
—H
—H
—OH
AI
butanoate
Epoxytaccalonolide I
—OAc
—H
═O
Abs.
—OAc
—OH
R6 = α-OH
Epoxytaccalonolide J
—OAc
—H
═O
Abs.
—OAc
—OAc
R6 = α-OH
Epoxytaccalonolide K
—OAc
—OH
═O
Abs.
—OAc
—OH
R6 = α-OH
Epoxytaccalonolide M
—OAc
—OH
═O
Abs.
—H
═O
R6 = α-OH
Epoxytaccalonolide W
—OAc
—H
—OH
—H
—OAc
—OH
R20 = OH
R21 = Me
Epoxytaccalonolide
—OAc
—H
—OH
—H
—OAc
—OAc
R20 = OOH
AC
R21 = Me

### Claim 11

A composition comprising at least 90% by weight of a compound of Formula I, wherein Formula I has the structure:
wherein:
R1 is hydrogen, amino, cyano, azido, halo, hydroxy, oxo, alkyl(C≦12), alkenyl(C≦12), alkoxy(C≦12), acyl(C≦12), acyloxy(C≦12), alkylamino(C≦12), dialkylamino(C≦12), amido(C≦12), alkylthio(C≦12), aryl(C≦12), aralkyl(C≦12), heterocycloalkyl(C≦12), or substituted versions thereof;
R2 is hydrogen, amino, cyano, azido, halo, hydroxy, oxo, alkyl(C≦12), alkenyl(C≦12), alkoxy(C≦12), acyl(C≦12), acyloxy(C≦12), alkylamino(C≦12), dialkylamino(C≦12), amido(C≦12), alkylthio(C≦12), aryl(C≦12), aralkyl(C≦12), heterocycloalkyl(C≦12), or substituted versions thereof, or R2 is taken together with R3 to form an epoxide at C-2/C-3;
R3 is hydrogen, amino, cyano, azido, halo, hydroxy, oxo, alkyl(C≦12), alkenyl(C≦12), alkoxy(C≦12), acyl(C≦12), acyloxy(C≦12), alkylamino(C≦12), dialkylamino(C≦12), amido(C≦12), alkylthio(C≦12), aryl(C≦12), aralkyl(C≦12), heterocycloalkyl(C≦12), and substituted versions thereof, or R3 is taken together with R2 as defined above;
R5 is absent, hydrogen, amino, cyano, azido, halo, hydroxy, alkyl(C≦12), alkenyl(C≦12), alkoxy(C≦12), acyl(C≦12), acyloxy(C≦12), alkylamino(C≦12), dialkylamino(C≦12), amido(C≦12), alkylthio(C≦12), aryl(C≦12), aralkyl(C≦12), heterocycloalkyl(C≦12), or substituted versions thereof;
R6 is hydrogen, amino, cyano, azido, halo, hydroxy, alkyl(C≦12), alkenyl(C≦12), alkoxy(C≦12), acyl(C≦12), acyloxy(C≦12), alkylamino(C≦12), dialkylamino(C≦12), amido(C≦12), alkylthio(C≦12), aryl(C≦12), aralkyl(C≦12), heterocycloalkyl(C≦12), or substituted versions thereof, or oxo if R6′ is not present, or R6 is taken together with R7 to form an epoxide at C-6/C-7;
R6′ when present is hydrogen, amino, cyano, azido, halo, hydroxy, alkenyl(C≦12), alkoxy(C≦12), acyl(C≦12), acyloxy(C≦12), alkylamino(C≦12), dialkylamino(C≦12), amido(C≦12), alkylthio(C≦12), aryl(C≦12), aralkyl(C≦12), heterocycloalkyl(C≦12), or substituted versions thereof;
R7 is hydrogen, amino, cyano, azido, halo, hydroxy, alkyl(C≦12), alkenyl(C≦12), alkoxy(C≦12), acyl(C≦12), acyloxy(C≦12), alkylamino(C≦12), dialkylamino(C≦12), amido(C≦12), alkylthio(C≦12), aryl(C≦12), aralkyl(C≦12), heterocycloalkyl(C≦12), or substituted versions thereof, or oxo if R7′ is not present, or R7 is taken together with R6 as defined above;
R7′ when present is hydrogen, amino, cyano, azido, halo, hydroxy, alkenyl(C≦12), alkoxy(C≦12), acyl(C≦12), acyloxy(C≦12), alkylamino(C≦12), dialkylamino(C≦12), amido(C≦12), alkylthio(C≦12), aryl(C≦12), aralkyl(C≦12), heterocycloalkyl(C≦12), or substituted versions thereof;
R11 is hydrogen, amino, cyano, azido, halo, hydroxy, alkyl(C≦12), alkenyl(C≦12), alkoxy(C≦12), acyl(C≦12), acyloxy(C≦12), alkylamino(C≦12), dialkylamino(C≦12), amido(C≦12), alkylthio(C≦12), aryl(C≦12), aralkyl(C≦12), heterocycloalkyl(C≦12), or substituted versions thereof;
R12 is hydrogen, amino, cyano, azido, halo, hydroxy, alkyl(C≦12), alkenyl(C≦12), alkoxy(C≦12), acyl(C≦12), acyloxy(C≦12), alkylamino(C≦12), dialkylamino(C≦12), amido(C≦12), alkylthio(C≦12), aryl(C≦12), aralkyl(C≦12), heterocycloalkyl(C≦12), or substituted versions thereof;
R15 is hydrogen, amino, cyano, azido, halo, hydroxy, oxo, alkyl(C≦12), alkenyl(C≦12), alkoxy(C≦12), acyl(C≦12), acyloxy(C≦12), alkylamino(C≦12), dialkylamino(C≦12), amido(C≦12), alkylthio(C≦12), aryl(C≦12), aralkyl(C≦12), heterocycloalkyl(C≦12), or substituted versions thereof,
R20 is hydrogen, amino, cyano, azido, halo, hydroxy, hydroperoxy, alkenyl(C≦12), alkoxy(C≦12), acyl(C≦12), acyloxy(C≦12), alkylamino(C≦12), dialkylamino(C≦12), amido(C≦12), alkylthio(C≦12), aryl(C≦12), aralkyl(C≦12), heterocycloalkyl(C≦12), or substituted versions thereof,
R21 is hydrogen, amino, cyano, azido, halo, hydroxy, alkyl(C≦12), alkenyl(C≦12), alkoxy(C≦12), acyl(C≦12), acyloxy(C≦12), alkylamino(C≦12), dialkylamino(C≦12), amido(C≦12), alkylthio(C≦12), aryl(C≦12), aralkyl(C≦12), heterocycloalkyl(C≦12), or substituted versions thereof,
R25 is hydrogen, amino, cyano, azido, halo, hydroxy, alkyl(C≦12), alkenyl(C≦12), alkoxy(C≦12), acyl(C≦12), acyloxy(C≦12), alkylamino(C≦12), dialkylamino(C≦12), amido(C≦12), alkylthio(C≦12), aryl(C≦12), aralkyl(C≦12), heterocycloalkyl(C≦12), or substituted versions thereof,
R26 is hydrogen, amino, cyano, azido, halo, hydroxy, alkyl(C≦12), alkenyl(C≦12), alkoxy(C≦12), acyl(C≦12), acyloxy(C≦12), alkylamino(C≦12), dialkylamino(C≦12), amido(C≦12), alkylthio(C≦12), aryl(C≦12), aralkyl(C≦12), heterocycloalkyl(C≦12), or substituted versions thereof, or oxo if R26′ is not present;
R26′ when present is hydrogen, amino, cyano, azido, halo, hydroxy, alkyl(C≦12), alkenyl(C≦12), alkoxy(C≦12), acyl(C≦12), acyloxy(C≦12), alkylamino(C≦12), dialkylamino(C≦12), amido(C≦12), alkylthio(C≦12), aryl(C≦12), aralkyl(C≦12), heterocycloalkyl(C≦12), or substituted versions thereof;
R27 is hydrogen, amino, cyano, azido, halo, hydroxy, alkyl(C≦12), alkenyl(C≦12), alkoxy(C≦12), acyl(C≦12), acyloxy(C≦12), alkylamino(C≦12), dialkylamino(C≦12), amido(C≦12), alkylthio(C≦12), aryl(C≦12), aralkyl(C≦12), heterocycloalkyl(C≦12), or substituted versions thereof; and
X is O, NR′ or CR′2, wherein each R′ is independently hydrogen or alkyl(C≦6);
or a pharmaceutically acceptable salt thereof,
wherein the —O— bridging C-22 and C-23 is optionally replaced with a double bond between C-22 and C-23.

### Claim 12

A composition comprising a compound of Formula I and a pharmaceutically acceptable carrier therefor, wherein Formula I has the structure:
wherein:
R1 is hydrogen, amino, cyano, azido, halo, hydroxy, oxo, alkyl(C≦12), alkenyl(C≦12), alkoxy(C≦12), acyl(C≦12), acyloxy(C≦12), alkylamino(C≦12), dialkylamino(C≦12), amido(C≦12), alkylthio(C≦12), aryl(C≦12), aralkyl(C≦12), heterocycloalkyl(C≦12), or substituted versions thereof;
R2 is hydrogen, amino, cyano, azido, halo, hydroxy, oxo, alkyl(C≦12), alkenyl(C≦12), alkoxy(C≦12), acyl(C≦12), acyloxy(C≦12), alkylamino(C≦12), dialkylamino(C≦12), amido(C≦12), alkylthio(C≦12), aryl(C≦12), aralkyl(C≦12), heterocycloalkyl(C≦12), or substituted versions thereof, or R2 is taken together with R3 to form an epoxide at C-2/C-3;
R3 is hydrogen, amino, cyano, azido, halo, hydroxy, oxo, alkyl(C≦12), alkenyl(C≦12), alkoxy(C≦12), acyl(C≦12), acyloxy(C≦12), alkylamino(C≦12), dialkylamino(C≦12), amido(C≦12), alkylthio(C≦12), aryl(C≦12), aralkyl(C≦12), heterocycloalkyl(C≦12), and substituted versions thereof, or R3 is taken together with R2 as defined above;
R5 is absent, hydrogen, amino, cyano, azido, halo, hydroxy, alkyl(C≦12), alkenyl(C≦12), alkoxy(C≦12), acyl(C≦12), acyloxy(C≦12), alkylamino(C≦12), dialkylamino(C≦12), amido(C≦12), alkylthio(C≦12), aryl(C≦12), aralkyl(C≦12), heterocycloalkyl(C≦12), or substituted versions thereof;
R6 is hydrogen, amino, cyano, azido, halo, hydroxy, alkyl(C≦12), alkenyl(C≦12), alkoxy(C≦12), acyl(C≦12), acyloxy(C≦12), alkylamino(C≦12), dialkylamino(C≦12), amido(C≦12), alkylthio(C≦12), aryl(C≦12), aralkyl(C≦12), heterocycloalkyl(C≦12), or substituted versions thereof, or oxo if R6′ is not present, or R6 is taken together with R7 to form an epoxide at C-6/C-7;
R6′ when present is hydrogen, amino, cyano, azido, halo, hydroxy, alkenyl(C≦12), alkoxy(C≦12), acyl(C≦12), acyloxy(C≦12), alkylamino(C≦12), dialkylamino(C≦12), amido(C≦12), alkylthio(C≦12), aryl(C≦12), aralkyl(C≦12), heterocycloalkyl(C≦12), or substituted versions thereof;
R7 is hydrogen, amino, cyano, azido, halo, hydroxy, alkyl(C≦12), alkenyl(C≦12), alkoxy(C≦12), acyl(C≦12), acyloxy(C≦12), alkylamino(C≦12), dialkylamino(C≦12), amido(C≦12), alkylthio(C≦12), aryl(C≦12), aralkyl(C≦12), heterocycloalkyl(C≦12), or substituted versions thereof, or oxo if R7′ is not present, or R7 is taken together with R6 as defined above;
R7′ when present is hydrogen, amino, cyano, azido, halo, hydroxy, alkyl(C≦12), alkenyl(C≦12), alkoxy(C≦12), acyl(C≦12), acyloxy(C≦12), alkylamino(C≦12), dialkylamino(C≦12), amido(C≦12), alkylthio(C≦12), aryl(C≦12), aralkyl(C≦12), heterocycloalkyl(C≦12), or substituted versions thereof;
R11 is hydrogen, amino, cyano, azido, halo, hydroxy, alkyl(C≦12), alkenyl(C≦12), alkoxy(C≦12), acyl(C≦12), acyloxy(C≦12), alkylamino(C≦12), dialkylamino(C≦12), amido(C≦12), alkylthio(C≦12), aryl(C≦12), aralkyl(C≦12), heterocycloalkyl(C≦12), or substituted versions thereof,
R12 is hydrogen, amino, cyano, azido, halo, hydroxy, alkyl(C≦12), alkenyl(C≦12), alkoxy(C≦12), acyl(C≦12), acyloxy(C≦12), alkylamino(C≦12), dialkylamino(C≦12), amido(C≦12), alkylthio(C≦12), aryl(C≦12), aralkyl(C≦12), heterocycloalkyl(C≦12), or substituted versions thereof,
R15 is hydrogen, amino, cyano, azido, halo, hydroxy, oxo, alkyl(C≦12), alkenyl(C≦12), alkoxy(C≦12), acyl(C≦12), acyloxy(C≦12), alkylamino(C≦12), dialkylamino(C≦12), amido(C≦12), alkylthio(C≦12), aryl(C≦12), aralkyl(C≦12), heterocycloalkyl(C≦12), or substituted versions thereof,
R20 is hydrogen, amino, cyano, azido, halo, hydroxy, hydroperoxy, alkenyl(C≦12), alkoxy(C≦12), acyl(C≦12), acyloxy(C≦12), alkylamino(C≦12), dialkylamino(C≦12), amido(C≦12), alkylthio(C≦12), aryl(C≦12), aralkyl(C≦12), heterocycloalkyl(C≦12), or substituted versions thereof,
R21 is hydrogen, amino, cyano, azido, halo, hydroxy, alkyl(C≦12), alkenyl(C≦12), alkoxy(C≦12), acyl(C≦12), acyloxy(C≦12), alkylamino(C≦12), dialkylamino(C≦12), amido(C≦12), alkylthio(C≦12), aryl(C≦12), aralkyl(C≦12), heterocycloalkyl(C≦12), or substituted versions thereof,
R25 is hydrogen, amino, cyano, azido, halo, hydroxy, alkyl(C≦12), alkenyl(C≦12), alkoxy(C≦12), acyl(C≦12), acyloxy(C≦12), alkylamino(C≦12), dialkylamino(C≦12), amido(C≦12), alkylthio(C≦12), aryl(C≦12), aralkyl(C≦12), heterocycloalkyl(C≦12), or substituted versions thereof,
R26 is hydrogen, amino, cyano, azido, halo, hydroxy, alkyl(C≦12), alkenyl(C≦12), alkoxy(C≦12), acyl(C≦12), acyloxy(C≦12), alkylamino(C≦12), dialkylamino(C≦12), amido(C≦12), alkylthio(C≦12), aryl(C≦12), aralkyl(C≦12), heterocycloalkyl(C≦12), or substituted versions thereof, or oxo if R26′ is not present;
R26′ when present is hydrogen, amino, cyano, azido, halo, hydroxy, alkenyl(C≦12), alkoxy(C≦12), acyl(C≦12), acyloxy(C≦12), alkylamino(C≦12), dialkylamino(C≦12), amido(C≦12), alkylthio(C≦12), aryl(C≦12), aralkyl(C≦12), heterocycloalkyl(C≦12), or substituted versions thereof;
R27 is hydrogen, amino, cyano, azido, halo, hydroxy, alkyl(C≦12), alkenyl(C≦12), alkoxy(C≦12), acyl(C≦12), acyloxy(C≦12), alkylamino(C≦12), dialkylamino(C≦12), amido(C≦12), alkylthio(C≦12), aryl(C≦12), aralkyl(C≦12), heterocycloalkyl(C≦12), or substituted versions thereof; and
X is O, NR′ or CR′2, wherein each R′ is independently hydrogen or alkyl(C≦6);
or a pharmaceutically acceptable salt thereof,
wherein the —O— bridging C-22 and C-23 is optionally replaced with a double bond between C-22 and C-23.

### Claim 13 (depends on 12)

The composition of claim 12, wherein, unless otherwise indicated in the following table, the compound is selected from the group consisting of compounds having the structure:
the —O— bridging C-22 and C-23 is optionally replaced with a double bond between C-22 and C-23;
R2 and R3 taken together form an epoxide,
R6 is oxo, and R6′ is not present,
R12 is —OAc,
R20 is methyl,
R21 is hydrogen,
R25 is hydroxy,
R26 is oxo, and R26′ is not present,
R27 is methyl,
X is O, and
Compound
R1
R5
R7
R7′
R11
R15
Other
Taccalonolide AI
3-methyl
—H
—OH
—H
—H
—OH
butanoate
Taccalonolide AA
—OAc
—OH
—OAc
—H
—OAc
—OAc
Taccalonolide Z
—OAc
—OH
—OH
—H
—OAc
—OAc
Taccalonolide AB
—OAc
—OH
—OH
—H
—OAc
—OH
Taccalonolide AC
—OAc
—H
—OH
—H
—OAc
—OAc
R20 = OOH
R21 = Me
Taccalonolide AD
—OAc
Abs.
═O
Abs.
—OAc
—OAc
R6 = OH,
5,6Δ double bond
Taccalonolide AE
—OAc
—H
—OH
—OH
—OAc
—OAc
Taccalonolide AG
3-methyl
—OH
—OH
—H
—H
—OAc
butanoate
Taccalonolide AH
3-methyl
—H
—OH
—H
—H
—OAc
butanoate
Taccalonolide H2
—OAc
—H
—OH
Abs.
—OAc
—OAc
7,8Δ double bond
TA-NaBH4-12
—OAc
—H
—OH
—H
—OAc
—OH
R6 = —OAc,
R6′ = —H
TA-NaBH4-10
—OAc
—H
—OH
—H
—OAc
—OH
R6 = —OH,
R6′ = —H
TB-Ac-16
—OAc
—H
—OAc
—H
—OAc
—OH
R25 = —OAc
Taccalonolide AL
—OAc
—OH
—OH
—H
—H
—OH
Taccalonolide AM
3-methyl
—OH
—OH
—H
—H
—OH
butanoate
Taccalonolide AN
—OH
—H
—OH
—H
—H
—OH
Taccalonolide AP
—OAc
—OH
—OH
—H
—H
—OAc
Taccalonolide AQ
—OH
—OH
—OH
—H
—OAc
—OAc
R2 = —OAc
R3 = —Cl

### Claim 14 (depends on 12)

The composition of claim 12, wherein said compound is selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.

### Claim 15 (depends on 1)

A method of treating a hyperproliferative disorder in a patient, the method comprising administering to a patient in need thereof an effective amount of a compound of claim 1.

### Claim 16 (depends on 13)

A method of treating a hyperproliferative disorder in a patient, the method comprising administering to a patient in need thereof an effective amount of a composition of claim 13.

### Claim 17 (depends on 1)

Use of a compound according to claim 1 in the preparation of a medicament for the treatment of a hyperproliferative disorder in a patient.

### Claim 18 (depends on 13)

Use of a composition according to claim 13 in the preparation of a medicament for the treatment of a hyperproliferative disorder in a patient.

### Claim 19 (depends on 1)

A compound according to claim 1 for the treatment of a hyperproliferative disorder in a patient.

### Claim 20

A method of producing a mixture of epoxytaccalonolides, said method comprising subjecting a solution of a taccalonolide-containing crude extract of the roots and/or rhizomes of a Tacca species in an organic solvent to epoxidation.