# US 2014/0194495 A1 · Cytotoxin compounds and methods of isolation > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2014/0194495 A1 - Document ID: US20140194495A1 - Status: Published application - Kind: A1 - Application number: 14/204,996 - Filed: 2014-03-11 - Published: 2014-07-10 - Earliest claimed: 2004-02-17 - Assignees: The UAB Research Foundation; University of South Florida - Applicants: The Uab Research Foundation; University of South Florida - Inventors: BILL J. BAKER; THUSHARA DIYABALANAGE; JAMES B. MCCLINTOCK; CHARLES D. AMSLER - Web page: https://patentgrep.com/patent/US20140194495A1 ## CPC - C07D 313/00: Heterocyclic compounds containing rings of more than six members having one oxygen atom as the only ring hetero atom - A61K 31/365: Lactones - A61P 35/00: Antineoplastic agents - C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08) - 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 ## Abstract The present invention concerns groups of compounds derived from tunicates of the Synoicum species, as well as to pharmaceutical compositions comprising these compounds, and uses thereof. Extracts from tunicates show selective toxicity against several different cancer cell lines in the NCI 60 cell line panel. These compounds are useful in the effective treatment of cancers, particularly malignant melanomas, colon cancer, and renal cancer cell lines. ## Claims ### Claim at position 1 1-26. (canceled) ### Claim 27 An isolated Palmerolide compound of any of formula I or II, or a composition comprising a Palmerolide compound of any of formula I or II: wherein: =single or double bond R1 is carboxaldehyde, —CHCHNHC(O)-Alkyl, —OC-Alkyl, —OC-aryl, —OC-amino, aryl, amino, -vinylamido, arylamido, alkyl, alkoxy, cycloalkyl, cycloalkoxy, aryloxy, alkylcarbonyl; alkoxycarbonyl, cycloalkylcarbonyl, cycloalkoxycarbonyl, heteroalkyl, heterocycloalkyl, heteroaryl, arylcarbonyl, heteroarycarbonyl, heterocycloalkylcarbonyl, aryloxycarbonyl, heteroaryloxycarbony, heterocycloalkoxycarbonyl, a halogen, or —CHO, any of which can be optionally substituted with H, alkyl, alkoxy, —OH, —NO2, —NH2, —COOH, a halogen, or —CH3; R2 is, independently, OH, O-Acyl, carbamate, H, O-alkyl, amino, —OSO3H, alkyl, alkoxy, cycloalkyl, cycloalkoxy, aryloxy, alkylcarbonyl; alkoxycarbonyl, cycloalkylcarbonyl, cycloalkoxycarbonyl, heteroalkyl, heterocycloalkyl, heteroaryl, aryl carbonyl, heteroarycarbonyl, heterocycloalkylcarbonyl, aryloxycarbonyl, heteroaryloxycarbony, heterocycloalkoxycarbonyl, a halogen, and/or oxo; R3 is H, alkyl, alkoxy, cycloalkyl, cycloalkoxy, aryloxy, alkylcarbonyl; alkoxycarbonyl, cycloalkylcarbonyl, cycloalkoxycarbonyl, heteroalkyl, heterocycloalkyl, heteroaryl, arylcarbonyl, heteroarycarbonyl, heterocycloalkylcarbonyl, aryloxycarbonyl, heteroaryloxycarbony, heterocycloalkoxycarbonyl, halogen, any of which can be optionally substituted with alkyl, alkoxy, —OH, —NO2, —NH2, —COOH, a halogen, and/or —CH3; R4 is, independently, H, alkyl, alkoxy, cycloalkyl, cycloalkoxy, aryloxy, alkylcarbonyl; alkoxycarbonyl, cycloalkylcarbonyl, cycloalkoxycarbonyl, heteroalkyl, heterocycloalkyl, heteroaryl, arylcarbonyl, heteroarycarbonyl, heterocycloalkylcarbonyl, aryloxycarbonyl, heteroaryloxycarbony, heterocycloalkoxycarbonyl, halogen, any of which can be optionally substituted with alkyl, alkoxy, —OH, —NO2, —NH2, —COOH, a halogen, and/or —CH3; and isomers, racemates or racemic mixtures thereof, and pharmaceutically acceptable salts or crystalline forms thereof. ### Claim 28 (depends on 27) The Palmerolide compound according to claim 27, wherein at least one R2 is —OC(NH2)O. ### Claim 29 (depends on 27) The Palmerolide compound according to claim 27, wherein R3 is methyl. ### Claim 30 (depends on 27) The Palmerolide compound according to claim 27, wherein at least one R4 is methyl. ### Claim 31 (depends on 27) The Palmerolide compound according to claim 27, wherein both R4 are methyl. ### Claim 32 (depends on 27) The Palmerolide compound according to claim 27, wherein R1 is —CHCHNHC(O)CHC(CH3)2. ### Claim 33 (depends on 27) The Palmerolide compound according to claim 27, wherein R1 is —CHCHNHC(O)CHC(CH3)CH2C(CH3)CH2. ### Claim 34 (depends on 27) The Palmerolide compound according to claim 27, wherein R1 is —CHCHNHC(O)CHC(CH3)CH2C(CH3)CH2. ### Claim 35 (depends on 27) The Palmerolide compound according to claim 27, wherein R1 is —CH═O. ### Claim 36 (depends on 27) The Palmerolide compound according to claim 27, wherein at least one R2 is —OH. ### Claim 37 (depends on 27) The Palmerolide compound according to claim 27, wherein at least one R2 is —OSO3H. ### Claim 38 (depends on 27) The Palmerolide compound according to claim 27, wherein at least two R2 are —OH and at least one R2 is —OC(NH2)O, and optionally R3 and R4 are —CH3. ### Claim 39 A method for inhibiting a V-ATPase enzyme, said method comprising contacting or exposing said V-ATPase enzyme to an amount of a Palmerolide compound of any of formula I or a composition comprising a Palmerolide compound of any of formula I: wherein: =single or double bond R1 is carboxaldehyde, —CHCHNHC(O)-Alkyl, —OC-Alkyl, —OC-aryl, —OC-amino, aryl, amino, -vinylamido, arylamido, alkyl, alkoxy, cycloalkyl, cycloalkoxy, aryloxy, alkylcarbonyl; alkoxycarbonyl, cycloalkylcarbonyl, cycloalkoxycarbonyl, heteroalkyl, heterocycloalkyl, heteroaryl, arylcarbonyl, heteroarycarbonyl, heterocycloalkylcarbonyl, aryloxycarbonyl, heteroaryloxycarbony, heterocycloalkoxycarbonyl, a halogen, or —CHO, any of which can be optionally substituted with H, alkyl, alkoxy, —OH, —NO2, —NH2, —COOH, a halogen, or —CH3; R2 is, independently, OH, O-Acyl, carbamate, H, O-alkyl, amino, —OSO3H, alkyl, alkoxy, cycloalkyl, cycloalkoxy, aryloxy, alkylcarbonyl; alkoxycarbonyl, cycloalkylcarbonyl, cycloalkoxycarbonyl, heteroalkyl, heterocycloalkyl, heteroaryl, arylcarbonyl, heteroarycarbonyl, heterocycloalkylcarbonyl, aryloxycarbonyl, heteroaryloxycarbony, heterocycloalkoxycarbonyl, a halogen, and/or oxo; R3 is H, alkyl, alkoxy, cycloalkyl, cycloalkoxy, aryloxy, alkylcarbonyl; alkoxycarbonyl, cycloalkyl carbonyl, cycloalkoxycarbonyl, heteroalkyl, heterocycloalkyl, heteroaryl, arylcarbonyl, heteroarycarbonyl, heterocycloalkylcarbonyl, aryloxycarbonyl, heteroaryloxycarbony, heterocycloalkoxycarbonyl, halogen, any of which can be optionally substituted with alkyl, alkoxy, —OH, —NO2, —NH2, —COOH, a halogen, and/or —CH3; R4 is, independently, H, alkyl, alkoxy, cycloalkyl, cycloalkoxy, aryloxy, alkylcarbonyl; alkoxycarbonyl, cycloalkylcarbonyl, cycloalkoxycarbonyl, heteroalkyl, heterocycloalkyl, heteroaryl, arylcarbonyl, heteroarycarbonyl, heterocycloalkylcarbonyl, aryloxycarbonyl, heteroaryloxycarbony, heterocycloalkoxycarbonyl, halogen, any of which can be optionally substituted with alkyl, alkoxy, —OH, —NO2, —NH2, —COOH, a halogen, and/or —CH3; and isomers, racemates or racemic mixtures thereof, and pharmaceutically acceptable salts or crystalline forms thereof; or a Palmerolide compound of any of formula II or a composition comprising a Palmerolide compound of any of formula II: wherein: =single or double bond R1 is carboxaldehyde, —CHCHNHC(O)-Alkyl, —OC-Alkyl, —OC-aryl, —OC-amino, aryl, amino, -vinylamido, arylamido, alkyl, alkoxy, cycloalkyl, cycloalkoxy, aryloxy, alkylcarbonyl; alkoxycarbonyl, cycloalkylcarbonyl, cycloalkoxycarbonyl, heteroalkyl, heterocycloalkyl, heteroaryl, arylcarbonyl, heteroarycarbonyl, heterocycloalkylcarbonyl, aryloxycarbonyl, heteroaryloxycarbony, heterocycloalkoxycarbonyl, a halogen, or —CHO, any of which can be optionally substituted with H, alkyl, alkoxy, —OH, —NO2, —NH2, —COOH, a halogen, or —CH3; R2 is, independently, OH, O-Acyl, carbamate, H, O-alkyl, amino, —OSO3H, alkyl, alkoxy, cycloalkyl, cycloalkoxy, aryloxy, alkylcarbonyl; alkoxycarbonyl, cycloalkylcarbonyl, cycloalkoxycarbonyl, heteroalkyl, heterocycloalkyl, heteroaryl, arylcarbonyl, heteroarycarbonyl, heterocycloalkylcarbonyl, aryloxycarbonyl, heteroaryloxycarbony, heterocycloalkoxycarbonyl, a halogen, and/or oxo; R3 is H, alkyl, alkoxy, cycloalkyl, cycloalkoxy, aryloxy, alkylcarbonyl; alkoxycarbonyl, cycloalkylcarbonyl, cycloalkoxycarbonyl, heteroalkyl, heterocycloalkyl, heteroaryl, arylcarbonyl, heteroarycarbonyl, heterocycloalkylcarbonyl, aryloxycarbonyl, heteroaryloxycarbony, heterocycloalkoxycarbonyl, halogen, any of which can be optionally substituted with alkyl, alkoxy, —OH, —NO2, —NH2, —COOH, a halogen, and/or —CH3; R4 is, independently, H, alkyl, alkoxy, cycloalkyl, cycloalkoxy, aryloxy, alkylcarbonyl; alkoxycarbonyl, cycloalkylcarbonyl, cycloalkoxycarbonyl, heteroalkyl, heterocycloalkyl, heteroaryl, arylcarbonyl, heteroarycarbonyl, heterocycloalkylcarbonyl, aryloxycarbonyl, heteroaryloxycarbony, heterocycloalkoxycarbonyl, halogen, any of which can be optionally substituted with alkyl, alkoxy, —OH, —NO2, —NH2, —COOH, a halogen, and/or —CH3; and isomers, racemates or racemic mixtures thereof, and pharmaceutically acceptable salts or crystalline forms thereof; and wherein said Palmerolide compound is effective to inhibit activity or block function of said V-ATPase. ### Claim 40 A method for treating a condition associated with expression of a V-ATPase enzyme, said method comprising administering to a person or animal in need of treatment of an effective amount of a Palmerolide compound of any of formula I or a composition comprising a Palmerolide compound of any of formula I: wherein: =single or double bond R1 is carboxaldehyde, —CHCHNHC(O)-Alkyl, —OC-Alkyl, —OC-aryl, —OC-amino, aryl, amino, -vinylamido, arylamido, alkyl, alkoxy, cycloalkyl, cycloalkoxy, aryloxy, alkylcarbonyl; alkoxycarbonyl, cycloalkylcarbonyl, cycloalkoxycarbonyl, heteroalkyl, heterocycloalkyl, heteroaryl, arylcarbonyl, heteroarycarbonyl, heterocycloalkylcarbonyl, aryloxycarbonyl, heteroaryloxycarbony, heterocycloalkoxycarbonyl, a halogen, or —CHO, any of which can be optionally substituted with H, alkyl, alkoxy, —OH, —NO2, —NH2, —COOH, a halogen, or —CH3; R2 is, independently, OH, O-Acyl, carbamate, H, O-alkyl, amino, —OSO3H, alkyl, alkoxy, cycloalkyl, cycloalkoxy, aryloxy, alkylcarbonyl; alkoxycarbonyl, cycloalkylcarbonyl, cycloalkoxycarbonyl, heteroalkyl, heterocycloalkyl, heteroaryl, arylcarbonyl, heteroarycarbonyl, heterocycloalkylcarbonyl, aryloxycarbonyl, heteroaryloxycarbony, heterocycloalkoxycarbonyl, a halogen, and/or oxo; R3 is H, alkyl, alkoxy, cycloalkyl, cycloalkoxy, aryloxy, alkylcarbonyl; alkoxycarbonyl, cycloalkyl carbonyl, cycloalkoxycarbonyl, heteroalkyl, heterocycloalkyl, heteroaryl, arylcarbonyl, heteroarycarbonyl, heterocycloalkylcarbonyl, aryloxycarbonyl, heteroaryloxycarbony, heterocycloalkoxycarbonyl, halogen, any of which can be optionally substituted with alkyl, alkoxy, —OH, —NO2, —NH2, —COOH, a halogen, and/or —CH3; R4 is, independently, H, alkyl, alkoxy, cycloalkyl, cycloalkoxy, aryloxy, alkylcarbonyl; alkoxycarbonyl, cycloalkylcarbonyl, cycloalkoxycarbonyl, heteroalkyl, heterocycloalkyl, heteroaryl, arylcarbonyl, heteroarycarbonyl, heterocycloalkylcarbonyl, aryloxycarbonyl, heteroaryloxycarbony, hetcrocycloalkoxycarbonyl, halogen, any of which can be optionally substituted with alkyl, alkoxy, —OH, —NO2, —NH2, —COOK a halogen, and/or —CH3; and isomers, racemates or racemic mixtures thereof, and pharmaceutically acceptable salts or crystalline forms thereof; or a Palmerolide compound of any of formula II or a composition comprising a Palmerolide compound of any of formula II: wherein: =single or double bond R1 is carboxaldehyde, —CHCHNHC(O)-Alkyl, —OC-Alkyl, —OC-aryl, —OC-amino, aryl, amino, -vinylamido, arylamido, alkyl, alkoxy, cycloalkyl, cycloalkoxy, aryloxy, alkylcarbonyl; alkoxycarbonyl, cycloalkylcarbonyl, cycloalkoxycarbonyl, heteroalkyl, heterocycloalkyl, heteroaryl, arylcarbonyl, heteroarycarbonyl, heterocycloalkylcarbonyl, aryloxycarbonyl, heteroaryloxycarbony, heterocycloalkoxycarbonyl, a halogen, or —CHO, any of which can be optionally substituted with H, alkyl, alkoxy, —OH, —NO2, —NH2, —COOH, a halogen, or —CH3; R2 is, independently, OH, O-Acyl, carbamate, H, O-alkyl, amino, —OSO3H, alkyl, alkoxy, cycloalkyl, cycloalkoxy, aryloxy, alkylcarbonyl; alkoxycarbonyl, cycloalkylcarbonyl, cycloalkoxycarbonyl, heteroalkyl, heterocycloalkyl, heteroaryl, arylcarbonyl, heteroarycarbonyl, heterocycloalkylcarbonyl, aryloxycarbonyl, heteroaryloxycarbony, heterocycloalkoxycarbonyl, a halogen, and/or oxo; R3 is H, alkyl, alkoxy, cycloalkyl, cycloalkoxy, aryloxy, alkylcarbonyl; alkoxycarbonyl, cycloalkylcarbonyl, cycloalkoxycarbonyl, heteroalkyl, heterocycloalkyl, heteroaryl, arylcarbonyl, heteroarycarbonyl, heterocycloalkylcarbonyl, aryloxycarbonyl, heteroaryloxycarbony, heterocycloalkoxycarbonyl, halogen, any of which can be optionally substituted with alkyl, alkoxy, —OH, —NO2, —NH2, —COOH, a halogen, and/or —CH3; R4 is, independently, H, alkyl, alkoxy, cycloalkyl, cycloalkoxy, aryloxy, alkylcarbonyl; alkoxycarbonyl, cycloalkylcarbonyl, cycloalkoxycarbonyl, heteroalkyl, heterocycloalkyl, heteroaryl, arylcarbonyl, heteroarycarbonyl, heterocycloalkylcarbonyl, aryloxycarbonyl, heteroaryloxycarbony, heterocycloalkoxycarbonyl, halogen, any of which can be optionally substituted with alkyl, alkoxy, —OH, —NO2, —COOH, a halogen, and/or —CH3; and isomers, racemates or racemic mixtures thereof, and pharmaceutically acceptable salts or crystalline forms thereof. ### Claim 41 A method for treating a person or animal having a cancerous or oncological disorder, said method comprising administering to said person or animal a therapeutically effective amount of a Palmerolide compound of any of formula I or a composition comprising a Palmerolide compound of any of formula I: wherein: =single or double bond R1 is carboxaldehyde, —CHCHNHC(O)-Alkyl, —OC-Alkyl, —OC-aryl, —OC-amino, aryl, amino, -vinylamido, arylamido, alkyl, alkoxy, cycloalkyl, cycloalkoxy, aryloxy, alkylcarbonyl; alkoxycarbonyl, cycloalkylcarbonyl, cycloalkoxycarbonyl, heteroalkyl, heterocycloalkyl, heteroaryl, arylcarbonyl, heteroarycarbonyl, heterocycloalkylcarbonyl, aryloxycarbonyl, heteroaryloxycarbony, heterocycloalkoxycarbonyl, a halogen, or —CHO, any of which can be optionally substituted with H, alkyl, alkoxy, —OH, —NO2, —NH2, —COOH, a halogen, or —CH3; R2 is, independently, OH, O-Acyl, carbamate, H, O-alkyl, amino, —OSO3H, alkyl, alkoxy, cycloalkyl, cycloalkoxy, aryloxy, alkylcarbonyl; alkoxycarbonyl, cycloalkylcarbonyl, cycloalkoxycarbonyl, heteroalkyl, heterocycloalkyl, heteroaryl, arylcarbonyl, hetcroarycarbonyl, heterocycloalkylcarbonyl, aryl oxycarbonyl, heteroaryloxycarbony, heterocycloalkoxycarbonyl, a halogen, and/or oxo; R3 is II, alkyl, alkoxy, cycloalkyl, cycloalkoxy, aryloxy, alkylcarbonyl; alkoxycarbonyl, cycloalkylcarbonyl, cycloalkoxycarbonyl, heteroalkyl, heterocycloalkyl, heteroaryl, arylcarbonyl, heteroarycarbonyl, heterocycloalkylcarbonyl, aryloxycarbonyl, heteroaryloxycarbony, heterocycloalkoxycarbonyl, halogen, any of which can be optionally substituted with alkyl, alkoxy, —OH, —NO2, —H2, —COOH, a halogen, and/or —CH3; R4 is, independently, H, alkyl, alkoxy, cycloalkyl, cycloalkoxy, aryloxy, alkylcarbonyl; alkoxycarbonyl, cycloalkylcarbonyl, cycloalkoxycarbonyl, heteroalkyl, heterocycloalkyl, heteroaryl, arylcarbonyl, heteroarycarbonyl, heterocycloalkylcarbonyl, aryloxycarbonyl, heteroaryloxycarbony, heterocycloalkoxycarbonyl, halogen, any of which can be optionally substituted with alkyl, alkoxy, —OH, —NO2, —NH2, —COOH, a halogen, and/or —CH3; and isomers, racemates or racemic mixtures thereof, and pharmaceutically acceptable salts or crystalline forms thereof; or a Palmerolide compound of any of formula II or a composition comprising a Palmerolide compound of any of formula II: wherein: =single or double bond R1 is carboxaldehyde, —CHCHNHC(O)-Alkyl, —OC-Alkyl, —OC-aryl, —OC-amino, aryl, amino, -vinylamido, arylamido, alkyl, alkoxy, cycloalkyl, cycloalkoxy, aryloxy, alkylcarbonyl; alkoxycarbonyl, cycloalkylcarbonyl, cycloalkoxycarbonyl, heteroalkyl, heterocycloalkyl, heteroaryl, arylcarbonyl, heteroarycarbonyl, heterocycloalkylcarbonyl, aryloxycarbonyl, heteroaryloxycarbony, heterocycloalkoxycarbonyl, a halogen, or —CHO, any of which can be optionally substituted with H, alkyl, alkoxy, —OH, —NO2, —NH2, —COOH, a halogen, or —CH3; R2 is, independently, OH, O-Acyl, carbamate, H, O-alkyl, amino, —OSO3H, alkyl, alkoxy, cycloalkyl, cycloalkoxy, aryloxy, alkylcarbonyl; alkoxycarbonyl, cycloalkylcarbonyl, cycloalkoxycarbonyl, heteroalkyl, heterocycloalkyl, heteroaryl, arylcarbonyl, heteroarycarbonyl, heterocycloalkylcarbonyl, aryloxycarbonyl, heteroaryloxycarbony, heterocycloalkoxycarbonyl, a halogen, and/or oxo; R3 is H, alkyl, alkoxy, cycloalkyl, cycloalkoxy, aryloxy, alkylcarbonyl; alkoxycarbonyl, cycloalkylcarbonyl, cycloalkoxycarbonyl, heteroalkyl, heterocycloalkyl, heteroaryl, arylcarbonyl, heteroarycarbonyl, heterocycloalkylcarbonyl, aryloxycarbonyl, heteroaryloxycarbony, heterocycloalkoxycarbonyl, halogen, any of which can be optionally substituted with alkyl, alkoxy, —OH, —NO2, —NH2, —COOH, a halogen, and/or —CH3; R4 is, independently, H, alkyl, alkoxy, cycloalkyl, cycloalkoxy, aryloxy, alkylcarbonyl; alkoxycarbonyl, cycloalkylcarbonyl, cycloalkoxycarbonyl, heteroalkyl, heterocycloalkyl, heteroaryl, arylcarbonyl, heteroarycarbonyl, heterocycloalkylcarbonyl, aryloxycarbonyl, heteroaryloxycarbony, heterocycloalkoxycarbonyl, halogen, any of which can be optionally substituted with alkyl, alkoxy, —OH, —NO2, —NH2, —COOH, a halogen, and/or —CH3; and isomers, racemates or racemic mixtures thereof, and pharmaceutically acceptable salts or crystalline forms thereof. ### Claim 42 A method for isolating a Palmerolide, said method comprising: a) subjecting a Synoicum tunicate to solvent extraction; b) removing said solvent to provide an extract; and c) fractionating said extract to isolate said Palmerolide. ### Claim 43 (depends on 42) The method according to claim 42, wherein said solvent is CH2CH2/MeOH. ### Claim 44 (depends on 42) The method according to claim 42, wherein said extract is fractionated using flash chromatography. ### Claim 45 (depends on 44) The method according to claim 44, wherein said flash chromatography is gradient flash chromatography over silica. ### Claim 46 (depends on 42) The method according to claim 42, wherein fractions obtained following said fractionating in step (c) are subjected to gradient elution over silica gel. ### Claim 47 (depends on 42) The method according to claim 42, wherein fractions obtained following said fractionating in step (c) are subjected to high performance liquid chromatography (HPLC), such as reverse phase HPLC. ### Claim 48 (depends on 42) The method according to claim 42, wherein said solvent is removed by evaporation. ### Claim 49 (depends on 42) The method according to claim 42, wherein after step (b), said extract is partitioned in a solvent. ### Claim 50 (depends on 49) The method according to claim 49, wherein said solvent is ethyl acetate. ### Claim 51 (depends on 49) The method according to claim 49, wherein said solvent partitioned extract is washed and dried. ### Claim 52 (depends on 42) The method according to claim 42, wherein said method further comprises obtaining said tunicates. ### Claim 53 (depends on 42) The method according to claim 42, wherein said tunicate is Synoicum adareanum. ### Claim 54 (depends on 42) The method according to claim 42, wherein said tunicate is freeze-dried. ### Claim 55 (depends on 42) The method according to claim 42, wherein the Palmerolide is Palmerolide A, Palmerolide B, Palmerolide C, Palmerolide D, Palmerolide E, Palmerolide F, Palmerolide G, Palmerolide H, or Palmerolide K. ### Claim 56 A kit comprising in one or more containers a Palmerolide compound of any of formula I or a composition comprising a Palmerolide compound of any of formula I: wherein: =single or double bond R1 is carboxaldehyde, —CHCHNHC(O)-Alkyl, —OC-Alkyl, —OC-aryl, —OC-amino, aryl, amino, -vinylamido, arylamido, alkyl, alkoxy, cycloalkyl, cycloalkoxy, aryloxy, alkylcarbonyl; alkoxycarbonyl, cycloalkylcarbonyl, cycloalkoxycarbonyl, heteroalkyl, heterocycloalkyl, heteroaryl, arylcarbonyl, heteroarycarbonyl, heterocycloalkylcarbonyl, aryloxycarbonyl, heteroaryloxycarbony, heterocycloalkoxycarbonyl, a halogen, or —CHO, any of which can be optionally substituted with H, alkyl, alkoxy, —OH, —NO2, —NH2, —COOH, a halogen, or —CH3; R2 is, independently, OH, O-Acyl, carbamate, H, O-alkyl, amino, —OSO3H, alkyl, alkoxy, cycloalkyl, cycloalkoxy, aryloxy, alkylcarbonyl; alkoxycarbonyl, cycloalkylcarbonyl, cycloalkoxycarbonyl, heteroalkyl, heterocycloalkyl, heteroaryl, arylcarbonyl, heteroarycarbonyl, heterocycloalkylcarbonyl, aryloxycarbonyl, heteroaryloxycarbony, heterocycloalkoxycarbonyl, a halogen, and/or oxo; R3 is H, alkyl, alkoxy, cycloalkyl, cycloalkoxy, aryloxy, alkylcarbonyl; alkoxycarbonyl, cycloalkylcarbonyl, cycloalkoxycarbonyl, heteroalkyl, heterocycloalkyl, heteroaryl, arylcarbonyl, heteroarycarbonyl, heterocycloalkylcarbonyl, aryloxycarbonyl, heteroaryloxycarbony, heterocycloalkoxycarbonyl, halogen, any of which can be optionally substituted with alkyl, alkoxy, —OH, —NO2, —NH2, —COOH, a halogen, and/or —CH3; R4 is, independently, H, alkyl, alkoxy, cycloalkyl, cycloalkoxy, aryloxy, alkylcarbonyl; alkoxycarbonyl, cycloalkylcarbonyl, cycloalkoxycarbonyl, heteroalkyl, heterocycloalkyl, heteroaryl, arylcarbonyl, heteroarycarbonyl, heterocycloalkylcarbonyl, aryloxycarbonyl, heteroaryloxycarbony, heterocycloalkoxycarbonyl, halogen, any of which can be optionally substituted with alkyl, alkoxy, —OH, —NO2, —NH2, —COOH, a halogen, and/or —CH3; and isomers, racemates or racemic mixtures thereof, and pharmaceutically acceptable salts or crystalline forms thereof; or a Palmerolide compound of any of formula II or a composition comprising a Palmerolide compound of any of formula II: wherein: =single or double bond R1 is carboxaldehyde, —CHCHNHC(O)-Alkyl, —OC-Alkyl, —OC-aryl, —OC-amino, aryl, amino, -vinylamido, arylamido, alkyl, alkoxy, cycloalkyl, cycloalkoxy, aryloxy, alkylcarbonyl; alkoxycarbonyl, cycloalkylcarbonyl, cycloalkoxycarbonyl, heteroalkyl, heterocycloalkyl, heteroaryl, arylcarbonyl, heteroarycarbonyl, heterocycloalkylcarbonyl, aryloxycarbonyl, heteroaryloxycarbony, heterocycloalkoxycarbonyl, a halogen, or —CHO, any of which can be optionally substituted with H, alkyl alkoxy, —OH, —NO2, —NH2, —COOH, a halogen, or —CH3; R2 is, independently, OH, O-Acyl, carbamate, H, O-alkyl, amino, —OSO3H, alkyl, alkoxy, cycloalkyl, cycloalkoxy, aryloxy, alkylcarbonyl; alkoxycarbonyl, cycloalkylcarbonyl, cycloalkoxycarbonyl, heteroalkyl, heterocycloalkyl, heteroaryl, arylcarbonyl, heteroarycarbonyl, heterocycloalkylcarbonyl, aryloxycarbonyl, heteroaryloxycarbony, heterocycloalkoxycarbonyl, a halogen, and/or oxo; R3 is H, alkyl, alkoxy, cycloalkyl, cycloalkoxy, aryloxy, alkylcarbonyl; alkoxycarbonyl, cycloalkylcarbonyl, cycloalkoxycarbonyl, heteroalkyl, heterocycloalkyl, heteroaryl, arylcarbonyl, heteroarycarbonyl, heterocycloalkylcarbonyl, aryloxycarbonyl, heteroaryloxycarbony, heterocycloalkoxycarbonyl, halogen, any of which can be optionally substituted with alkyl, alkoxy, —OH, —NO2, —NH2, —COOH, a halogen, and/or —CH3; R4 is, independently, H, alkyl, alkoxy, cycloalkyl, cycloalkoxy, aryloxy, alkylcarbonyl; alkoxycarbonyl, cycloalkylcarbonyl, cycloalkoxycarbonyl, heteroalkyl, heterocycloalkyl, heteroaryl, arylcarbonyl, heteroarycarbonyl, heterocycloalkylcarbonyl, aryloxycarbonyl, heteroaryloxycarbony, heterocycloalkoxycarbonyl, halogen, any of which can be optionally substituted with alkyl, alkoxy, —OH, —NO2, —NH2, —COOH, a halogen, and/or —CH3; and isomers, racemates or racemic mixtures thereof, and pharmaceutically acceptable salts or crystalline forms thereof. ### Claim 57 (depends on 56) The kit according to claim 56, wherein said Palmerolide is Palmerolide A, Palmerolidc B, Palmerolide C, Palmerolidc D, Palmerolide E, Palmerolide F, Palmerolide G, Palmerolide H, or Palmerolide K.