# US 5,352,804 A · Isolation and structure of Halistatin 2

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- Number: US 5,352,804 A
- Document ID: US5352804A
- Status: Granted
- Kind: A
- Application number: 08/004,852
- Filed: 1993-01-19
- Granted: 1994-10-04
- Earliest claimed: 1993-01-19
- Assignees: Arizona Board of Regents, a body corporate acting on behalf of Arizona State University
- Inventors: George R. Pettit; Feng Gao
- Web page: https://patentgrep.com/patent/US5352804A

## CPC

- C07D 493/22: in which the condensed system contains four or more hetero rings
- A61P 35/00: Antineoplastic agents
- A61P 35/02: specific for leukemia
- C07H 9/02: the hetero ring containing only oxygen as ring hetero atoms
- C12P 17/181: {Heterocyclic compounds containing oxygen atoms as the only ring heteroatoms in the condensed system, e.g. Salinomycin, Septamycin}
- C12P 19/445: {The saccharide radical is condensed with a heterocyclic radical, e.g. everninomycin, papulacandin}
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07H: SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS (derivatives of aldonic or saccharic acids C07C, C07D; aldonic acids, saccharic acids C07C59/105, C07C59/285; cyanohydrins C07C255/16; glycals C07D; compounds of unknown constitution C07G; polysaccharides, derivatives thereof C08B; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification C12N15/00; sugar industry C13)
- C12P: FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE {(brewing of beer C12C; producing vinegar C12J; producing specific peptides or proteins C07K; producing enzymes C12N9/00; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification C12N15/00; measuring or testing processes involving enzymes or microorganisms C12Q; measuring or testing processes involving nucleic acid amplification reactions C12Q1/6844; fermentation processes to form a food composition, A21 or A23; compounds in general, see the relevant compound class, e.g. C01, C07)}

## Abstract

An intensive long-term investigation of marine organisms as sources of new anticancer drugs has led to the isolation and structural elucidation (primarily by high field NMR and mass spectrometry) of halistatin 2, a new polyether macrolide of the halipyran-type, from the Western Indian Ocean sponge Axinella cf. carteri (Dendy). Halistatin 2 (1.4.times.10.sup.-6 % yield) caused the accumulation of cells arrested in mitosis, inhibited tubulin polymerization, and inhibited the binding of radiolabeled vinblastine and GTP to tubulino. Further, Halistatin 2 displayed significant activity against selected human tumor cell lines.

## Claims

### Claim 1

A composition of matter denominated halistatin 2 and having the following structural formula: ##STR6##

### Claim 2

A composition of matter denominated halistatin 2 and having the following NMR assignments:
______________________________________ XHCorr. .sup.13 C(100 MHz) (400 MHz) HMBC(500 MHz) ______________________________________ 1 172.86p H-2,H-30 2 41.19p 2.55 dd(10,18); 2.46 brd(18) 3 75.00n 3.91 H-2 4 31.61p 6 71.20n 4.45 H-7,H-8 7 78.84n 3.05 dd(1.8,9.7) H-8 8 75.16n 4.24 H-7,H-9 9 79.77n 3.74 brd(4.4) H-8,H-11,H-12 10 103.75p H-8,H-9,H-11,H-12 11 87.64n 4.25 H-9,H-12,H-13 12 82.29n 4.73 t(4.6) H-9,H-11,H-13 13 49.00p 2.13;1.96 dd(5,13) 14 110.83p H-8,H-11,H-12,H-13 16 29.37p 2.17;1.40 H-18 17 77.18n 4.07 H-18 18 39.75p 2.80 brm;2.32 H-19a 19 153.16p H-18,H-17,H-19a 19a 105.65p 5.05 brs;5.00 brs H-18 20 76.07n 4.45 H-19a 23 75.45n 3.69 brt(10) 24 44.96p 1.72;1.02 H-25a 25 37.22n 2.32 H-25a,H-24,H-26a 25a 18.41n 1.08 d(6.4) H-24 26 153.32p H-27,H-25,H-25a,H-24, H-26a 26a 104.79p 4.86 brs;4.80 brs H-27,H-28 27 75.07n 3.60 H-29,H-26a 28 37.90p 2.25;1.80 H-29,H-30 29 73.78n 4.23 H-27,H-25 30 77.56n 4.62 dd(4.7,7.6) H-29,H-31a 31 37.50n 2.05 H-29,H-31a 31a 15.76n 1.04 d(7.1) H-30,H-31,H-32 32 78.20n 3.20 dd(4.9,6.7) H-30,H-31a,H-33 33 65.95n 3.88 H-29,H-32 34 30.85p 2.04;1.80 H-33,H-36 35 76.34n 4.10 H-36 36 78.01n 4.10 H-35 37 45.51p 2.39;2.00 38 114.78p H-36,H-37,H-39,H-40 39 44.84p 2.30;2.30 40 72.31n 3.94 brs H-39,H-41 41 81.06n 3.65 brt(2.8) H-42a,H-39 42 27.15n 2.36 H-42a,H-43 42a 18.18n 0.94 d(7.0) H-43 43 38.09p 1.43;1.33 H-42a,H-41 44 98.14p H-43 45 38.17p H-46a,H-47 46 30.14n 2.18 H-46a,H-47 46a 17.65n 0.93 d(6.8) H-47 47 74.57n 3.11 brd(2.2) H-46a 48 65.31n 3.57 H-47 49 32.03p 2.10;1.92 H-48 50 75.81n 3.86 H-48,H-51 51 78.44n 4.01 brs H-47,H-50 52 37.29p 2.02; 53 79.87n 4.24 H-55,H-51 54 75.16n 3.49 brdd(5.5,10) H-55 55 65.18p 3.56 brs;3.56 brs ______________________________________