Abstract: The purification and structure elucidation of several products of the metabolism of Et 743 by human cytochrome CYP3A4 have been accomplished. These compounds are abbreviated herein as “ETM” followed by a numeric value, which represents the approximate molecular weight. Three compounds have been identified to date, namely ETM 305, ETM 775 and ETM 204.

Abstract: Disclosed are semi-synthetic methods for the preparation of Didemnin analogs. The compounds of this type are illustrated in Formula (I).

Abstract: The present invention is based upon the immunomodulatory activity of synthetic and semi-synthetic didemnin compounds. It has surprisingly been discovered that certain didemnin compounds possess unexpectedly high immunomodulation activity, and thus will be useful for modulating or regulating immunological functions in warm blooded animals. From the data provided herein it is believed that the physician will be able to determine the appropriate dosage of the immunosuppressant didemnins of the present invention. The actual dosage to be administered depends, inter alia, on the animal species to be treated, the subject animal's size, and the capacity of the subject to utilize the particular didemnin compound administered. Accordingly, the actual amounts of any didemnin compound required to be administered depend on the judgment of the practitioner.

Abstract: Dehydrodidemnin B with useful biological activity has formula (1). It can be isolated from natural sources or synthesized, and it forms active derivatives.

Abstract: The present invention is directed to several newly prepared semi-synthetic ecteinascidin (Et) species, designated herein as Et 757, Boc-Et 729, Iso-Et 743, Et 875, and Et 1560. The physical properties of these compounds, their preparation and bioactivities are also reported.

Abstract: The present invention is directed to the isolation and bioactive characterization of compounds isolated from the clam Spisula polynyma. These compounds include three sphingoid-type bases, spisulosines 285, 299 and 313 (1-3), each of which shows unique cytotoxicity against L1210 murine lymphocytic leukemia cells. In addition, sphingosine (also referred to as 4-sphingenine or octadeca-4-shpingenine, 4) and two related compounds, nonadeca-4-sphingenine (a one carbon longer homolog, 5) and sphinga-4,10-diene (a dehydrosphingosine deravitive, 6) were also obtained, These compounds also contribute to the cytotoxicity of the Spisula polynyma extracts, but did not cause the morphology changes observed with compounds 1-3.

Abstract: The didemnin class of biologically active cyclodepsipeptides, isolated from the marine tunicate Trididemnun solidum, has shown considerable antitumor, antiviral, and immunosuppressive activities. Didemnin B (DB) and most other natural didemnins contain a common macrocycle and differ only in the composition of the side chain. In the present invention, structural modifications were introduced in the side chain to afford several didemnin analogues for structure-activity relationship studies. The latter have shown that the linear side chain portion of the didemnin core structure can be altered and, in some cases, provide significant gains in bioactivities. Of the compounds synthesized the new [Ala.sup.9 ] didemnin B is the most active against the L1210 (murine leukemia) cell line, at the 0.04 ng/mL level.

Abstract: The present invention is directed to the isolation and characterization of six new crambescidin compounds, the structures of which are shown below: ##STR1## .

Abstract: Five new nucleophile substituted ecteinascidin (Et) compounds have been isolated from extracts of Ecteinascidia turbinata. These compounds have been purified by chromatographic techniques and their structures and bioactivities have been determined. The five nucleophile substituted Et compounds have been designated herein as Et 802 (1), Et 788 (2), Et 760 (3), Et 858 (4) and Et 815 (5). Also obtained were three new N-oxide ecteinascidin compounds, which have been designated herein as Et 717 (6), Et 775 (7) and Et 789 (8). Some of these newly discovered Et compounds show exceedingly potent cytotoxicity against L1210.

Abstract: The present invention is directed to several novel compounds isolated from the sponge Crambe crambe, and designated herein as Crambescidin 816 (Compound 1), Crambescidin 830 (Compound 2), Crambescidin 844 (Compound 3), and Crambescidin 800 (Compound 4), as well as several derivatives thereof. The 816, 830, 844 and 800 compounds are four preferred species of complex pentacyclic guanidines linked by a linear .omega.-hydroxy fatty acid to a hydroxyspermidine, that have been obtained by a bioassay-guided isolation procedure, involving solvent partition and chromatography on Sephadex LH-20, cyano, and C-18 columns, from extracts of the red, encrusting sponge Crambe crambe (Order Poecilosclerida, Family Esperiopsidae).

Abstract: Dehydrodidemnin B with useful biological activity has formula (1). It can be isolated from natural sources or synthesized, and it forms active derivatives.

Abstract: The present invention is directed to several novel compounds isolated from the sponge Crambe crambe, and designated herein as Crambescidin 816 (Compound 1), Crambescidin 830 (Compound 2), Crambescidin 844 (Compound 3), and Crambescidin 800 (Compound 4), as well as several derivatives thereof. The 816, 830, 844 and 800 compounds are four preferred species of complex pentacyclic guanidines linked by a linear .omega.-hydroxy fatty acid to a hydroxyspermidine, that have been obtained by a bioassay-guided isolation procedure, involving solvent partition and chromatography on Sephadex LH-20, cyano, and C-18 columns, from extracts of the red, encrusting sponge Crambe crambe (Order Poecilosclerida, Family Esperiopsidae).

Abstract: The present invention is based upon the discovery that a MeOH extract of Anabaena affinis strain VS-1 showed strong cytotoxicity to L1210 murine leukemia cells, and from that extract was isolated the compounds having the following structures, Compounds 1 and 2. These two compounds are believed to be responsible for the cytotoxicity of the marine organism. This is the first report of the isolation and characterization of pyrrolo?3,2-d!pyrimidine derivatives as biosynthetic products.

Abstract: Ecteinascidins (Et's), isolated from the Caribbean tunicate Ecteinascidia turbinata, protect mice in vivo against P388 lymphoma, B16 melanoma, M5076 ovarian sarcoma, Lewis lung carcinoma, and the LX-1 human lung and MX-1 human mammary carcinoma zenografts.

Abstract: The present invention is based upon the discovery that a MeOH extract of Anabaena affinis strain VS-1 showed strong cytotoxicity to L1210 murine leukemia cells, and from that extract was isolated the compounds having the following structures, Compounds 1 and 2. These two compounds are believed to be responsible for the cytotoxicity of the marine organism. This is the first report of the isolation and characterization of pyrrolo[3,2-d] pyrimidine derivatives as biosynthetic products.

Abstract: The present invention is based upon the discovery that the methanol extract of the bryozoan Myriapora truncata showed potent cytotoxicity against L1210 murine leukemia cells (99% inhibition at 50 .mu.g/mL). Fractionation and purification of active components from this extract, guided by a cytotoxicity assay, resulted in the isolation of a novel, highly cytotoxic polyketide-derived metabolite MT-332 (Compound 3) and its equilibrium isomer (Compound 4), along with two less active compounds, MT-381 (Compound 1) and MT-381-B (Compound 2). The equilibrium mixture of Compounds 3 and 4 showed 88% inhibition at 0.2 .mu.g/mL against L1210 cells.

Abstract: Ecteinascidins (Et's), isolated from the Caribbean tunicate Ecteinascidia turbinata, protect mice in vivo against P388 lymphoma, B16 melanoma, M5076 ovarian sarcoma, Lewis lung carcinoma, and the LX-1 human lung and MX-1 human mammary carcinoma zenografts.

Abstract: This invention is directed to didemnin derivatives, including N-acyl congeners of didemnin A (DA); several DDB-type analogues of DA in which either pyruvic acid has been replaced (with phenylpyruvic acid or alphaketobutyric acid) or proline at position 8 has been replaced [with L-azetidine-2-carboxylic acid (AZT), L-pipecolic acid (Pip), 1-amino-1-carboxylic cyclopentane (acc.sup.5), D-Pro or sarcosine (sar); and other cyclic depsipeptides related to the didemnins, which were isolated from a relatively polar extract of the tunicate T. solidum; namely the didemnins--X [(R)-3-hydroxy-decanoyl-(Gln).sub.3 -Lac-Pro didemnin A]; Y [(R)-3-hydroxy-decanoyl-(Gln).sub.4 -Lac-Pro didemnin A]; M (pGlu-Gln-Lac-Pro-didemnin A); N ([Tyr.sup.5 ] didemnin B); nordidemnin N ([Tyr.sup.5 ] nordidemnin B); and epididemnin A ([2S,4R-Hip.sup.2 ] didemnin A).

Abstract: Novel antibiotics didemnins A, B and C (didemnins), and nordidemnins A, B and C (nordidemnins) which can be obtained from a marine organism. These antibiotics are active against a variety of DNA and RNA viruses; thus, they can be used in various environments to control or eradicate these viruses. Further, these antibiotics can be used to treat animals and humans hosting a neoplastic disease.

Abstract: The present invention relates to novel compositions of matter extracted from the well-known and readily available tropical marine invertebrate, Ecteinascidia turbinata, and designated herein as ecteinascidins 729, 743, 745, 759A, 759B and 770. These compounds are useful as antibacterial and/or antitumor agents in mammals.