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Chemistry and Biochemistry
University of California
230 Physical Sciences Bldg.
Santa Cruz, CA 95064
Phone: (831) 459-4002
Fax: (831) 459-2935
Email
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Phil Crews Professor of Chemistry B.S., University of California, Los Angeles Ph.D., University of California, Santa Barbara Office: 362 PSB Phone: (831) 459-2603 Fax: (831) 459-2935 crews@chemistry.ucsc.edu

Crews Research Group Department of Chemistry University of California 1156 High Street Santa Cruz, CA 95064 Office Hours Class Times & Locations Labs: 343/353/359 PSB, 9-4280 Crews Research Group

RESEARCH INTERESTS: Organic Chemistry, Marine Chemistry, Natural Products

A primary goal of Phillip Crews' marine natural products research is to understand the chemistry of tropical marine sponges. Using bioassay-guided isolation assists us in the discovery of natural products potent against human diseases such as cancer or viruses. Our search for novel active compounds incorporates elements of structure elucidation but there are other dimensions to this research, including questions in the areas of chemical ecology, marine natural products biosynthesis, and the relationship between secondary metabolite chemistry and taxonomy. Added to these interests are emerging projects which examine sponges as a source of new cultured marine microorganisms. We are also interested in examining sponges that are rich with cyanobacterial symbionts.

Whenever possible, we try to use new concise strategies to elucidate structures, including gradient 2D NMR techniques such as gs-HMBC, gs-HMQC, gs-COSY, gs-TOCSY, gs-NOESY, and ¹H-¹⁵N gs HMQC. Utilization of new NMR hardware, 3mm probes and advanced NMR microtubes, addresses problems of limited amounts of sample. Another goal is to engage in follow-up studies that employ molecular mechanics data combined with these state-of-the-art NMR techniques.

An additional subject of interest is to explore marine fungi as a source of secondary metabolites. The goal is to isolate novel bioactive substances from fungi cultured from marine sponges in order to discover new structural classes of natural products. We are developing strategies that will maximize the diversity and secondary metabolite production of cultured marine fungi.

Shown below are two examples of novel compounds that were discovered in our laboratory from sponges collected from Papua New Guinea. Each exhibits interesting bioactivity.

SELECTED PUBLICATIONS

Robinson, S. J.; Tenney, K.; Yee, D. F.; Martinez, L.; Media, Joseph E.; Valeriote, F.
A.; van Soest, Rob W. M.; Crews, P. Probing the Bioactive Constituents from Chemotypes of the Sponge Psammocinia aff. Bulbosa. J. Nat. Prod. 2007, 70, 1002-1009.

Hu, X.; Dang, Y.; Tenney, K.; Crews, P.; Cole, P.; Liu, J. O. Regulation of c-Scr Non-receptor Tyrosine
Kinase Activity by Bengamide A Through Inhibition of Methionine Aminopeptidases. Chem. Biol. 2007,14, 764-774.

Li, H.; Amagata, T ; Tenney, K.; Crews, P. Additional Scalarane Sesterterpenes from the Sponge
Phyllospongia papyracea. J. Nat. Prod. 2007, 70, 802-807.

Boot, C. M.; Amagata, T.; Tenney, K.; Compton, J. E.; Pietraszkiewicz, H.; Valeriote, F. A.; Crews, P.
Four Classes of Structurally Unusual Peptides from two Marine-Derived Fungi: Structures and
Bioactivities. Tet. 2007, 63, 9903-9914.

Johnson, T.; Tenney, K.; Cichewicz, R.; Morinaka, B.; White, K.; Amagata, T.; Subramanian, B.;
Media, J.; Mooberry, S.; Valeriote, F. A.; Crews, P. Sponge-Derived Fijianolide Polyketide Class:
Further Evaluation of Their Structural and Cytotoxicty Properties. J. Med. Chem.
2007, 50, 3795-3803.

Rubio, B. K.; van Soest, Rob W. M.; Crews, P. Extending the Record of Meroditerpenes from Cacospongia Marine Sponges. J. Nat. Prod. 2007, 70, 628-631.

Pina, I.; White, K.; Cabrera, G.; Rivero, E.; Crews, P. Bromopyrrole Carboxamide Biosynthetic
Products from the Caribbean Sponge Agelas dispar. J. Nat. Prod. 2007, 70, 613-617.

Ralifo, P.; Sanchez, L.; Gassner, N.; Tenney, K.; Lokey, S.; Holman, T.; Valeriote, F. A.; Crews, P.
Pyrroloacridine Alkaloids from Plakortis quasiamphiaster- Structures and Bioactivity. J. Nat. Prod.
2007, 70, 95-99.

Gassner, N.; Tamble, C.; Bock, J.; Cotton, N.; White, K.; Tenney, K.; Onge, R.; Proctor, M.;
Giaever, G.; Davis, R.; Crews, P.; Holman, T.; Lokey, S. Accelerating the Discovery of Biologically
Active Small Molecules Using a High-Throughput Yeast Halo Assay. J. Nat. Prod. 2007, 70, 383-390.

Wegerski, C.; Hammond, J.; Tenney, K.; Matainaho, T.; Crews, P. A Serendipitous Discovery of
Isomotuporin-Containing Sponge Populations of Theonella swinhoei. J.Nat. Prod. 2007, 70, 89-94.

Ralifo, P.; Tenney, K.; Valeriote F. A.; Crews, P. A Distinctive Structural Twist in the Aminoimidazole
Alkaloids from a Calcareous Marine Sponge-Isolation and Characterization of Leucosolenamines A
and B. J. Nat. Prod. 2007, 70, 33-38.

Gautschi J. T.; Tenney, K.; Compton, J.; Crews, P. Chemical Investigations of a Deep Water Marine
Derived Fungus: Simple Amino Acid Derivatives from an Arthrinium sp. Nat. Prod. Comm. 2007, 2,
541-546.

Amagata, T.; Morinaka, B.; Amagata, A.; Tenney, K.; Valeriote, F. A.; Lobkovsky, E.; Clardy, J.;
Crews, P. A Chemical Study of Cyclic Depsipeptides Produced by a Sponge-Derived Fungus. J. Nat.
Prod. 2006, 69, 1560-1565.

Wegerski, C.; Sonnenschein, R. N.; Valeriote F. A.; Matainaho F. A.; Crews, P. Stereochemical
Challenges In Characterizing Nitrogenous Spiro-Axane Sesquiterpenes from the Indo-Pacific sponges
Amorphinopsis and Axinyssa. Tetrahedron, 2006, 62, 10393-10399.

Sonnenschein, R. N.; Johnson, T. A.; Tenney, K.; Valeriote F. A.; Crews, P. A Reassignment of (-)
and the Isolation of the Related Diol. J. Nat. Prod. 2006, 69, 145-147.

Boot, C. M.; Tenney, K.; Valeriote, F. A.; Crews, P. Highly N-Methylated Linear Peptides Produced
by an Atypical Sponge-Derived Acremonium sp. J. Nat. Prod. 2006, 69, 83-92.

Subramanian, B.; Nakeff, A.; Tenney, K.; Crews, P.; Gunatilaka, L.; Valeriote, F. A. A New Paradigm
for the Development of Anticancer Agents from Natural Products. J. Exp. Therap. Onc. 2006, 5, 195-
204.

Christian, O. E.; Compton, J.; Christian; K. R.; Mooberry, S. L.; Valeriote, F. A.; Crews, P. Using
Jasplankinolide to Turn on Pathways that Enable the Isolation of New Chaetoglobosins from
Phomospis asparagi. J. Nat. Prod. 2005, 68, 1592-1597.

Segraves, N. L.; Crews, P. Investigation of Brominated Tryptophan Alkaloids from Two Thorectidae
Sponges: Thorectandra and Smenospongia. J. Nat. Prod. 2005, 68, 1484-1488.

Cichewicz, R. H.; Clifford, L. J.; Lassen, P. R.; Cao, X.; Freedman, T. B.; Nafie, L. A.; Deschamps,
J. D.; Kenyon, V. A.; Flanary, J. R.; Holman, T. R.; Crews, P. Stereochemical Determination and
Bioactivity Assessment of (S)-(+)-curcuphenol Dimers Isolated from the Marine Sponge Didiscus
aceratus and Synthesized through Laccase Biocatalysis. Bioorg. Med. Chem. 2005, 13, 5600-5612.

Flatt, P. M.; Gautschi, J. T.; Thacker, R. W.; Musafija-Girt, M.; Crews, P.; Gerwick, W. H.
Identification of the Cellular Site of Polychlorinated Peptide Biosynthesis in the Marine Sponge
Dysidea (Lamellodysidea) herbacea and Symbiotic cyanobacterium Oscillatoria spongeliae by CARD
FISH Analysis. Mar. Bio. 2005, 147, 761-774.

Segraves, N. L.; Crews, P. A Madagascar Sponge Batzella sp. as a Source of Alkylated Iminosugars. J. Nat. Prod. 2005, 68, 118-121.

Crews, P.; Gerwick, W. H.; Schmitz, F. J.; France, D.; Blair, K. W.; Wright, A. M.; Hallock, Y. Molecular
Approaches to Discover Marine Natural Product Anticancer Leads - An Update from a Drug
Discovery Group Collaboration. Pharm. Biol. 2004, 41, 39-52.

Ralifo, P.; Crews, P. A New Structural Theme in the Imidazole Containing Alkaloids from a Calcareous Leucetta Sponge. J. Org. Chem. 2004, 69, 9025-9029.

Cichewicz, R. H.; Kenyon, V. A.; Whitman, S.; Morales, N. M.; Arguello, J. F.; Holman, T. R.; Crews, P. Redox Inactivation of  Human 15-Lipoxygenase by   Marine- Derived Meroditerpenes and Synthetic Chromanes: Archetypes for a Unique Class of Selective and Recyclable Inhibitors. J. Am. Chem. Soc. 2004, 126, 14910-14920.

Wegerski, C. J.; France, D.; Cornell-Kennon, S.; Crews, P. Using a Kinase Screen to Investigate the Constituents of the Sponge Stelleta clavosa Obtained from Diverse Habitats. Bioorg. Med. Chem.2004, 12, 5631-5637

Segraves, E. N.; Shah, R. R.; Segraves, N. L.; Johnson, T. A.; Whitman, S.; Sui, J. K.; Kenyon, V. A.; Cichewicz, R. H.; Crews, P.; Holman, T. R. Probing the Activity Differences of Simple and Complex Brominated Aryl Compounds against 15-Soybean, 15-Human and 12-Human Lipoxygenases. J. Med. Chem.2004, 47, 4060-4065.

Gautschi, J. T.; Whitman, S.; Holman, T. R.; Crews, P.AN Analysis of Phakellin and Oroidin Structures Stimulated by Further Study of an Agelas Sponge. J. Nat. Prod.2004, 67, 1256-1261.

Vilozny, B.; Amagata, T.; Mooberry, S. L.; Crews, P. A New Dimension to the Biosynthetic Products Isolated from the Sponge Negombata magnifica. J. Nat. Prod. J. Nat. Prod. 2004, 67, 1055-1057.

Cichewicz, R. H.; Valeriote, F. A.; Crews, P. Psymberin, A Potent Sponge-Derived Cytotoxin from Psammocinia Distantly Related to the Pederin Family. Org. Lett.2004, 6, 1951-1954.

Segraves, N. L.; Robinson, S. J.; Garcia, D.; Said, S. A.; Fu, X.; Schmitz, F. J.; Petraszkiewicz, H.; Valeriote, F. A.; Crews, P. Comparison of Fascaplysin and Related Alkaloids – A Study of Structures, Cytotoxicities, and Sources. J. Nat. Prod.2004, 67, 783-792.

Gautschi, J. T.; Amagata, T.; Amagata, A.; Valeriote, F. A.; Mooberry, S. L.; Crews, P. Expanding the Strategies in Natural Product Studies of Marine-Derived Fungi: A Chemical Investigation of Penicillium Obtained from Deep Water Sediment. J. Nat. Prod.2004, 67, 362-367.

Sonnenschein, R. N.; Farias, J. J.; Tenney, K.; Mooberry, S. L.; Lobkovsky, E.; Clardy, J.; Crews, P. A Further Study of the Cytotoxic Constituents of a Milnamide Producing Sponge. Org. Lett.2004, 6, 779-782.

Lepourcelet, M.; Chen, Y.-N. P.; France, D. S.; Wang, H.; Crews, P.; Petersen, F.; Bruseo, C.; Wood, A. W.; Shivdasani, R. A. Small-Molecule Antagonists of the Oncogenic Tcf/b-Catenin Protein Complex. Cancer Cell2004, 5, 91-102.

Crews, P.; Gerwick, W. H.; Schmitz, F. J.; France, D.; Bair, K. W.; Wright, A. E.; Hallock, Y. Molecular Approaches to Discover Marine Natural Product Anticancer Leads – An Update from a Drug Discovery Group Collaboration. Pharm. Biol.2003, 41, 39-52.

Amagata, T.; Amagata, A.; Tenney, K.; Valeriote, F. A.; Lobkovsky, E.; Clardy, J.; Crews, P. Unusual C25 Steroids Produced by a Sponge-Derived Penicillium citrinum. Org. Lett.2003, 5, 4393-4396.

Amagata, T.; Rath, C.; Rigot, J. F.; Tarlov, N.; Tenney, K.; Valeriote, F. A.; Crews, P. Structures and Cytotoxic Properties of Trichoverroids and their Macrolide Analogues Produced by Saltwater Culture of Myrothecium verrucaria. J. Med. Chem.2003, 46, 4342-4350.

Edrada, R. A.; Stessman, C. C.; Crews, P. Uniquely Modified Imidazole Alkaloids from a Calcareous Leucetta Sponge. J. Nat. Prod.2003, 66, 939-942.

Wenzel, P. J.; Crews, P. Probing Biotransformation Relationships Among Pyridoacridines by Focusing on Oxygenated Analogs. J. Nat. Prod.2003, 66, 873-875.

Piña, I. C.; Gautschi, J. T.; Wang, G.-Y.-S.; Sanders, M. L.; Schmitz, F. J.; France, D.; Cornell-Kennon, S.; Sambucetti, L. C.; Remiszewski, S. W.; Bair, K. W.; Crews, P. Psammaplins from the Sponge Psuedoceratina purpurea: Inhibition of Both Histone Deacetylase and DNA Methyltransferase. J. Org. Chem.2003, 68, 3866-3873.

Segraves, N. L.; Lopez, S.; Johnson, T. A.; Said, S. A.; Fu, X.; Schmitz, F. J.; Pietraszkiewicz, H.; Valeriote, F. A.; Crews, P. Structures and Cytotoxicities of Fascaplysin and Related Alkaloids from Two Marine Phyla - Fascaplysinopsis Sponges and Didemnum Tunicates. Tetrahedron Lett.2003, 44, 3471-3475.

Amagata, T.; Whitman, S.; Johnson, T. A.; Stessman, C. C.; Loo, C.; Lobkovsky, E.; Clardy, J.; Crews, P.; Holman, T. R. Explored Sponge-Derived Terpenoids for their Potency and Selectivity Against 12-Human, 15-Human, and 15-Soybean Lipoxygenases. J. Nat. Prod. 2003, 66, 230-235.

Crews, P.; Clark, D. P.; Tenney, K. Variation in the Alkaloids Among Indo-Pacific Leucetta Sponges. J. Nat. Prod.2003, 66, 177-182.

Piña, I. C.; Sanders, M. L.; Crews, P. Puupehenone Congeners from an Indo- Pacific Hyrtios Sponge. J. Nat. Prod.2003, 66, 2-6.

Thale, Z.; Johnson, T.; Tenney, K.; Wenzel, P. J.; Lobkovsky, E.; Clardy, J.; Media, J.; Pietraskiewicz, H.; Valeriote, F. A.; Crews, P. Structures and Cytotoxic Properties of Sponge-Derived Bisannulated Acridines. J. Org. Chem.2002, 67, 9384-9391.

Stessman, C. C.; Ebel, R.; Corvino, A. J.; Crews, P. Employing Dereplication and Gradient 1D-NMR Methods to Rapidly Characterize Sponge-Derived Sesterterpenes. J. Nat. Prod.2002, 65, 1183-1186.

Braet, F.; Spector, I.; Shochet, N.; Crews, P.; Higa, T.; Menu, E.; De Zanger, R.; Wisse, E. The New Anti-Actin Agent Dihydrohalichondramide Reveals Fenestrae-Forming Centers in Hepatic Endothelial Cells. BMC Cell Biol.2002, 3:7.

Carroll, J.; Jonsson, E. N.; Ebel, R.; Hartman, M. S.; Holman, T. R.; Crews, P. Probing Sponge-Derived Terpenoids for Human 15-Lipoxygenase Inhibitors. J. Org. Chem.2001, 66, 6847-6851.

Kinder, F. R., Jr.; Versace, R. W.; Bair, K. W.; Bontempo, J. M.; Cesarz, D.; Chen, S.; Crews, P.; Czuchta, A. M.; Jagoe, C. T.; Mou, Y.; Nemzek, R.; Phillips, P. E.; Tran, L. D.; Wang, R.; Weltchek, S.; Zabludoff, S. Synthesis and Antitumor Activity of Ester-Modified Analogues of Bengaminde B. J. Med. Chem.2001, 44, 3692-3699.

Thale, Z.; Kinder, F. R.; Bair, K. W.; Bontempo, J.; Czuchta, A. M.; Versace, R. W.; Phillips, P. E.; Sanders, M. L.; Wattanasin, S.; Crews, P. Bengamides Revisited: New Structures and Antitumor Studies. J. Org. Chem.2001, 66, 1733-1741.

Odaka, C.; Sanders, M. L.; Crews, P. Jasplakinolide Induces Apoptosis in Various Transformed Cell Lines by a Caspase-3-Like Protease-Dependent Pathway. Clin. Diagn. Lab. Immun.2000, 7, 947-951.

Crews, P.; Harrison, B. New Triterpene-Ketides (Merotriterpenes), Haliclotriol A and B, from an Indo-Pacific Haliclona Sponge. Tetrahedron2000, 56, 9039-9046.

Wood, W. F.; Hanke, F. J.; Kubo, I.; Carroll, J. A.; Crews, P. Buzonamine, a New Alkaloid from the Defensive Secretion of the Millipede, Buzonium crassipes. Biochem. Syst. Ecol.2000, 28, 305-312.

Varoglu, M; Crews, P. Biosynthetically Diverse Compounds from a Saltwater Culture of Sponge-Derived Aspergillus niger. J. Nat. Prod.2000, 63, 41-43.