The enduring legacy of Koji Nakanishi's research on bioorganic chemistry and natural products. Part 1: Isolation, structure determination and mode of action.

In this brief review on Koji Nakanishi's remarkable career in natural products chemistry, we have highlighted a number of his accomplishments that illustrate the broad diversity of his interests. These include the isolation, structure determination, and biological mechanism of action of many natural products including the triterpenoid pristimerin; the diterpenoid ginkgolides; insect and crustacean molting hormones; phytoalexins; the toxic red tide principle brevetoxin; the vanadium tunicate pigments; philanthotoxin from killer wasps; antisickling agents; mitomycin DNA adducts; insect antifeedants; a mitotic hormone, the small molecule fish attractants from the sea anemone; new isolation and purification technologies; molecular chemistry of vision; age-related macular degeneration; and the development of the exciton circular dichroism (CD) chirality method for microscale determination of absolute configuration of natural products and chirality of other chiral molecules and supramolecular assembly.

[1]  Jian-ye Zhang,et al.  Anti-Cancer Effects of Pristimerin and the Mechanisms: A Critical Review , 2019, Front. Pharmacol..

[2]  K. Nakanishi,et al.  Identification of ginkgolide targets in brain by photoaffinity labeling , 2017, Chemical biology & drug design.

[3]  John L. Murphy,et al.  Synthesis of antioxidants for prevention of age-related macular degeneration. , 2013, Journal of natural products.

[4]  W. Robinson,et al.  Structure, biosynthesis and possible function of tunichromes and related compounds. , 2012, Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology.

[5]  R. Morimoto,et al.  Remarkable stereospecific conjugate additions to the Hsp90 inhibitor celastrol. , 2011, Journal of the American Chemical Society.

[6]  K. Nakanishi,et al.  Synthesis of Antioxidant Flavonoid Derivatives. , 2011 .

[7]  K. Nakanishi,et al.  Calicheamicin γ1(I) and phenyl tert-butyl nitrone (PBN): observation of a kinetic isotope effect by an ESR study. , 2010, Chemical communications.

[8]  K. Nakanishi,et al.  Synthesis of antioxidant flavonoid derivatives , 2010 .

[9]  K. Nakanishi,et al.  Inherent chirality dominates the visible/near-ultraviolet CD spectrum of rhodopsin. , 2008, Journal of the American Chemical Society.

[10]  S. Jockusch,et al.  Superoxidation of bisretinoids. , 2005, Angewandte Chemie.

[11]  E. Giorgio,et al.  Theoretical simulation of the electronic circular dichroism spectrum of calicheamicin. , 2005, Bioorganic & medicinal chemistry.

[12]  Koji Nakanishi,et al.  Terpene trilactones from Gingko biloba: from ancient times to the 21st century. , 2005, Bioorganic & medicinal chemistry.

[13]  Katsunori Tanaka,et al.  Three challenges toward the assignment of absolute configuration of gymnocin-B. , 2005, Journal of the American Chemical Society.

[14]  K. Nakanishi,et al.  Anthocyanins Protect Against A2E Photooxidation and Membrane Permeabilization in Retinal Pigment Epithelial Cells ¶ , 2005 .

[15]  K. Nakanishi,et al.  Chemistry and biology of terpene trilactones from Ginkgo biloba. , 2004, Angewandte Chemie.

[16]  K. Nakanishi,et al.  Determination of the absolute configuration of Anisotome irregular diterpenes: application of CD and NMR methods. , 2004, Chirality.

[17]  K. Nakanishi,et al.  Absolute configurational determination of an all-trans-retinal dimer isolated from photoreceptor outer segments. , 2004, Chirality.

[18]  A. Kriegstein,et al.  Terpene Trilactones from Ginkgo biloba Are Antagonists of Cortical Glycine and GABAA Receptors* , 2003, Journal of Biological Chemistry.

[19]  N. Berova,et al.  Theoretical analysis of the porphyrin-porphyrin exciton interaction in circular dichroism spectra of dimeric tetraarylporphyrins. , 2003, Journal of the American Chemical Society.

[20]  Koji Nakanishi,et al.  A2-rhodopsin: a new fluorophore isolated from photoreceptor outer segments. , 2003, Organic & biomolecular chemistry.

[21]  K. Nakanishi,et al.  Preparation of 7-substituted ginkgolide derivatives: potent platelet activating factor (PAF) receptor antagonists. , 2003, Journal of medicinal chemistry.

[22]  K. Nakanishi,et al.  Configurational assignment of α-chiral carboxylic acids by complexation to dimeric Zn–porphyrin: host–guest structure, chiral recognition and circular dichroism , 2002 .

[23]  K. Nakanishi,et al.  Solution and biologically relevant conformations of enantiomeric 11-cis-locked cyclopropyl retinals. , 2002, Journal of the American Chemical Society.

[24]  S. Jockusch,et al.  Formation of a Nonaoxirane from A2E, a Lipofuscin Fluorophore related to Macular Degeneration, and Evidence of Singlet Oxygen Involvement , 2002 .

[25]  S. Jockusch,et al.  Formation of a nonaoxirane from A2E, a lipofuscin fluorophore related to macular degeneration, and evidence of singlet oxygen involvement. , 2002, Angewandte Chemie.

[26]  Tao Wang,et al.  On the bioactive conformation of the rhodopsin chromophore: absolute sense of twist around the 6-s-cis bond. , 2001, Chemistry.

[27]  X. Huang,et al.  Chiral recognition by CD-sensitive dimeric zinc porphyrin host. 1. Chiroptical protocol for absolute configurational assignments of monoalcohols and primary monoamines. , 2001, Journal of the American Chemical Society.

[28]  N. Nesnas,et al.  Chiral recognition by CD-sensitive dimeric zinc porphyrin host. 2. Structural studies of host-guest complexes with chiral alcohol and monoamine conjugates. , 2001, Journal of the American Chemical Society.

[29]  K. Nakanishi,et al.  Movement of retinal along the visual transduction path. , 2000, Science.

[30]  X. Huang,et al.  Porphyrins and metalloporphyrins: versatile circular dichroic reporter groups for structural studies. , 2000, Chirality.

[31]  K. Nakanishi,et al.  Absolute stereochemistry of the strevertenes. , 2000, Chirality.

[32]  K. Nakanishi,et al.  Nanogram scale absolute configurational assignment of ceramides by circular dichroism , 1999 .

[33]  K. Nakanishi,et al.  Efficient Synthesis of 11-cis-Retinoids , 1999 .

[34]  M. Schwarz,et al.  2.14 – Ginkgolide Biosynthesis , 1999 .

[35]  K. Nakanishi,et al.  Isolation and one-step preparation of A2E and iso-A2E, fluorophores from human retinal pigment epithelium. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[36]  K. Nakanishi,et al.  Mechanism of Transient Dark Activity of 13-Desmethylretinal/Rod Opsin Complex , 1998 .

[37]  K. Nakanishi,et al.  Zinc Porphyrin Tweezer in Host−Guest Complexation: Determination of Absolute Configurations of Diamines, Amino Acids, and Amino Alcohols by Circular Dichroism , 1998 .

[38]  K. Nakanishi,et al.  A two-step chemical/chiroptical method for determining absolute configurations of α-hydroxy acids , 1998 .

[39]  K. Nakanishi,et al.  Total Synthesis of the Ocular Age Pigment A2-E: A Convergent Pathway , 1997 .

[40]  K. Nakanishi,et al.  Reactions between tunichrome Mm-1, a tunicate blood pigment, and vanadium ions in acidic and neutral media. , 1996, Biochemistry.

[41]  K. Nakanishi,et al.  Structural Studies by Exciton Coupled Circular Dichroism over a Large Distance: Porphyrin Derivatives of Steroids, Dimeric Steroids, and Brevetoxin B⊥ , 1996 .

[42]  K. Nakanishi,et al.  Exciton coupled circular dichroic studies of self-assembled brevetoxin-porphyrin conjugates in lipid bilayers and polar solvents. , 1996, Chemistry & biology.

[43]  K. Nakanishi,et al.  Selective Cation Movement across Lipid Bilayers Containing Brevetoxin B , 1996 .

[44]  K. Nakanishi,et al.  Intramolecular porphyrin pi,pi-stacking: absolute configurational assignment of acyclic compounds with single chiral centers by exciton coupled circular dichroism. , 1996, Enantiomer (Basel. Print).

[45]  Koji Nakanishi,et al.  Ocular Age Pigment "A2-E": An Unprecedented Pyridinium Bisretinoid , 1996 .

[46]  K. Nakanishi,et al.  Structural studies of vinblastine alkaloids by exciton coupled circular dichroism. , 1995, Phytochemistry.

[47]  Koji Nakanishi,et al.  Application of Artificial Pigments to Structure Determination and Study of Photoinduced Transformations of Retinal Proteins , 1995 .

[48]  K. Nakanishi,et al.  Combined synthetic/CD strategy for the preparation and configurational assignments of model acyclic 1,3-polyols with a 1,2-diol terminal. , 1995, Chirality.

[49]  P. Usherwood,et al.  Labeling studies of photolabile philanthotoxins with nicotinic acetylcholine receptors: mode of interaction between toxin and receptor. , 1995, Chemistry & biology.

[50]  K. Nakanishi,et al.  The Location of the Chromophore in Rhodopsin - A Photoaffinity Study , 1994 .

[51]  K. Nakanishi,et al.  Conformational Changes of Rapamycin and Analogs upon Complexing with FKBP Associated with Activity: An Application of Second Derivative CD Spectroscopy , 1994 .

[52]  K. Nakanishi,et al.  Unbleachable rhodopsin with an 11-cis-locked eight-membered ring retinal: the visual transduction process. , 1994, Biochemistry.

[53]  M. Tomasz.  The Mitomycins: Natural Cross-linkers of DNA , 1994 .

[54]  K. Nakanishi,et al.  Circular dichroism exciton chirality method. New red-shifted chromophores for hydroxyl groups , 1993 .

[55]  K. Nakanishi.  Past and present studies with ponasterones, the first insect molting hormones from plants , 1992, Steroids.

[56]  K. Nakanishi,et al.  Photoisomerization of retinal at 13-ene is important for phototaxis of Chlamydomonas reinhardtii: simultaneous measurements of phototactic and photophobic responses. , 1991, Biochemical and biophysical research communications.

[57]  K. Nakanishi,et al.  Unraveling the Chemistry of Tunichrome , 1991 .

[58]  E. MacNichol,et al.  Sensitization of bleached rod photoreceptors by 11-cis-locked analogues of retinal. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[59]  K. Nakanishi,et al.  What is molt-inhibiting hormone? The role of an ecdysteroidogenesis inhibitor in the crustacean molting cycle. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[60]  K. Nakanishi,et al.  Biosynthetic studies of brevetoxins, potent neurotoxins produced by the dinoflagellate Gymnodinium breve , 1989 .

[61]  K. Nakanishi,et al.  Synthesis of mosesin-4, a naturally occurring steroid saponin with shark repellent activity, and its analog 7-β-galactosyl ethyl cholate , 1989 .

[62]  Alain Foucault,et al.  Study of AcOH/HCOOH/H2O/CHCL3 Solvent System Application to the Separation of Two Large and Hydrophobic Fragments of Bacteriorhodopsin Membrane Protein by Centrifugal Partition Chromatography , 1988 .

[63]  P. Usherwood,et al.  Structure and synthesis of a potent glutamate receptor antagonist in wasp venom. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[64]  D. Abraham,et al.  Design, synthesis, and testing of potential antisickling agents. 10. (2,2-Dimethylchroman-6-yl)alkanoic acids. , 1987, Journal of medicinal chemistry.

[65]  K. Nakanishi,et al.  Reaction of acid-activated mitomycin C with calf thymus DNA and model guanines: elucidation of the base-catalyzed degradation of N7-alkylguanine nucleosides. , 1987, Biochemistry.

[66]  K. Nakanishi,et al.  Isolation and structure of a covalent cross-link adduct between mitomycin C and DNA. , 1987, Science.

[67]  K. Tomer,et al.  Structure of brevetoxin A as constructed from NMR and mass spectral data , 1987 .

[68]  K. Nakanishi,et al.  An NMR spectroscopic study of azadirachtin and its trimethyl ether , 1987 .

[69]  K. Nakanishi,et al.  Characterization of Compounds That Induce Symbiosis Between Sea Anemone and Anemone Fish , 1986, Science.

[70]  S. Shimotakahara,et al.  Reaction of DNA with chemically or enzymatically activated mitomycin C: isolation and structure of the major covalent adduct. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[71]  J. Clardy,et al.  Structure of brevetoxin A (GB-1 toxin), the most potent toxin in the Florida red tide organism Gymnodinium breve (Ptychodiscus brevis). , 1986, Journal of the American Chemical Society.

[72]  David J. Williams,et al.  X-ray crystallographic structure determination of detigloyldihydroazadirachtin and reassignment of the structure of the limonoid insect antifeedant azadirachtin , 1986 .

[73]  K. Nakanishi,et al.  Use of differential second-derivative UV and FTIR spectroscopy in structural studies of multichromophoric compounds , 1985 .

[74]  Jun Furukawa,et al.  Isolation and structure of tunichrome B-1, a reducing blood pigment from the tunicate Ascidia nigra (Linnaeus) , 1985 .

[75]  W. Kraus,et al.  The structure of azadirachtin and 22,23-dihydro-23β-methoxyazadirachtin , 1985 .

[76]  K. Nakanishi,et al.  Pavoninins, shark-repelling and ichthyotoxic steroid n-acetylglucosaminides from the defense secretion of the sole pardachirus pavoninus (soleidae) , 1985 .

[77]  Jureepan Saranak,et al.  A rhodopsin is the functional photoreceptor for phototaxis in the unicellular eukaryote Chlamydomonas , 1984, Nature.

[78]  K. Nakanishi,et al.  Applications of Rotation Locular Countercurrent Chromatography in Natural Products Isolation , 1984 .

[79]  K. Nakanishi,et al.  Biosynthetic studies of ipomeamarone , 1984 .

[80]  K. Nakanishi,et al.  Evidence for the necessity of double bond (13-ene) isomerization in the proton pumping of bacteriorhodopsin , 1983 .

[81]  K. Nakanishi,et al.  The absolute configuration of (+)-ipomeamarone , 1983 .

[82]  K. Nakanishi,et al.  A new class of sweet potato phytoalexins , 1983 .

[83]  J. Clardy,et al.  Isolation and structure of brevetoxin B from the "red tide" dinoflagellate Ptychodiscus brevis (Gymnodinium breve) , 1981 .

[84]  K. Nakanishi,et al.  Nonbleachable rhodopsins retaining the full natural chromophore , 1980 .

[85]  K. Nakanishi,et al.  A versatile synthesis of retinoids via condensation of the side-chain to cyclic ketones , 1980 .

[86]  Michael G. Motto,et al.  An external point-charge model for wavelength regulation in visual pigments , 1979 .

[87]  B Honig,et al.  DOUBLE POINT CHARGE MODEL FOR VISUAL PIGMENTS; EVIDENCE FROM DIHYDRORHODOPSINS * , 1979, Photochemistry and photobiology.

[88]  D. Lynn,et al.  Chemical Characterization of a Hormone That Promotes Cell Arrest in G2 in Complex Tissues , 1979, Science.

[89]  K. Nakanishi,et al.  Droplet counter-current chromatography for the preparative isolation of various glycosides , 1979 .

[90]  K. Nakanishi,et al.  Some Terpenoid Insect Antifeedants from Tropical Plants , 1979 .

[91]  K. Nakanishi,et al.  New antisickling agent 3,4-dihydro-2,2-dimethyl-2H-1 benzopyran-6-butyric acid , 1975, Nature.

[92]  K. Nakanishi,et al.  Structure of the insect phagorepellent azadirachtin. Application of PRFT/CWD [partially relaxed Fourier transform/continuous wave decoupling] carbon-13 nuclear magnetic resonance , 1975 .

[93]  K. Nakanishi,et al.  Insect hormones. The structure of ponasterone A, insect-moulting hormone from the leaves of Podocarpus nakaii Hay , 1966 .

[94]  K. Nakanishi,et al.  Structure of pristimerin, a quinonoid triterpene , 1962 .