DOE PAGES title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Total synthesis campaigns toward chlorophylls and related natural hydroporphyrins – diverse macrocycles, unrealized opportunities


Quantitative evaluation of reported routes toward bonellin, chlorophyll a , and tolyporphin A suggests heuristics for practical syntheses of native hydroporphyrins.

ORCiD logo [1]; ORCiD logo [1]; ORCiD logo [1]
  1. Department of Chemistry, North Carolina State University, Raleigh, USA
Publication Date:
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES)
OSTI Identifier:
Grant/Contract Number:  
Resource Type:
Publisher's Accepted Manuscript
Journal Name:
Natural Product Reports
Additional Journal Information:
Journal Name: Natural Product Reports Journal Volume: 35 Journal Issue: 9; Journal ID: ISSN 0265-0568
Royal Society of Chemistry (RSC)
Country of Publication:
United Kingdom

Citation Formats

Liu, Yizhou, Zhang, Shaofei, and Lindsey, Jonathan S. Total synthesis campaigns toward chlorophylls and related natural hydroporphyrins – diverse macrocycles, unrealized opportunities. United Kingdom: N. p., 2018. Web. doi:10.1039/C8NP00020D.
Liu, Yizhou, Zhang, Shaofei, & Lindsey, Jonathan S. Total synthesis campaigns toward chlorophylls and related natural hydroporphyrins – diverse macrocycles, unrealized opportunities. United Kingdom.
Liu, Yizhou, Zhang, Shaofei, and Lindsey, Jonathan S. Mon . "Total synthesis campaigns toward chlorophylls and related natural hydroporphyrins – diverse macrocycles, unrealized opportunities". United Kingdom.
title = {Total synthesis campaigns toward chlorophylls and related natural hydroporphyrins – diverse macrocycles, unrealized opportunities},
author = {Liu, Yizhou and Zhang, Shaofei and Lindsey, Jonathan S.},
abstractNote = {Quantitative evaluation of reported routes toward bonellin, chlorophyll a , and tolyporphin A suggests heuristics for practical syntheses of native hydroporphyrins.},
doi = {10.1039/C8NP00020D},
journal = {Natural Product Reports},
number = 9,
volume = 35,
place = {United Kingdom},
year = {2018},
month = {1}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record

Citation Metrics:
Cited by: 5 works
Citation information provided by
Web of Science

Save / Share:

Works referenced in this record:

Investigation of a Synthesis of meso-Porphyrins Employing High Concentration Conditions and an Electron Transport Chain for Aerobic Oxidation
journal, February 1994

  • Lindsey, Jonathan S.; MacCrum, Kristy A.; Tyhonas, John S.
  • The Journal of Organic Chemistry, Vol. 59, Issue 3
  • DOI: 10.1021/jo00082a014

The total synthesis of chlorophyll a
journal, January 1990

Total synthesis of (±)-bonellin dimethyl ester
journal, January 1983

  • Dutton, Christopher J.; Fookes, Christopher J. R.; Battersby, Alan R.
  • J. Chem. Soc., Chem. Commun., Issue 21
  • DOI: 10.1039/C39830001237

Totalsynthese von (±)-Bonellin-dimethylester
journal, August 1991

The Condensation of Pyrroles with Bromine. A Self-Oxidation and a New Type of Displacement Reaction 1,2
journal, July 1944

  • Corwin, Alsoph H.; Viohl, Paul
  • Journal of the American Chemical Society, Vol. 66, Issue 7
  • DOI: 10.1021/ja01235a026

The structure of bonellin and its derivatives. Unique physiologically active chlorins from the marine echurian Bonellia viridis
journal, January 1980

  • Ballantine, James A.; Psaila, Alexander F.; Pelter, Andrew
  • Journal of the Chemical Society, Perkin Transactions 1
  • DOI: 10.1039/p19800001080

Total Synthesis of the Proposed Structure of (+)-Tolyporphin AO,O-Diacetate
journal, April 1999

Teilsynthese von Methylphäophorbid a und Methylphäophorbid b
journal, January 1937

Partial syntheses of optically pure methyl bacteriopheophorbides c and d from methyl pheophorbide a
journal, May 1980

  • Smith, Kevin M.; Bisset, Graham M. F.; Bushell, Michael J.
  • The Journal of Organic Chemistry, Vol. 45, Issue 11
  • DOI: 10.1021/jo01299a036

Synthetische Arbeiten auf dem Chlorophyllgebiet. Synthese des 2-Desäthyl-phylloporphyrins
journal, July 1952

The Preparation of Benzoylacetic Ester and some of its Homologs
journal, July 1932

  • Dorsch, John B.; McElvain, S. M.
  • Journal of the American Chemical Society, Vol. 54, Issue 7
  • DOI: 10.1021/ja01346a047

De novo synthesis and photophysical characterization of annulated bacteriochlorins. Mimicking and extending the properties of bacteriochlorophylls
journal, January 2011

  • Krayer, Michael; Yang, Eunkyung; Diers, James R.
  • New Journal of Chemistry, Vol. 35, Issue 3, p. 587-601
  • DOI: 10.1039/c0nj00771d

Revised Structure of Tolyporphin A
journal, April 1999

The total synthesis of chlorophyll
journal, January 1961

Novel Synthetic Routes to 8-Vinyl Chlorophyll Derivatives
journal, April 1998

  • Gerlach, Benjamin; Brantley, Sarah E.; Smith, Kevin M.
  • The Journal of Organic Chemistry, Vol. 63, Issue 7
  • DOI: 10.1021/jo9721608

Breakdown of Chlorophyll in Higher Plants-Phyllobilins as Abundant, Yet Hardly Visible Signs of Ripening, Senescence, and Cell Death
journal, February 2016

Hindered diffusion of porphyrins and short-chain polystyrene in small pores
journal, May 1989

  • Kathawalla, Imtiaz A.; Anderson, John L.; Lindsey, Jonathan S.
  • Macromolecules, Vol. 22, Issue 3
  • DOI: 10.1021/ma00193a037

Northern–Southern Route to Synthetic Bacteriochlorins
journal, November 2016

  • Liu, Yizhou; Lindsey, Jonathan S.
  • The Journal of Organic Chemistry, Vol. 81, Issue 23
  • DOI: 10.1021/acs.joc.6b02334

De Novo Synthesis of Stable Tetrahydroporphyrinic Macrocycles:  Bacteriochlorins and a Tetradehydrocorrin
journal, July 2005

  • Kim, Han-Je; Lindsey, Jonathan S.
  • The Journal of Organic Chemistry, Vol. 70, Issue 14
  • DOI: 10.1021/jo050467y

Synthesis and photophysical characteristics of 2,3,12,13-tetraalkylbacteriochlorins
journal, January 2016

  • Zhang, Shaofei; Kim, Han-Je; Tang, Qun
  • New Journal of Chemistry, Vol. 40, Issue 7
  • DOI: 10.1039/C6NJ00517A

Discovery and Synthesis of Less Common Natural Hydroporphyrins
journal, March 1994

  • Montforts, Franz-Peter; Gerlach, Benjamin; Hoeper, Frank
  • Chemical Reviews, Vol. 94, Issue 2
  • DOI: 10.1021/cr00026a003

Totalsynthese des Chlorophylls
journal, September 1960

Modification of the Peripheral Substituents in Chlorophylls a and b and Their Derivatives (Review)
journal, April 2004

Synthesis of chlorins, bacteriochlorins and their tetraaza analogues
journal, July 2016

  • Dudkin, S. V.; Makarova, E. A.; Lukyanets, E. A.
  • Russian Chemical Reviews, Vol. 85, Issue 7
  • DOI: 10.1070/RCR4565

Metrics to ‘green’ chemistry—which are the best?
journal, January 2002

  • Constable, David J. C.; Curzons, Alan D.; Cunningham, Virginia L.
  • Green Chem., Vol. 4, Issue 6
  • DOI: 10.1039/B206169B

Extension of the Eschenmoser sulfide contraction/iminoester cyclization method to the synthesis of tolyporphin chromophore
journal, September 1997

Vibrational Characteristics of Tetrapyrrolic Macrocycles
journal, October 1992

Laser desorption ionisation-time of flight mass spectrometry of the tolyporphins, bioactive metabolites from the cyanobacterium Tolypothrix nodosa
journal, February 2011

  • Prinsep, Michèle R.; Puddick, Jonathan
  • Phytochemical Analysis, Vol. 22, Issue 4
  • DOI: 10.1002/pca.1278

Synthese des Kopro- und Iso-Koproporphyrins
journal, January 1926

Partial synthesis of chlorophyll-a from rhodochlorin
journal, January 1981

Chemical transformations of bacteriochlorophyll a and its medical applications
journal, February 2016

De Novo Synthesis of Gem-Dialkyl Chlorophyll Analogues for Probing and Emulating Our Green World
journal, June 2015

Total Synthesis of (±)-Bonellin Dimethyl Ester
journal, September 1985

  • Montforts, Franz-Peter; Schwartz, Ulrich M.
  • Angewandte Chemie International Edition in English, Vol. 24, Issue 9
  • DOI: 10.1002/anie.198507751

Synthesis of 24 Bacteriochlorin Isotopologues, Each Containing a Symmetrical Pair of 13 C or 15 N Atoms in the Inner Core of the Macrocycle
journal, January 2014

  • Chen, Chih-Yuan; Bocian, David F.; Lindsey, Jonathan S.
  • The Journal of Organic Chemistry, Vol. 79, Issue 3
  • DOI: 10.1021/jo402488n

Chlorophyll a synthesis: A prefatory note
journal, January 1990

Tolyporphin, a novel multidrug resistance reversing agent from the blue-green alga Tolypothrix nodosa
journal, January 1992

  • Prinsep, Michele R.; Caplan, Faith R.; Moore, Richard E.
  • Journal of the American Chemical Society, Vol. 114, Issue 1
  • DOI: 10.1021/ja00027a072

The chemistry of pyrrolic compounds. XIX. Reactions of pyrrolic compounds with orthoformates
journal, January 1972

  • Clezy, Ps; Fookes, Cjr; Liepa, Aj
  • Australian Journal of Chemistry, Vol. 25, Issue 9
  • DOI: 10.1071/CH9721979

Neue Teilsynthesen von Methylphäophorbid a aus Chlorin e6-triester
journal, January 1941

  • Fischer, Hans; Oestreicher, August
  • Justus Liebig's Annalen der Chemie, Vol. 546, Issue 1-2
  • DOI: 10.1002/jlac.19415460105

Photophysical Characterization of the Naturally Occurring Dioxobacteriochlorin Tolyporphin A and Synthetic Oxobacteriochlorin Analogues
journal, July 2017

  • Hood, Don; Niedzwiedzki, Dariusz M.; Zhang, Ran
  • Photochemistry and Photobiology, Vol. 93, Issue 5
  • DOI: 10.1111/php.12781

Synthesis and Structure of Tolyporphin A O,O -Diacetate
journal, October 1999

  • Wang, Wengui; Kishi, Yoshito
  • Organic Letters, Vol. 1, Issue 7
  • DOI: 10.1021/ol9902374

The Total Synthesis of Chlorophyll
journal, July 1960

  • Woodward, R. B.; Ayer, W. A.; Beaton, J. M.
  • Journal of the American Chemical Society, Vol. 82, Issue 14
  • DOI: 10.1021/ja01499a093

The structure and physiological activity of bonellin - a unique chlorin derived from Bonellia viridis
journal, January 1979

  • Agius, L.; Ballantine, J. A.; Ferrito, V.
  • Pure and Applied Chemistry, Vol. 51, Issue 9
  • DOI: 10.1351/pac197951091847

Genome Sequence and Composition of a Tolyporphin-Producing Cyanobacterium-Microbial Community
journal, July 2017

  • Hughes, Rebecca-Ayme; Zhang, Yunlong; Zhang, Ran
  • Applied and Environmental Microbiology, Vol. 83, Issue 19
  • DOI: 10.1128/AEM.01068-17

Recent progress in chlorophyll and porphyrin chemistry
journal, January 1968

Synthesis of the heme d prosthetic group of bacterial terminal oxidase
journal, March 1988

  • Sotiriou, Chariklia.; Chang, C. K.
  • Journal of the American Chemical Society, Vol. 110, Issue 7
  • DOI: 10.1021/ja00215a042

Chlorophyll Modifications and Their Spectral Extension in Oxygenic Photosynthesis
journal, June 2014

β-selective C-glycosidations: lewis-acid mediated reactions of carbohydrates with silyl ketene acetals
journal, September 1997

Carotenoids and related compounds. Part XIV. Stereochemistry and synthesis of geraniol, nerol, farnesol, and phytol
journal, January 1966

  • Burrell, J. W. K.; Garwood, R. F.; Jackman, L. M.
  • Journal of the Chemical Society C: Organic
  • DOI: 10.1039/j39660002144

Rothemund and Adler-Longo reactions revisited: synthesis of tetraphenylporphyrins under equilibrium conditions
journal, March 1987

  • Lindsey, Jonathan S.; Schreiman, Irwin C.; Hsu, Henry C.
  • The Journal of Organic Chemistry, Vol. 52, Issue 5
  • DOI: 10.1021/jo00381a022

The Art and Science of Total Synthesis at the Dawn of the Twenty-First Century
journal, January 2000

Bacteriochlorophyll a and Its Derivatives: Chemistry and Perspectives for Cancer Therapy
journal, August 2008

  • Grin, Mikhail; Mironov, Andrey; Shtil, Alexander
  • Anti-Cancer Agents in Medicinal Chemistry, Vol. 8, Issue 6
  • DOI: 10.2174/187152008785133128

Synthetic studies relevant to biosynthetic research on vitamin B 12 . Part 7. Synthesis of (±)-bonellin dimethyl ester
journal, January 1988

  • Battersby, Alan R.; Dutton, Christopher J.; Fookes, Christopher J. R.
  • J. Chem. Soc., Perkin Trans. 1, Issue 6
  • DOI: 10.1039/P19880001569

Synthetic Chlorins, Possible Surrogates for Chlorophylls, Prepared by Derivatization of Porphyrins
journal, March 2016

Construction of the Bacteriochlorin Macrocycle with Concomitant Nazarov Cyclization To Form the Annulated Isocyclic Ring: Analogues of Bacteriochlorophyll a
journal, February 2017

  • Zhang, Shaofei; Lindsey, Jonathan S.
  • The Journal of Organic Chemistry, Vol. 82, Issue 5
  • DOI: 10.1021/acs.joc.6b02878

A stereocontrolled total synthesis of optically active (R,R)-phytol
journal, January 1981

Synthesis of Orthogonally Protected Pyrrole Tricarboxylic Acid Derivatives: Versatile Building Blocks for Pyrrole-Containing Compounds
journal, January 2006

  • Schmuck, Carsten; Rupprecht, Daniel; Urban, Christian
  • Synthesis, Vol. 2006, Issue 01
  • DOI: 10.1055/s-2005-918435

How green is green chemistry? Chlorophylls as a bioresource from biorefineries and their commercial potential in medicine and photovoltaics
journal, January 2015

  • Ryan, Aoife A.; Senge, Mathias O.
  • Photochemical & Photobiological Sciences, Vol. 14, Issue 4
  • DOI: 10.1039/C4PP00435C

Recent Advances in the Synthesis of Hydroporphyrins
journal, October 2007

Further tolyporphins from the Blue-Green alga Tolypothrix nodosa.
journal, September 1995

Unification of Reaction Metrics for Green Chemistry:  Applications to Reaction Analysis
journal, March 2005

  • Andraos, John
  • Organic Process Research & Development, Vol. 9, Issue 2
  • DOI: 10.1021/op049803n

Synthese des 2.4-Dimethyl-5-carbäthoxy-3-vinyl-pyrrols und seine Überführung in Krypto-pyrrol
journal, December 1925

  • Fischer, Hans; Walach, Bruno
  • Berichte der deutschen chemischen Gesellschaft (A and B Series), Vol. 58, Issue 12
  • DOI: 10.1002/cber.19250581219

Structural Investigations upon a Substituted Dipyrrylmethane. An Unusual Melting Point-Symmetry Relationship 1,2
journal, June 1942

  • Corwin, Alsoph H.; Bailey, William A.; Viohl, Paul
  • Journal of the American Chemical Society, Vol. 64, Issue 6
  • DOI: 10.1021/ja01258a007

Synthesis of Ethyne-Linked or Butadiyne-Linked Porphyrin Arrays Using Mild, Copper-Free, Pd-Mediated Coupling Reactions
journal, August 1995

  • Wagner, Richard W.; Johnson, Thomas E.; Li, Feirong
  • The Journal of Organic Chemistry, Vol. 60, Issue 16
  • DOI: 10.1021/jo00121a052

Total Synthesis of Hematoporphyrin and Protoporphyrin: A Conceptually New Approach
journal, July 2010

  • Martin, Pierre; Mueller, Markus; Flubacher, Dietmar
  • Organic Process Research & Development, Vol. 14, Issue 4
  • DOI: 10.1021/op100036c

Tetrapyrroles: the pigments of life
journal, January 2000

  • Battersby, Alan R.
  • Natural Product Reports, Vol. 17, Issue 6
  • DOI: 10.1039/b002635m

Tolyporphin Macrocycles from the Cyanobacterium Tolypothrix nodosa Selectively Bind Copper and Silver and Reverse Multidrug Resistance
journal, February 2017

A comprehensive review of glycosylated bacterial natural products
journal, January 2015

  • Elshahawi, Sherif I.; Shaaban, Khaled A.; Kharel, Madan K.
  • Chemical Society Reviews, Vol. 44, Issue 21
  • DOI: 10.1039/C4CS00426D

Synthesis of Bacteriochlorins and Their Potential Utility in Photodynamic Therapy (PDT)
journal, August 2004

Synthesis of the enantiomers of 4-substituted γ-lactones with known absolute configuration
journal, January 1978

The Breaking and Mending of meso -Tetraarylporphyrins: Transmuting the Pyrrolic Building Blocks
journal, March 2016

Expanded Scope of Synthetic Bacteriochlorins via Improved Acid Catalysis Conditions and Diverse Dihydrodipyrrin-Acetals
journal, February 2010

  • Krayer, Michael; Ptaszek, Marcin; Kim, Han-Je
  • The Journal of Organic Chemistry, Vol. 75, Issue 4, p. 1016-1039
  • DOI: 10.1021/jo9025572

Spectroscopic and Crystallographic Investigations of Novel BODIPY-Derived Metal–Organic Frameworks
journal, January 2015

  • Li, Ming; Yao, Yi; Ding, Jie
  • Inorganic Chemistry, Vol. 54, Issue 4
  • DOI: 10.1021/ic502219y