title: Total synthesis and biological evaluation of the tetramic acid based natural product harzianic acid and its stereoisomers.
abstract: The bioactive natural product harzianic acid was prepared for the first time in just six steps (longest linear sequence) with an overall yield of 22%. The identification of conditions to telescope amide bond formation and a Lacey-Dieckmann reaction into one pot proved important. The three stereoisomers of harzianic acid were also prepared, providing material for comparison of their biological activity. While all of the isomers promoted root growth, improved antifungal activity was unexpectedly associated with isomers in the enantiomeric series opposite that of harzianic acid.
authors: School of Chemistry and Biomedical Sciences Research Complex, University of St. Andrews and EaStCHEM , North Haugh, St. Andrews, Fife KY169ST, U.K.
authors: Alan R
authors: AR
authors: Healy
authors: Francesco
authors: F
authors: Vinale
authors: Matteo
authors: M
authors: Lorito
authors: Nicholas J
authors: NJ
authors: Westwood
mesh_terms: D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001688:Biological Products / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006885:Hydroxybutyrates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D011758:Pyrroles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011760:Pyrrolidinones / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D000935:Antifungal Agents; D001688:Biological Products; D006885:Hydroxybutyrates; D011758:Pyrroles; D011760:Pyrrolidinones; C088506:harzianic acid; C009435:tetramic acid
references: FEMS Microbiol Lett. 2013 Oct;347(2):123-9
references: 23909277
references: J Antibiot (Tokyo). 1994 Jun;47(6):731-2
references: 8040080
references: J Antibiot (Tokyo). 2007 Aug;60(8):524-8
references: 17827664
references: Nat Prod Rep. 2010 May;27(5):637-57
references: 20376388
references: Naturwissenschaften. 2007 Jan;94(1):1-11
references: 16944091
references: Angew Chem Int Ed Engl. 2015 Mar 23;54(13):4046-50
references: 25650886
references: J Nat Prod. 2006 Jul;69(7):1025-8
references: 16872138
references: J Biol Chem. 1995 Nov 10;270(45):26723-6
references: 7592901
references: J Biomol Screen. 2009 Sep;14(8):970-9
references: 19641222
references: J Antibiot (Tokyo). 2004 Mar;57(3):235-7
references: 15152810
references: Molecules. 2014 Jul 08;19(7):9760-72
references: 25006784
references: J Nat Prod. 2009 Nov;72(11):2032-5
references: 19894739
references: Phytomedicine. 2012 May 15;19(7):609-17
references: 22397996
references: J Nat Prod. 2010 Apr 23;73(4):628-31
references: 20180542
references: Org Lett. 2000 Nov 16;2(23):3611-3
references: 11073657
references: Annu Rev Phytopathol. 2010;48:395-417
references: 20455700