Total Synthesis of Myceliothermophins C, D, and E

Abstract

The total synthesis of cytotoxic polyketides myceliothermophins E (1), C (2) and D (3) through a cascade-based cyclization to form the trans-fused decalin system is described. The convergent synthesis delivered all three natural products through late-stage divergence and facilitated unambiguous C21 structural assignments for 2 and 3 through X-ray crystallographic analysis which revealed an interesting dimeric structure between its enantiomeric forms.

Total Synthesis and Structural Revision of Antibiotic CJ‐16,264

“…Isolated from fungus CL39457, antibiotic CJ‐16,2641 ( 1 , Figure 1 A) was reported to exhibit impressive activities against drug‐resistant Gram‐positive bacteria such as Staphylococcus aureus 01A1120 (MIC=0.78 μg mL −1 ) and Gram‐negative bacteria such as Moraxella catarrhalis 87A1055 (MIC=0.39 μg mL −1 ) and Escherichia coli 51A1051 with altered permeability (MIC=6.25 μg mL −1 ). The assigned structure of this molecule is intriguing in that it is amongst the most complex of its relatives, CJ‐16,367 [ 2 , Figure 1 A, stereochemistry unassigned, isolated from the same fungus (CL39457)],1 UCS1025A ( 3 , Figure 1 A)2 and UCS1025B ( 4 , Figure 1 A),2 21‐( S )‐ and 21‐( R )‐myceliothermophins C ( 5 a )3, 4 and D ( 5 b )3, 4 (Figure 1 B), and the most recently reported antibiotic pyrrolizilactone5 ( 1 a , Figure 1 A). Antibiotic CJ‐16,264 ( 1 ) possesses a challenging tetramethylated decalin system, whose relative and absolute configurations differ from those of its less complex siblings UCS compounds ( 3 and 4 ), and the myceliothermophins C ( 5 a ) and D ( 5 b ) (see Figure 1).…”

Total Synthesis and Structural Revision of Antibiotic CJ‐16,264

“…Isolated from fungus CL39457, antibiotic CJ-16,264 [1] (1, Figure 1A)w as reported to exhibit impressive activities against drug-resistant Gram-positive bacteria such as Staphylococcus aureus 01A1120 (MIC = 0.78 mgmL À1 )a nd Gramnegative bacteria such as Moraxella catarrhalis 87A1055 (MIC = 0.39 mgmL À1 )a nd Escherichia coli 51A1051 with altered permeability (MIC = 6.25 mgmL À1 ). Thea ssigned structure of this molecule is intriguing in that it is amongst the most complex of its relatives,C J-16,367 [2,F igure 1A, stereochemistry unassigned, isolated from the same fungus (CL39457)], [1] UCS1025A (3,F igure 1A) [2] and UCS1025B (4,F igure 1A), [2] 21-(S)-and 21-(R)-myceliothermophins C (5a) [3,4] and D( 5b) [3,4] (Figure 1B), and the most recently reported antibiotic pyrrolizilactone [5] (1a,F igure 1A). Antibiotic CJ-16,264 (1)p ossesses ac hallenging tetramethylated decalin system, whose relative and absolute configurations differ from those of its less complex siblings UCS compounds (3 and 4), and the myceliothermophins C(5a)and D(5b)(see Figure 1).…”

New Members of the Deutsche Akademie der Naturforscher Leopoldina / Teacher of the Year at SCIENCE Award: Stephan P. A. Sauer / Scientist of the Year Prize, University of Frankfurt: H. Schwalbe / Lorenz Oken Medal: H.‐J. Quadbeck‐Seeger / Normann Medal: U. T. Bornscheuer / Wöhler–BASF Early‐Career Prize: M. Walter / Eni Award for New Frontiers in Hydrocarbons: A. H. Hoveyda / Nemitsas Prize and Einstein Professorship: K. C. Nicolaou

“…Nicolaou, who was featured here when he was made a Foreign Associate of The Royal Society,11a was also recently awarded the 2014 Einstein Professorship by the Chinese Academy of Sciences. His most recent contribution to Angewandte Chemie is a report on the total synthesis of myceliothermophins C, D, and E 11b. Nicolaou is on the Editorial or Advisory Boards of Chemistry—A European Journal , Chemistry—An Asian Journal , ChemistryOpen , and the Israel Journal of Chemistry…”