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I shall try to revive this!
A full FAQ post has been written on chemistry.meta.SE, explaining the premise of synthesis golf and the 'rules'. Please take a look at this before answering (if you haven't already).


TAK-457 is a drug (more accurately, a prodrug) that displays antifungal activity:[1,2]

Structure of TAK-457

Some rules, as usual:

  • At most one chiral centre may be bought in your starting material(s). [Chiral catalysts, ligands, auxiliaries, etc. do not fall under this rule.]

  • Your synthesis must feature a method for construction of either the triazole or tetrazole ring (i.e. do not buy both).

  • The counterion doesn't matter.

  • Bonus points for synthesis that can be adapted to produce the other three stereoisomers of the drug (preferably via late stage diversification as opposed to, say, using a different enantiomer of starting material). These stereoisomers were of interest.[3]


References

  1. Ichikawa, T.; Kitazaki, T.; Matsushita, Y.; Yamada, M.; Hayashi, R.; Yamaguchi, M.; Kiyota, Y.; Okonogi, K.; Itoh, K. Optically Active Antifungal Azoles. XII. Synthesis and Antifungal Activity of the Water-Soluble Prodrugs of 1-[(1​R,2​R)-2-(2,4-Difluorophenyl)-2-hydroxy-1-methyl-3-(1​H-1,2,4-triazol-1-yl)propyl]-3-[4-(1​H-1-tetrazolyl)phenyl]-2-imidazolidinone. Chem. Pharm. Bull. 2001, 49 (9), 1102–1109. DOI: 10.1248/cpb.49.1102.

  2. Hayashi, R.; Kitamoto, N.; Iizawa, Y.; Ichikawa, T.; Itoh, K.; Kitazaki, T.; Okonogi, K. Efficacy of TAK-457, a novel intravenous triazole, against invasive pulmonary aspergillosis in neutropenic mice. Antimicrob. Agents Chemother. 2002, 46 (2), 283–287. DOI: 10.1128/AAC.46.2.283-287.2002.

  3. Ichikawa, T.; Yamada, M.; Yamaguchi, M.; Kitazaki, T.; Matsushita, Y.; Higashikawa, K.; Itoh, K. Optically Active Antifungal Azoles. XIII. Synthesis of Stereoisomers and Metabolites of 1-[(1​R,2​R)-2-(2,4-difluorophenyl)-2-hydroxy-1-methyl-3-(1​H-1,2,4-triazol-1-yl)propyl]-3-[4-(1​H-1-tetrazolyl)phenyl]-2-imidazolidinone (TAK-456). Chem. Pharm. Bull. 2001, 49 (9), 1110–1119. DOI: 10.1248/cpb.49.1110.

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  • 2
    $\begingroup$ I was wondering if Synthesis Golf would make a comeback. Great to see! $\endgroup$ – A.K. Oct 27 '18 at 17:58
  • 3
    $\begingroup$ @A.K., I've been meaning to post one for ages, but never quite got round to it - until today! $\endgroup$ – orthocresol Oct 27 '18 at 18:29
  • 1
    $\begingroup$ Those heterocycles are harder than they look... :/ $\endgroup$ – Zhe Nov 6 '18 at 20:31

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