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, an injectable prodrug of TAK-456) that displays antifungal activity:[1,2,3]

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.[4]


  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. Tsuchimori, N.; Hayashi, R.; Kitamoto, N.; Asai, K.; Kitazaki, T.; Iizawa, Y.; Itoh, K.; Okonogi, K. In Vitro and In Vivo Antifungal Activities of TAK-456, a Novel Oral Triazole with a Broad Antifungal Spectrum. Antimicrob. Agents Chemother. 2002, 46 (5), 1388-1393. DOI: 10.1128/AAC.46.5.1388-1393.2002.

  4. 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.

  • 2
    $\begingroup$ Those heterocycles are harder than they look... :/ $\endgroup$ – Zhe Nov 6 '18 at 20:31

enter image description here

enter image description here

Body must be at least 30 characters.

|improve this answer|||||
  • 1
    $\begingroup$ "Body must be at least 30 characters." Yes, and shoes should be tied. Please clean up your answer, as it stands it's not suitable for prime-time. $\endgroup$ – Todd Minehardt Dec 20 '19 at 0:56
  • $\begingroup$ @ToddMinehardt I am sorry the answer is not typed up. I have not had time to type it up and since I left university this year, I do not have access to ChemDraw. Please let me know if any of the reactions are not clear and I will try to elaborate. $\endgroup$ – Laksh Dec 25 '19 at 16:06

Your Answer

By clicking “Post Your Answer”, you agree to our terms of service, privacy policy and cookie policy

Not the answer you're looking for? Browse other questions tagged or ask your own question.