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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, 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]


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. 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.

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    $\begingroup$ Those heterocycles are harder than they look... :/ $\endgroup$ – Zhe Nov 6 '18 at 20:31
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Body must be at least 30 characters.

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    $\begingroup$ "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

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