Revisitation of the Preparation of ( S, S)‐2,8‐Diazabicyclo[4.3.0]nonane Through Enzymatic Resolution.

• Published in: ChemistrySelect
• Main Authors: Dalsaniya, Sagar Chandrakant, Bharati, Alika, Sudhakar, Yogeswari, Khomane, Navnath, Gurrala, Sheelu, Ghosh, Subhash, Kumaraguru, Thenkrishnan
• Format: Article in Journal/Newspaper
• Language: English
• Published: Wiley 2023
• Subjects: Antarc*; Antarctica
• Online Access: http://dx.doi.org/10.1002/slct.202301745

Abstract A chemo‐enzymatic route for the preparation of ( S , S )‐2,8‐diazabicyclo[4.3.0]nonane, a key chiral intermediate of Moxifloxacin, has been evaluated and improved. The activity of immobilized Candida antarctica lipase B was found to be increased four times for the selective hydrolysis of cis ‐dimethyl 1‐acetylpiperidine‐2,3‐dicarboxylate at 50 °C as compared to 27 °C. The reaction has an optimum temperature of 50–60 °C and an optimum pH of 7.5. The reaction follows typical Michaelis‐Menten kinetics with V max,obsd =2472 units/g, K m,obsd =0.334 M, n=6, correlation coeff. r=0.995 at 50 °C. The reaction time and enzyme loading were reduced to 26 h at 15 % (w/w) as compared to 14 days at 50 % (w/w) loading. The enzyme was found to be recyclable up to 5 times. Further, the reduction of dimethyl pyridine‐2,3‐dicarboxylate was performed at a temperature of 27 °C under an H 2 ‐filled balloon, in the presence of Pd/C and acetic acid, under atmospheric pressure to give cis ‐(±)‐Dimethylpiperidine‐2,3‐dicarboxylate. We anticipate that our results will be beneficial to the pharmaceutical industry for the large‐scale production of ( S , S )‐2,8‐diazabicyclo[4.3.0]nonane.